Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.

PubMed

Kastelein, John J P; Maki, Kevin C; Susekov, Andrey; Ezhov, Marat; Nordestgaard, Borge G; Machielse, Ben N; Kling, Douglas; Davidson, Michael H

2014-01-01

Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms. The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid. This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet. Fasting serum TGs changed from baseline by -25.9% (P < .01 vs OO), -25.5% (P < .01 vs OO), and -30.9% (P < .001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with -4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDL-C ratio, very low-density lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase A2, and arachidonic acid were significantly lowered (P < .05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P < .001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P < .05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO. OM3-FFA achieved the primary end point for TG lowering and secondary end point of non-HDL-C lowering at 2, 3, and 4 g/d in persons with severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Measurement of the alpha4beta2* nicotinic acetylcholine receptor ligand 2-[(18)F]Fluoro-A-85380 and its metabolites in human blood during PET investigation: a methodological study.

PubMed

Sorger, Dietlind; Becker, Georg A; Patt, Marianne; Schildan, Andreas; Grossmann, Udo; Schliebs, Reinhard; Seese, Anita; Kendziorra, Kai; Kluge, Magnus; Brust, Peter; Mukhin, Alexey G; Sabri, Osama

2007-04-01

2-[(18)F]fluoro-A-85380 (2-[(18)F]FA) is a new radioligand for noninvasive imaging of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET) in human brain. In most cases, quantification of 2-[(18)F]FA receptor binding involves measurement of free nonmetabolized radioligand concentration in blood. This requires an efficient and reliable method to separate radioactive metabolites from the parent compound. In the present study, three analytical methods, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) have been tested. Reversed-phase TLC of deproteinized aqueous samples of plasma provides good estimates of 2-[(18)F]FA and its metabolites. However, because of the decreased radioactivity in plasma samples, this method can be used in humans over the first 2 h after radioligand injection only. Reliable quantification of the parent radioligand and its main metabolites was obtained using reversed-phase HPLC, followed by counting of eluted fractions in a well gamma counter. Three main and five minor metabolites of 2-[(18)F]FA were detected in human blood using this method. On average, the unchanged 2-[(18)F]FA fraction in plasma of healthy volunteers measured at 14, 60, 120, 240 and 420 min after radioligand injection was 87.3+/-2.2%, 74.4+/-3%, 68.8+/-5%, 62.3+/-8% and 61.0+/-8%, respectively. In patients with neurodegenerative disorders, the values corresponding to the three last time points were significantly lower. The fraction of nonmetabolized 2-[(18)F]FA in plasma determined using SPE did not differ significantly from that obtained by HPLC (+gamma counting) (n=73, r=.95). Since SPE is less time-consuming than HPLC and provides comparable results, we conclude that SPE appears to be the most suitable method for measurement of 2-[(18)F]FA parent fraction during PET investigations.

Metabolic effects of cortisol, ACTH, adrenalin and insulin in the marsupial sugar glider, Petaurus breviceps.

PubMed

Bradley, A J; Stoddart, D M

1990-11-01

The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals but contrast with the pattern described for two macropodid marsupials, the red kangaroo Macropus rufus and the quokka Setonix brachyurus.

Fatty acid kinetic responses to running above or below lactate threshold.

PubMed

Kanaley, J A; Mottram, C D; Scanlon, P D; Jensen, M D

1995-08-01

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1-14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects

PubMed Central

Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; DeFronzo, Ralph A; Dubé, John J; Musi, Nicolas

2013-01-01

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IκBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IκBα protein (an indication of decreased IκB kinase–nuclear factor κB signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs. PMID:23529132

Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

PubMed

Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

2013-06-01

Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus.

PubMed

Xiang, Yu-luan; He, Li; Xiao, Jun; Xia, Shuang; Deng, Song-bai; Xiu, Yun; She, Qiang

2012-03-01

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM + TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg-1·day-1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

PubMed

Nagase, Midori; Yamamoto, Yorihiro; Miyazaki, Yusuke; Yoshino, Hiide

2016-05-01

Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

PubMed

Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

2013-09-05

Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics.

PubMed

Fuller, Miles; Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T

2016-01-01

During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance.

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects

PubMed Central

Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J.; Musi, Nicolas

2018-01-01

Objective The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Research design and methods Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. Results The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. Conclusions In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals. PMID:29649324

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

PubMed

Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

2018-01-01

The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

PubMed Central

Stein, D T; Stevenson, B E; Chester, M W; Basit, M; Daniels, M B; Turley, S D; McGarry, J D

1997-01-01

Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics. PMID:9218517

Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart

PubMed Central

Kjekshus, John K.; Mjøs, Ole D.

1972-01-01

Since elevation of plasma concentrations of free fatty acids (FFA) increases myocardial oxygen consumption without influencing mechanical performance in normal hearts, it was the purpose of this study to determine whether FFA would modify mechanical performance at limited oxygen supply. Left coronary blood flow was reduced by gradual clamping of a shunt from the left carotid artery until moderate ventricular dilatation supervened. Left ventricular systolic pressure (LVSP), its maximal rate of rise (dP/dt) and stroke volume (SV) were unchanged or slightly reduced. The ischemia resulted in a decrease in myocardial oxygen consumption (MVO2) from 9.7±1.1 ml/min to 7.9±0.8 ml/min, and myocardial lactate uptake was reduced or reversed to excretion. Increasing the plasma concentrations of FFA from 359±47 μEq/1 to 3688±520 μEq/1 by intravenous infusion of a triglyceride emulsion and heparin resulted in further ventricular dilatation, accompanied by increased excretion of lactate. The ventricular decompensation and enhancement of anaerobic myocardial metabolism associated with increased uptake of FFA was not related to changes in coronary flow, MVO2, or LVSP. dP/dt and SV were virtually unchanged. Intravenous infusion of glucose/insulin, which lowered plasma concentrations of FFA, reversed ventricular dilatation and lactate excretion. The data support the hypothesis that high concentrations of FFA play a significant role in increasing myocardial oxygen requirement and thereby promote depression of contractility of the hypoxic heart in experimental animals. Images PMID:5032525

Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy.

PubMed

Zhang, Fuyang; Zhao, Shihao; Yan, Wenjun; Xia, Yunlong; Chen, Xiyao; Wang, Wei; Zhang, Jinglong; Gao, Chao; Peng, Cheng; Yan, Feng; Zhao, Huishou; Lian, Kun; Lee, Yan; Zhang, Ling; Lau, Wayne Bond; Ma, Xinliang; Tao, Ling

2016-11-01

The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte. Copyright © 2016. Published by Elsevier B.V.

The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice.

PubMed

Moon, Morgan L; Joesting, Jennifer J; Lawson, Marcus A; Chiu, Gabriel S; Blevins, Neil A; Kwakwa, Kristin A; Freund, Gregory G

2014-09-01

Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that last beyond an acute elevation in plasma FFAs. Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 h after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hours after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24h after palmitic acid treatment. Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

PubMed Central

Solomon, Thomas P. J.; Haus, Jacob M.; Marchetti, Christine M.; Stanley, William C.; Kirwan, John P.

2009-01-01

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFAox) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; −598 ± 125 kcal/day, 66 ± 1 yr, 32.8 ± 1.8 kg/m2) or a eucaloric (n = 8; 67 ± 2 yr, 35.3 ± 2.1 kg/m2) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-14C]palmitate) were assessed throughout a 7-h, 40 mU·m−2·min−1 hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (−7.7 ± 0.5 vs. −3.3 ± 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 ± 261 vs. 1,764 ± 194 μmol/l, P < 0.05) and FFA turnover (3.20 ± 0.58 vs. 2.19 ± 0.58 μmol·kg FFM−1·min−1, P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFAox was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFAox (12.3 ± 7.7 and 14.7 ± 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization. PMID:19531640

Rapid measurement of plasma free fatty acid concentration and isotopic enrichment using LC/MS

PubMed Central

Persson, Xuan-Mai T.; Błachnio-Zabielska, Agnieszka Urszula; Jensen, Michael D.

2010-01-01

Measurements of plasma free fatty acids (FFA) concentration and isotopic enrichment are commonly used to evaluate FFA metabolism. Until now, gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) was the best method to measure isotopic enrichment in the methyl derivatives of 13C-labeled fatty acids. Although IRMS is excellent for analyzing enrichment, it requires time-consuming derivatization steps and is not optimal for measuring FFA concentrations. We developed a new, rapid, and reliable method for simultaneous quantification of 13C-labeled fatty acids in plasma using high-performance liquid chromatography-mass spectrometry (HPLC/MS). This method involves a very quick Dole extraction procedure and direct injection of the samples on the HPLC system. After chromatographic separation, the samples are directed to the mass spectrometer for electrospray ionization (ESI) and analysis in the negative mode using single ion monitoring. By employing equipment with two columns connected parallel to a mass spectrometer, we can double the throughput to the mass spectrometer, reducing the analysis time per sample to 5 min. Palmitate flux measured using this approach agreed well with the GC/C/IRMS method. This HPLC/MS method provides accurate and precise measures of FFA concentration and enrichment. PMID:20526002

Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo.

PubMed

Pereira, Sandra; Park, Edward; Moore, Jessy; Faubert, Brandon; Breen, Danna M; Oprescu, Andrei I; Nahle, Ashraf; Kwan, Denise; Giacca, Adria; Tsiani, Evangelia

2015-11-01

Elevated levels of plasma free fatty acids (FFA), which are commonly found in obesity, induce insulin resistance. FFA activate protein kinases including the proinflammatory IκBα kinase β (IKKβ), leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and impaired insulin signaling. To test whether resveratrol, a polyphenol found in red wine, prevents FFA-induced insulin resistance, we used a hyperinsulinemic-euglycemic clamp with a tracer to assess hepatic and peripheral insulin sensitivity in overnight-fasted Wistar rats infused for 7 h with saline, Intralipid plus 20 U·mL(-1) heparin (IH; triglyceride emulsion that elevates FFA levels in vivo; 5.5 μL·min(-1)) with or without resveratrol (3 mg·kg(-1)·h(-1)), or resveratrol alone. Infusion of IH significantly decreased glucose infusion rate (GIR; P < 0.05) and peripheral glucose utilization (P < 0.05) and increased endogenous glucose production (EGP; P < 0.05) during the clamp compared with saline infusion. Resveratrol co-infusion, however, completely prevented the effects induced by IH infusion: it prevented the decreases in GIR (P < 0.05 vs. IH), peripheral glucose utilization (P < 0.05 vs. IH), and insulin-induced suppression of EGP (P < 0.05 vs. IH). Resveratrol alone had no effect. Furthermore, IH infusion increased serine (307) phosphorylation of IRS-1 in soleus muscle (∼30-fold, P < 0.001), decreased total IRS-1 levels, and decreased IκBα content, consistent with activation of IKKβ. Importantly, all of these effects were abolished by resveratrol (P < 0.05 vs. IH). These results suggest that resveratrol prevents FFA-induced hepatic and peripheral insulin resistance and, therefore, may help mitigate the health consequences of obesity.

Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

PubMed

Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

2012-09-01

We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

Anti-diabetic effects of DA-11004, a synthetic IDPc inhibitor in high fat high sucrose diet-fed C57BL/6J mice.

PubMed

Shin, Chang Yell; Jung, Mi Young; Lee, In Ki; Son, Miwon; Kim, Dong Sung; Lim, Joong In; Kim, Soon Hoe; Yoo, Moohi; Huh, Tae Lin; Sohn, Young Taek; Kim, Won Bae

2004-01-01

DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study.

PubMed

Tabara, Yasuharu; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Gotoh, Norimoto; Terao, Chikashi; Yamada, Ryo; Kosugi, Shinji; Sekine, Akihiro; Nakayama, Takeo; Matsuda, Fumihiko

2016-01-01

Previous studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic β-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia. A total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. As serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (≥12 h, P<0.001) or near-fasting (5-11 h, P<0.001) conditions, and not in those taken under non-fasting (<5 h, P=0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (β=0.052, P<0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA(⁎)glucose; β=0.036, P<0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300 cm/s. Physiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature. Copyright © 2016 Elsevier Inc. All rights reserved.

A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats.

PubMed

Stanimirovic, Julijana; Obradovic, Milan; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Pitt, Samantha J; Stewart, Alan J; Isenovic, Esma R

2016-04-01

Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. Copyright © 2016 Elsevier Inc. All rights reserved.

The Production of Nitric Oxide, IL-6, and TNF-Alpha in Palmitate-Stimulated PBMNCs Is Enhanced through Hyperglycemia in Diabetes

PubMed Central

Volpe, Caroline Maria Oliveira; Abreu, Luana Farnese Machado; Gomes, Pollyanna Stephanie; Gonzaga, Raquel Miranda; Veloso, Clara Araújo; Nogueira-Machado, José Augusto

2014-01-01

We examined nitric oxide (NO), IL-6, and TNF-α secretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD) patients or nondiabetic (ND) controls. Free fatty acids (FFA) have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-α, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC) or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbates in vitro inflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate). These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion under in vitro FFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications. PMID:24803982

Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid- and lipopolysaccharide-induced TLR4 signalling.

PubMed

Reichardt, François; Chassaing, Benoit; Nezami, Behtash Ghazi; Li, Ge; Tabatabavakili, Sahar; Mwangi, Simon; Uppal, Karan; Liang, Bill; Vijay-Kumar, Matam; Jones, Dean; Gewirtz, Andrew T; Srinivasan, Shanthi

2017-03-01

A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility. The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight without blood glucose alteration. Dysbiosis was exhibited after 6 weeks of feeding, as reflected by increased fecal LPS and bacterial metabolites and concomitant higher plasma FFA. The numbers of nitrergic myenteric neurons were reduced in the proximal colon after 9 and 12 weeks of WD and this was also associated with delayed colonic transit. WD-fed Toll-like receptor 4 (TLR4) -/- mice did not exhibit myenteric cell loss or dysmotility. Finally, LPS (0.5-2 ng·ml -1 ) and palmitate (20 and 30 μm) acted synergistically to induce neuronal cell death in vitro, which was prevented by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. In conclusion, WD-feeding results in increased levels of FFA and microbiota that, even in absence of hyperglycaemia or overt endotoxaemia, synergistically induce TLR4-mediated neurodegeneration and dysmotility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.

PubMed

Pasman, Wilrike J; Heimerikx, Jos; Rubingh, Carina M; van den Berg, Robin; O'Shea, Marianne; Gambelli, Luisa; Hendriks, Henk F J; Einerhand, Alexandra W C; Scott, Corey; Keizer, Hiskias G; Mennen, Louise I

2008-03-20

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 muM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day.CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake.

Update on the management of severe hypertriglyceridemia--focus on free fatty acid forms of omega-3.

PubMed

Pirillo, Angela; Catapano, Alberico Luigi

2015-01-01

High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases, often associated with anomalies in other lipids or lipoproteins. Hypertriglyceridemia (HTG), particularly at very high levels, significantly increases also the risk of acute pancreatitis. Thus, interventions to lower TG levels are required to reduce the risk of pancreatitis and cardiovascular disease. Several strategies may be adopted for TG reduction, including lifestyle changes and pharmacological interventions. Among the available drugs, the most commonly used for HTG are fibrates, nicotinic acid, and omega-3 polyunsaturated fatty acids (usually a mixture of eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA). These last are available under different concentrated formulations containing high amounts of omega-3 fatty acids, including a mixture of EPA and DHA or pure EPA. The most recent formulation contains a free fatty acid (FFA) form of EPA and DHA, and exhibits a significantly higher bioavailability compared with the ethyl ester forms contained in the other formulations. This is due to the fact that the ethyl ester forms, to be absorbed, need to be hydrolyzed by the pancreatic enzymes that are secreted in response to fat intake, while the FFA do not. This higher bioavailability translates into a higher TG-lowering efficacy compared with the ethyl ester forms at equivalent doses. Omega-3 FFA are effective in reducing TG levels and other lipids in hypertriglyceridemic patients as well as in high cardiovascular risk patients treated with statins and residual HTG. Currently, omega-3 FFA formulation is under evaluation to establish whether, in high cardiovascular risk subjects, the addition of omega-3 to statin therapy may prevent or reduce major cardiovascular events.

The Pharmacokinetic Profile of a New Gastroresistant Capsule Preparation of Eicosapentaenoic Acid as the Free Fatty Acid

PubMed Central

Scaioli, Eleonora; Munarini, Alessandra; Hull, Mark A.; Belluzzi, Andrea

2015-01-01

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohn's disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10–16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the “universal donor” with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance. PMID:26339608

Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.

PubMed

Bailin, Samuel S; Jenkins, Cathy A; Petucci, Christopher; Culver, Jeffrey A; Shepherd, Bryan E; Fessel, Joshua P; Hulgan, Todd; Koethe, John R

2018-05-02

In human immunodeficiency virus (HIV)-negative individuals, a plasma metabolite profile, characterized by higher levels of branched-chain amino acids (BCAA), aromatic amino acids, and C3/C5 acylcarnitines, is associated with insulin resistance and increased risk of diabetes. We sought to characterize the metabolite profile accompanying insulin resistance in HIV-positive persons to assess whether the same or different bioenergetics pathways might be implicated. We performed an observational cohort study of 70 nondiabetic, HIV-positive individuals (50% with body mass index ≥30 kg/m 2 ) on efavirenz, tenofovir, and emtricitabine with suppressed HIV-1 RNA levels (<50 copies/mL) for at least 2 years and a CD4 + count over 350 cells/μL. We measured fasting insulin resistance using the homeostatic model assessment 2, plasma free fatty acids (FFA) using gas chromatography, and amino acids, acylcarnitines, and organic acids using liquid chromatography/mass spectrometry. We assessed the relationship of plasma metabolites with insulin resistance using multivariable linear regression. The median age was 45 years, median CD4 + count was 701 cells/μL, and median hemoglobin A1c was 5.2%. Insulin resistance was associated with higher plasma C3 acylcarnitines (p = .01), but not BCAA or C5 acylcarnitines. However, insulin resistance was associated with lower plasma levels of C18, C16, C12, and C2 acylcarnitines (p ≤ .03 for all), and lower C18 and C16 acylcarnitine:FFA ratios (p = .002, and p = .03, respectively). In HIV-positive persons, lower levels of plasma acylcarnitines, including the C2 product of complete fatty acid oxidation, are a more prominent feature of insulin resistance than changes in BCAA, suggesting impaired fatty acid uptake and/or mitochondrial oxidation is a central aspect of glucose intolerance in this population.

Peroxisome Proliferator-Activated Receptor β/δ (PPARβ/δ) but Not PPARα Serves as a Plasma Free Fatty Acid Sensor in Liver ▿ †

PubMed Central

Sanderson, Linda M.; Degenhardt, Tatjana; Koppen, Arjen; Kalkhoven, Eric; Desvergne, Beatrice; Müller, Michael; Kersten, Sander

2009-01-01

Peroxisome proliferator-activated receptor α (PPARα) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARα target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARα, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARβ/δ during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARα. Binding of PPARβ/δ to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARβ/δ by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARβ/δ. In contrast, the data did not support activation of PPARα by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARβ/δ target genes and show that upregulation of gene expression by PPARβ/δ is sensitive to plasma FFA levels. In contrast, this is not the case for PPARα, revealing a novel mechanism for functional differentiation between PPARs. PMID:19805517

Downstream Processing of Synechocystis for Biofuel Production

NASA Astrophysics Data System (ADS)

Sheng, Jie

Lipids and free fatty acids (FFA) from cyanobacterium Synechocystis can be used for biofuel (e.g. biodiesel or renewable diesel) production. In order to utilize and scale up this technique, downstream processes including culturing and harvest, cell disruption, and extraction were studied. Several solvents/solvent systems were screened for lipid extraction from Synechocystis. Chloroform + methanol-based Folch and Bligh & Dyer methods were proved to be "gold standard" for small-scale analysis due to their highest lipid recoveries that were confirmed by their penetration of the cell membranes, higher polarity, and stronger interaction with hydrogen bonds. Less toxic solvents, such as methanol and MTBE, or direct transesterification of biomass (without preextraction step) gave only slightly lower lipid-extraction yields and can be considered for large-scale application. Sustained exposure to high and low temperature extremes severely lowered the biomass and lipid productivity. Temperature stress also triggered changes of lipid quality such as the degree of unsaturation; thus, it affected the productivities and quality of Synechocystis-derived biofuel. Pulsed electric field (PEF) was evaluated for cell disruption prior to lipid extraction. A treatment intensity > 35 kWh/m3 caused significant damage to the plasma membrane, cell wall, and thylakoid membrane, and it even led to complete disruption of some cells into fragments. Treatment by PEF enhanced the potential for the low-toxicity solvent isopropanol to access lipid molecules during subsequent solvent extraction, leading to lower usage of isopropanol for the same extraction efficiency. Other cell-disruption methods also were tested. Distinct disruption effects to the cell envelope, plasma membrane, and thylakoid membranes were observed that were related to extraction efficiency. Microwave and ultrasound had significant enhancement of lipid extraction. Autoclaving, ultrasound, and French press caused significant release of lipid into the medium, which may increase solvent usage and make medium recycling difficult. Production of excreted FFA by mutant Synechocystis has the potential of reducing the complexity of downstream processing. Major problems, such as FFA precipitation and biodegradation by scavengers, account for FFA loss in operation. Even a low concentration of FFA scavengers could consume FFA at a high rate that outpaced FFA production rate. Potential strategies to overcome FFA loss include high pH, adsorptive resin, and sterilization techniques.

[Effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats].

PubMed

Yu, Tao; Liu, Rui; Li, Mao; Li, Xian; Qiang, Ou; Huang, Wei; Tang, Chengwei

2014-03-01

To investigate effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats. SD rats were divided into control group (n = 14) and high-fat diet group (n = 36). Obese rats from the high-fat diet group were further divided into 2 groups: the obese group (n = 14) and the octreotide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h (40 mg/kg BW) for 8 days. Body weight, fasting plasma glucose (FPG), fasting serum insulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) levels, pancreatic TG and FFA content were measured. Homeostatic model assessment (HOMA) index was calculated. Somatostatin (SST) and the expression of adipose differentiation-related protein (ADFP) in pancrea were measured. Pathological changes of pancreas were examined with light microscopy. Body weight, Lee's index, FPG, fasting serum insulin, TG, TC levels and HOMA index in the obese group were higher than those in the control group (P < 0.05), while the level of HDL-C in the obese group was lower than that in the control group (P < 0.05). Pancreatic TG, FFA contents and expression of ADFP in the obese group were significantly higher than those in the control group (P < 0.05), while pancreatic SST level in the obese group was lower than that in the control group (P < 0.05). Obvious pancreatic intra-lobular fatty infiltration was observed in the obese group. After treatment of octreotide, body weight, HOMA index, as well as other plasma parameters as above showed decrease as compared with those in the obese group (P < 0.05). In addition, pancreatic TG, FFA contents and the expression of ADFP in the octreotide treated group were also significantly decreased compared with those in the obese group (P < 0.05), pancreatic SST level was increased in the octreotide treated group than that in the obese group (P < 0.05), and pancreatic intra-lobular fatty infiltration was alleviated. Octreotide might improve pancreatic fatty infiltration, lipid disorder, insulin resistance and alleviate pancreatic injury by down-regulating the expression of ADFP in pancreas, and lowering the levels of plasma glucose and lipid in the high-fat diet induced obesity rats.

Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues.

PubMed

Contreras, G Andres; Strieder-Barboza, Clarissa; de Souza, Jonas; Gandy, Jeff; Mavangira, Vengai; Lock, Adam L; Sordillo, Lorraine M

2017-01-01

The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1) and -10±5 (G2) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L). Concentrations of plasma linoleic and arachidonic acids were increased at PP. In AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2. Concentrations of beta hydroxybutyrate were positively correlated with those of 13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased at PP. These data demonstrate that prepartum adiposity predisposes cows to intense lipolysis post-partum and may exacerbate AT inflammation because of increased production of pro-inflammatory oxylipids including 5- and 15-HETE and 13-HODE. These results support a role for certain linoleic and arachidonic acid-derived oxylipids as positive and negative modulators of AT inflammation during periparturient lipolysis.

Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues

PubMed Central

Strieder-Barboza, Clarissa; de Souza, Jonas; Gandy, Jeff; Mavangira, Vengai; Lock, Adam L.; Sordillo, Lorraine M.

2017-01-01

The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1) and -10±5 (G2) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L). Concentrations of plasma linoleic and arachidonic acids were increased at PP. In AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2. Concentrations of beta hydroxybutyrate were positively correlated with those of 13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased at PP. These data demonstrate that prepartum adiposity predisposes cows to intense lipolysis post-partum and may exacerbate AT inflammation because of increased production of pro-inflammatory oxylipids including 5- and 15-HETE and 13-HODE. These results support a role for certain linoleic and arachidonic acid-derived oxylipids as positive and negative modulators of AT inflammation during periparturient lipolysis. PMID:29206843

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

PubMed

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

PubMed Central

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

Objective It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID:26139105

An Examination of Middle School Agricultural Education and FFA Programs: Survey Results from State FFA Executive Secretaries.

ERIC Educational Resources Information Center

Rossetti, Rosemarie; McCaslin, N. L.

A study collected information from 52 of the 53 state Future Farmers of America (FFA) executive secretaries who were sent questionnaires on middle school student enrollment in agricultural education and membership in the national FFA organization. Results showed that 30 states have agricultural education programs in the middle school level, with a…

β-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3.

PubMed

Won, Yu-Jin; Lu, Van B; Puhl, Henry L; Ikeda, Stephen R

2013-12-04

Free fatty acids receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43), for which the short-chain fatty acids (SCFAs) acetate and propionate are agonist, have emerged as important G-protein-coupled receptors influenced by diet and gut flora composition. A recent study (Kimura et al., 2011) demonstrated functional expression of FFA3 in the rodent sympathetic nervous system (SNS) providing a potential link between nutritional status and autonomic function. However, little is known of the source of endogenous ligands, signaling pathways, or effectors in sympathetic neurons. In this study, we found that FFA3 and FFA2 are unevenly expressed in the rat SNS with higher transcript levels in prevertebral (e.g., celiac-superior mesenteric and major pelvic) versus paravertebral (e.g., superior cervical and stellate) ganglia. FFA3, whether heterologously or natively expressed, coupled via PTX-sensitive G-proteins to produce voltage-dependent inhibition of N-type Ca(2+) channels (Cav2.2) in sympathetic neurons. In addition to acetate and propionate, we show that β-hydroxybutyrate (BHB), a metabolite produced during ketogenic conditions, is also an FFA3 agonist. This contrasts with previous interpretations of BHB as an antagonist at FFA3. Together, these results indicate that endogenous BHB levels, especially when elevated under certain conditions, such as starvation, diabetic ketoacidosis, and ketogenic diets, play a potentially important role in regulating the activity of the SNS through FFA3.

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids.

PubMed

Gallagher, Austin J; Skubel, Rachel A; Pethybridge, Heidi R; Hammerschlag, Neil

2017-01-01

Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species ( n  = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations.

Omega-3 free fatty acids inhibit tamoxifen-induced cell apoptosis.

PubMed

Wu, Shufan; Guo, Yang; Wu, Yikuan; Zhu, Shenglong; He, Zhao; Chen, Yong Q

2015-04-03

Fish oil, which contains omega-3 fatty acids mainly in the form of triglycerides, has benefits for reducing breast cancer risk, similar to tamoxifen action. However, it remains to be elucidated whether the combination of omega-3 free fatty acid (ω-3FFA) with tamoxifen leads to improved treatment in breast cancer. In this study, we observed that ω-3FFA induces MCF-7 cell apoptosis to suppress cell growth. The treatment of breast cancer cells with ω-3FFA attenuated tamoxifen-induced cell apoptosis. ω-3FFA and tamoxifen significantly increased Erk1/2 and Akt phosphorylation levels in a dose and time dependent manner. Compared to ω-3FFA alone, the combination of tamoxifen with ω-3FFA significantly increased Erk1/2 and Akt phosphorylation levels. Because Erk1/2 and Akt activation has been linked to tamoxifen-related anti-estrogen resistance in breast cancer patients, these results indicate that ω-3FFA may interfere with the effects of tamoxifen in the prevention of breast cancer risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

PubMed Central

Hoeks, Joris; van Herpen, Noud A.; Mensink, Marco; Moonen-Kornips, Esther; van Beurden, Denis; Hesselink, Matthijs K.C.; Schrauwen, Patrick

2010-01-01

OBJECTIVE Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS These findings confirm that the insulin-resistant state has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. PMID:20573749

Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.

PubMed

Kliegman, R M

1989-03-01

Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.

Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.

PubMed Central

Boden, G; Chen, X

1995-01-01

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus. PMID:7657800

Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.

PubMed

Boden, G; Chen, X

1995-09-01

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.

Effects of the free fatty acid content in yellow grease on performance, carcass characteristics, and serum lipids in broilers.

PubMed

Wu, H; Gong, L M; Guo, L; Zhang, L Y; Li, J T

2011-09-01

This study was conducted to investigate whether the free fatty acid (FFA) content of yellow grease would influence the performance and carcass characteristics of broiler chicks. A total of 432 one-day-old, male Arbor Acres broilers were randomly allotted to 1 of 4 treatments, with each treatment being applied to 6 pens of 18 chicks. The dietary treatments were based on corn and soybean meal and were supplemented with either soybean oil (2.86% FFA) or yellow grease with a low (2.74%), medium (12.59%), or high (19.05%) FFA content. The fat sources were supplemented at 1.5% of the diet during the starter phase (0 to 21 d) and at 3.0% of the diet during the grower phase (22 to 42 d). From d 0 to 42, the BW gains of chicks fed diets containing soybean oil and yellow grease with 2.74% FFA were similar. As the FFA level in the yellow grease increased, the BW gain of chicks decreased (P < 0.01). The reduction in BW gain appeared to be mediated by a reduction in feed intake. The dressing percentage and the percentage of breast muscle in the carcass were significantly (P < 0.01) lower for broilers fed any yellow grease diet compared with birds fed soybean oil. In contrast, abdominal fat was significantly increased in diets containing yellow grease. These results demonstrate that the performance of birds fed yellow grease with a low content of FFA was essentially equal to that of birds fed soybean oil. However, because yellow grease samples containing FFA levels greater than 2.74% negatively affected bird performance, producers should exercise caution with regard to feeding broilers yellow grease with an elevated FFA content. In 42-d-old broilers, serum total cholesterol and low-density lipoprotein cholesterol levels were elevated in birds fed yellow grease, regardless of the dietary level. In contrast, serum high-density lipoprotein cholesterol and triglyceride levels were unaffected by dietary treatment. Although dietary FFA may influence triglyceride-rich lipoprotein metabolism in broilers, an explanation for the observed effects remains elusive.

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids

PubMed Central

Skubel, Rachel A.; Pethybridge, Heidi R.; Hammerschlag, Neil

2017-01-01

Abstract Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species (n = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations. PMID:28852506

Protective effect of Clerodendron glandulosum extract against experimentally induced metabolic syndrome in rats.

PubMed

Jadeja, Ravirajsinh N; Thounaojam, Menaka C; Ansarullah; Patel, Vaibhav B; Devkar, Ranjitsinh V; Ramachandran, A V

2010-12-01

Metabolic syndrome (MetS) has become one of the major health burdens worldwide. To date, no single pharmacological agent has been developed to correct metabolic abnormalities associated with MetS. Use of indigenous medicinal plants as alternative medicines against MetS could be beneficial due to multiple therapeutic usage, easy availability, and relatively few side effects. To investigate the protective effect of Clerodendron glandulosum Coleb. (Verbenaceae) aqueous leaf extract (CgE) against experimentally induced MetS in rats. Changes in body weight, food and fluid intake, plasma glucose, insulin, fasting insulin resistance index (FIRI), plasma total lipid profile, free fatty acids (FFA), oral glucose tolerance test (OGTT), blood pressure and vascular reactivity have been investigated in various experimental groups. Fructose+CgE groups recorded significant decrement (P <0.05) in plasma glucose, insulin, FIRI, total cholesterol, triglycerides, LDL, VLDL and FFA, whereas plasma HDL level was significantly increased (P <0.05) along with an efficient clearance of glucose during OGTT and lowered area under curve values. FRU+CgE groups also showed significantly decreased (P <0.05) mean arterial blood pressure along with decreased vasoconstriction and increased vasorelaxation in response to administration of various pharmacological agents. These results were comparable with metformin treated rats. C. glandulosum leaf extract ameliorates experimentally induced MetS by improving dyslipidemia and insulin resistance. This study provides the first pharmacological evidence for the protective role of C. glandulosum leaves against experimentally induced MetS. Thus, therapeutic use of C. glandulosum in controlling MetS is indicated.

Systemic Free Fatty Acid Disposal Into Very Low-Density Lipoprotein Triglycerides

PubMed Central

Koutsari, Christina; Mundi, Manpreet S.; Ali, Asem H.; Patterson, Bruce W.; Jensen, Michael D.

2013-01-01

We measured the incorporation of systemic free fatty acids (FFA) into circulating very low-density lipoprotein triglycerides (VLDL-TGs) under postabsorptive, postprandial, and walking conditions in humans. Fifty-five men and 85 premenopausal women with BMI 18–24 (lean) and 27–36 kg/m2 (overweight/obese) received an intravenous bolus injection of [1,1,2,3,3-2H5]glycerol (to measure VLDL-TG kinetics) and either [1-14C]palmitate or [9,10-3H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ∼3× resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates (SRs) were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion, explaining 33–57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG SRs. Regulation of VLDL-TG secretion is complex in that, despite a broad spectrum of physiological FFA concentrations, VLDL-TG SRs did not vary based on different acute substrate availability. PMID:23434937

Defense Priming and Jasmonates: A Role for Free Fatty Acids in Insect Elicitor-Induced Long Distance Signaling

PubMed Central

Li, Ting; Cofer, Tristan; Engelberth, Marie; Engelberth, Jurgen

2016-01-01

Green leaf volatiles (GLV) prime plants against insect herbivore attack resulting in stronger and faster signaling by jasmonic acid (JA). In maize this response is specifically linked to insect elicitor (IE)-induced signaling processes, which cause JA accumulation not only around the damage site, but also in distant tissues, presumably through the activation of electrical signals. Here, we present additional data further characterizing these distal signaling events in maize. Also, we describe how exposure to GLV increases free fatty acid (fFA) levels in maize seedlings, but also in other plants, and how increased fFA levels affect IE-induced JA accumulation. Increased fFA, in particular α-linolenic acid (LnA), caused a significant increase in JA accumulation after IE treatment, while JA induced by mechanical wounding (MW) alone was not affected. We also identified treatments that significantly decreased certain fFA level including simulated wind and rain. In such treated plants, IE-induced JA accumulation was significantly reduced when compared to un-moved control plants, while MW-induced JA accumulation was not significantly affected. Since only IE-induced JA accumulation was altered by changes in the fFA composition, we conclude that changing levels of fFA affect primarily IE-induced signaling processes rather than serving as a substrate for JA. PMID:27135225

Examining Camper Learning Outcomes and Knowledge Retention at Oklahoma FFA Leadership Camp

ERIC Educational Resources Information Center

Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

2014-01-01

The National FFA Organization is committed to providing non-formal learning activities focusing on leadership education. Summer camps are a major component of FFA activities and concentrate on personal growth, leadership development, and recreational activities for youth. This repeated measures study determined the level of cognitive gain and the…

State FFA Officers' Confidence and Trustworthiness of Biotechnology Information Sources

ERIC Educational Resources Information Center

Wingenbach, Gary J.; Rutherford, Tracy A.

2007-01-01

Are state FFA officers' awareness levels of agricultural topics reported in mass media superior to those who do not serve in leadership roles? The purpose of this study was to determine elected state FFA officers' awareness of biotechnology, and their confidence and trust of biotechnology information sources. Descriptive survey methods were used…

Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men

PubMed Central

Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing

2016-01-01

Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Lanzendorf, Susan E; Ratts, Valerie S; Moley, Kelle H

2011-05-01

To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. Prospective cohort study. University in vitro fertilization (IVF) practice. A total of 102 women undergoing IVF. Measurement of FFAs in serum and ovarian follicular fluid. Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Barriers to Participation in the National FFA Organization According to Urban Agriculture Students

ERIC Educational Resources Information Center

Martin, Michael J.; Kitchel, Tracy

2014-01-01

Urban youth engaged in after-school organizations have more positive attributes compared to their unengaged contemporaries. The FFA is one particular intra-curricular organization with after-school components; yet, urban students do not participate in FFA at the same levels as rural students. The purpose of this descriptive study was to explore…

Mechanisms of Insulin Resistance After Insulin-Induced Hypoglycemia in Humans: The Role of Lipolysis

PubMed Central

Lucidi, Paola; Rossetti, Paolo; Porcellati, Francesca; Pampanelli, Simone; Candeloro, Paola; Andreoli, Anna Marinelli; Perriello, Gabriele; Bolli, Geremia B.; Fanelli, Carmine G.

2010-01-01

OBJECTIVE Changes in glucose metabolism occurring during counterregulation are, in part, mediated by increased plasma free fatty acids (FFAs), as a result of hypoglycemia-activated lipolysis. However, it is not known whether FFA plays a role in the development of posthypoglycemic insulin resistance as well. RESEARCH DESIGN AND METHODS We conducted a series of studies in eight healthy volunteers using acipimox, an inhibitor of lipolysis. Insulin action was measured during a 2-h hyperinsulinemic-euglycemic clamp (plasma glucose [PG] 5.1 mmo/l) from 5:00 p.m. to 7:00 p.m. or after a 3-h morning hyperinsulinemic-glucose clamp (from 10 a.m. to 1:00 p.m.), either euglycemic (study 1) or hypoglycemic (PG 3.2 mmol/l, studies 2–4), during which FFA levels were allowed to increase (study 2), were suppressed by acipimox (study 3), or were replaced by infusing lipids (study 4). [6,6-2H2]-Glucose was infused to measure glucose fluxes. RESULTS Plasma adrenaline, norepinephrine, growth hormone, and cortisol levels were unchanged (P > 0.2). Glucose infusion rates (GIRs) during the euglycemic clamp were reduced by morning hypoglycemia in study 2 versus study 1 (16.8 ± 2.3 vs. 34.1 ± 2.2 μmol/kg/min, respectively, P < 0.001). The effect was largely removed by blockade of lipolysis during hypoglycemia in study 3 (28.9 ± 2.6 μmol/kg/min, P > 0.2 vs. study 1) and largely reproduced by replacement of FFA in study 4 (22.3 ± 2.8 μmol/kg/min, P < 0.03 vs. study 1). Compared with study 2, blockade of lipolysis in study 3 decreased endogenous glucose production (2 ± 0.3 vs. 0.85 ± 0.1 μmol/kg/min, P < 0.05) and increased glucose utilization (16.9 ± 1.85 vs. 28.5 ± 2.7 μmol/kg/min, P < 0.05). In study 4, GIR fell by ∼23% (22.3 ± 2.8 μmol/kg/min, vs. study 3, P = 0.058), indicating a role of acipimox per se on insulin action. CONCLUSION Lipolysis induced by hypoglycemia counterregulation largely mediates posthypoglycemic insulin resistance in healthy subjects, with an estimated overall contribution of ∼39%. PMID:20299466

[Change and correlated factors of fasting level of the plasma endotoxin in subjects with different glucose tolerances and body mass indices].

PubMed

Liu, Yun-Hui; Zhao, Tie-Yun; Hou, Li-Qiong

2013-09-01

To investigate the change of the levels of fasting plasma endotoxin (ET) and assess its correlated factors in individuals with different glucose tolerances and body mass indices. The levels of fasting plasma ET were assayed by the endpoint chromogenic limulus amebocyte lysate method in subjects with type 2 diabetes (T2DM), impaired glucose regulation (IGR) and normal glucose tolerance (NGT). The height, body mass, waist, hips, systolic blood pressure and diastolic blood pressure were measured with the conventional methods; body mass index (BMI) and waist hip ratio (WHR) were calculated. All groups were divided into obesity (BMI>or=25 kg/m2) and non-obesity (BMI<25 kg/m2) subgroups. The levels of fasting blood glucose (FBG), 2 hours plasma glucose (2 hPG), fasting insulin (FINS), postprandial insulin (PINS), hemoglobin Alc (HbAlc), blood lipids, free fatty acids (FFA), serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also analyzed, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The relationship of the levels of plasma ET with age, BMI, WHR, blood pressure, FBG, 2 hPG, FINS, PINS, HOMA-IR, HbA1c, blood lipids, FFA, AST and ALT were also analyzed. (1) The levels of plasma ET in T2DM group (n=37) was significantly higher than that in NGT group (n=37) [7. 1 (3. 7-11. 8) EU/mL vs. 4. 5 (2.2-6.3) EU/mL, P<0.05]. The levels of plasma ET in IGR group (n=23) C5.0 (2.4-10.3) EU/mLU was lower than that in T2DM group and higher than NGT group but the differences were not significant (P>0. 05). (2) The levels of plasma ET in the obesity T2DM subgroup was higher than that in the non-obesity T2DM subgroup but the differences were not significant [7. 3 (3. 8-13. 3) EU/mL vs. 7.0 (3. 6-10. 4) EU/mL, P>0. 05]. There was a remarkable difference in the levels of plasma ET between obesity and non-obesity subgroup of IGR (6.8 (2.9-13.2) EU/mL vs. 2.7 (1.6-5. 5) EU/mL, P<0. 05), similarly between obesity and non-obesity subgroup of NGT (6.2 (3. 4-12. 7) EU/mL vs. 2. 8 (1. 8-4. 9) EU/mL, P<0. 05). (3) Multiple linear regression analysis demonstrated that ET wasn' t the important factor influencing FBG and 2 hPG. But BMI and FBG were the important factors influencing ET. 2 hPG and WHR weren't the important factors influencing ET. With the increase in glucose metabolic abnormalities and BMI, the levels of plasma ET are gradually increased. ET isn't the important factor influencing FBG and 2 hPG. BMI and FBG are the important factors in influencing ET.

Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity

PubMed Central

Pereira, Sandra; Yu, Wen Qin; Frigolet, María E; Beaudry, Jacqueline L; Shpilberg, Yaniv; Park, Edward; Dirlea, Cristina; Nyomba, B L Grégoire; Riddell, Michael C; Fantus, I George; Giacca, Adria

2013-01-01

We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase. PMID:23328071

Postprandial Inflammatory Responses and Free Fatty Acids in Plasma of Adults Who Consumed a Moderately High-Fat Breakfast with and without Blueberry Powder in a Randomized Placebo-Controlled Trial.

PubMed

Ono-Moore, Kikumi D; Snodgrass, Ryan G; Huang, Shurong; Singh, Shamsher; Freytag, Tammy L; Burnett, Dustin J; Bonnel, Ellen L; Woodhouse, Leslie R; Zunino, Susan J; Peerson, Janet M; Lee, Joo Young; Rutledge, John C; Hwang, Daniel H

2016-07-01

Saturated fatty acids (FAs) released from triglyceride-rich lipoproteins (TGRLs) activate Toll-like receptor 2 (TLR-2) and induce the expression of proinflammatory cytokines in monocytes. Certain plant polyphenols inhibit TLR-mediated signaling pathways. We determined whether plasma free FAs (FFAs) after a moderately high-fat (MHF, 40% kcal from fat) breakfast modulate the inflammatory status of postprandial blood, and whether blueberry intake suppresses FFA-induced inflammatory responses in healthy humans. Twenty-three volunteers with a mean ± SEM age and body mass index (in kg/m(2)) of 30 ± 3 y and 21.9 ± 0.4, respectively, consumed an MHF breakfast with either a placebo powder or 2 or 4 servings of blueberry powder in a randomized crossover design. The placebo powder was provided on the first test day and the blueberry powder doses were randomized with a 2-wk washout period. Plasma concentrations of lipids, glucose, and cytokines were determined. To determine whether FFAs derived from TGRL stimulate monocyte activation, and whether this is inhibited by blueberry intake, whole blood was treated with lipoprotein lipase (LPL). The median concentrations of FFAs and cytokines [tumor necrosis factor-α, interleukin (IL)-6 and IL-8] in postprandial plasma (3.5 h) decreased compared with fasting plasma regardless of the blueberry intake (P < 0.001 for FFAs and P < 0.05 for cytokines). However, concentrations of FFAs and cytokines including IL-1β increased in LPL-treated whole blood compared with untreated blood samples from participants who consumed the placebo powder. Blueberry intake suppressed IL-1β and IL-6 production in LPL-treated postprandial blood compared with the placebo control when fasting changes were used as a covariate. The plasma FFA concentration may be an important determinant affecting inflammatory cytokine production in blood. Supplementation with blueberry powder did not affect plasma FFA and cytokine concentrations; however, it attenuated the cytokine production induced by ex vivo treatment of whole blood with LPL. This trial was registered at clinicaltrials.gov as NCT01594008. © 2016 American Society for Nutrition.

Aberrant phosphorylation of SMAD4 Thr277-mediated USP9x-SMAD4 interaction by free fatty acids promotes breast cancer metastasis

PubMed Central

Wu, Yong; Yu, Xiaoting; Yi, Xianghua; Wu, Ke; Dwabe, Sami; Atefi, Mohammad; Elshimali, Yahya; Kemp, Kevin T.; Bhat, Kruttika; Haro, Jesse; Sarkissyan, Marianna; Vadgama, Jaydutt V

2017-01-01

Obesity increases the risk of distant metastatic recurrence and reduces breast cancer (BC) survival. However, the mechanisms behind this pathology and identification of relevant therapeutic targets are poorly defined. Plasma free fatty acids (FFA) levels are elevated in obese individuals. Here we report that TGF-β transiently activates ERK and subsequently phosphorylates SMAD4 at Thr277, which facilitates a SMAD4-USP9x interaction, SMAD4 nuclear retention, and stimulates TGF-β /SMAD3-mediated transcription of Twist and Snail. USP9x inhibited the E3 ubiquitin-protein ligase TIF1γ from binding and monoubiquitinating SMAD4, hence maintaining SMAD4 nuclear retention. FFA further facilitated TGF-β-induced ERK activation, SMAD4 phosphorylation and nuclear retention, promoting TGF-β-dependent cancer progression. Inhibition of ERK and USP9x suppressed obesity-induced metastasis. Additionally, clinical data indicated that phospho-ERK and -SMAD4 levels correlate with activated TGF-β signaling and metastasis in overweight/obese patient BC specimens. Altogether, we demonstrate the vital interaction of USP9x and SMAD4 for governing TGF-β signaling and dyslipidemia-induced, aberrant TGF-β activation during BC metastasis. PMID:28115363

Role of calcium and free fatty acids in epinephrine-induced myocardial necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mallov, S.

1983-11-01

A possible mechanism by which large doses of catecholamines produce myocardial necrosis was investigated. Male Sprague-Dawley rats, 275 to 325 g in weight, were injected once, sc, with 3 mg/kg epinephrine (E) or infused iv for 1 hr with E at a rate of 1.2 or 1.7 micrograms/min, and also injected iv with either 45Ca or (3H)palmitic acid (3H-PA) at the same time as or at various periods of time after E administration but exactly 0.5 or 1 hr before death. Controls were injected with saline solution. Heart/plasma ratios of radioactivity (H/P) were determined. The ratios increased in the casemore » of both 45Ca and (3H)PA within 0.5 hr after E, reached peak values after 18 to 24 hr with 45Ca and 3 to 6 hr with (3H)PA, and remained above values for the controls for at least 72 hr with 45Ca and 48 hr with (3H)PA. The rate of 45Ca influx into heart 20 hr after E administration paralleled the severity of the myocardial damage that had been produced. When 45Ca and E were injected simultaneously, H/P increased progressively with time to 30 times control values, indicating the accumulation and retention of Ca in the heart. Under the same conditions, H/P values with (3H)PA also rose but remained constant at a level two to three times that in controls. Total cardiac free fatty acids (FFA) rose slightly and remained constant at the elevated level. It was not possible to distinguish a given point in time at which the increase in either Ca or FFA influx, initially due to the normal pharmacological effect of E, began to occur as a consequence of damage produced by the latter. It is concluded that high concentrations of catecholamines promote the deposition of Ca and FFA in myocardial cells in various forms, and that the deposition of these substances as soaps in the plasma membranes may cause permeability changes that lead to cell injury.« less

Effects of a 3-day fast and of ethanol on splanchnic metabolism of FFA, amino acids, and carbohydrates in healthy young men.

PubMed

Wolfe, B M; Havel, J R; Marliss, E B; Kane, J P; Seymour, J; Ahuja, S P

1976-02-01

Splanchnic metabolism was studied to quantify changes underlying the fatty liver, hyperlipemia, and hypoglycemia produced by ethanol. Four subjects fasted for 15 h were compared with five subjects fasted for 69 h under basal conditions and during continuous intravenous infusion of sufficient ethanol to give a concentration of 3-5 mM in arterial blood plasma. Splanchnic storage of fatty acids was estimated from the difference between uptake of FFA and secretion of derived products. Basal values for splanchnic uptake of FFA were twofold higher after the 69-h fast while splanchnic storage of fatty acids and production of ketone bodies increased threefold. Values for basal secreation into the blood of triglycerides derived from FFA were similar in the two groups. In both nutritional states, the fraction of FFA taken up in the splanchnic region oxidized to ketone bodies and to CO2 fell when ethanol was given because of preferential oxidation of ethanol to acetate, and the fraction esterified rose. However, systemic transport and splanchnic uptake of FFA fell with ethanol in subjects fasted 15 h, so that neither storage of triglycerides in splanchnic tissues nor secretion into the blood increased. In subjects fasted 69 h, ethanol increased transport of FFA and splanchnic storage of fat. In all but one subject it also increased secretion of triglycerides into the blood. The concentration of glucose in blood fell during ethanol infusion in all five subjects undergoing the 69-h fast. Mean splanchnic glucose production was maintained at about one-half of the pre-ethanol value, despite virtual cessation of splanchnic uptake of lactate and of those amino acids that are metabolized via malate. Quantitative estimates of extrasplanchnic metabolism suggest that enhanced formation of alpha-glycerophosphate from glucose, in addition to impaired hepatic gluconeogenesis, may contribute to ethanol-induced hypoglycemia in man.

Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

PubMed

Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

2015-10-01

Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution.

PubMed

Guo, Minshan; Wang, Ke; Qiao, Ning; Fábián, László; Sadiq, Ghazala; Li, Mingzhong

2017-12-04

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), on the dissolution behavior of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analyzed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and nonsink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by predissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility, and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma

PubMed Central

Nath, Aritro; Li, Irene; Roberts, Lewis R.; Chan, Christina

2015-01-01

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide, and the factors influencing HCC progression are poorly understood. Here we reveal that HCC progression via induction of epithelial-mesenchymal transition (EMT) is closely associated with the expression of CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although obesity is manifested as elevated FFA levels, the degree of EMT was not associated with the body mass index of the patients, highlighting the specific roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated these effects. Furthermore, the Wnt and TGF-β signaling pathways were activated upon FFA treatment, potentially acting as upstream activators of the EMT program. These results provide the first direct evidence associating CD36 and elevated FFAs with HCC progression. PMID:26424075

Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.

PubMed

Nath, Aritro; Li, Irene; Roberts, Lewis R; Chan, Christina

2015-10-01

Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide, and the factors influencing HCC progression are poorly understood. Here we reveal that HCC progression via induction of epithelial-mesenchymal transition (EMT) is closely associated with the expression of CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although obesity is manifested as elevated FFA levels, the degree of EMT was not associated with the body mass index of the patients, highlighting the specific roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated these effects. Furthermore, the Wnt and TGF-β signaling pathways were activated upon FFA treatment, potentially acting as upstream activators of the EMT program. These results provide the first direct evidence associating CD36 and elevated FFAs with HCC progression.

Improving metabolic stability with deuterium: The discovery of GPU-028, a potent free fatty acid receptor 4 agonists.

PubMed

Li, Zheng; Xu, Xue; Li, Gang; Fu, Xiaoting; Liu, Yanzhi; Feng, Yufeng; Wang, Mingyan; Ouyang, Yunting; Han, Jing

2017-12-15

The free fatty acid receptor 4 (FFA4) has emerged as a promising anti-diabetic target due to its function in improvement of insulin secretion and insulin resistance. The FFA4 agonist TUG-891 revealed great potential as a widely used pharmacological tool, but it has been suffered from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify metabolically stable analog without influence on physiological mechanism of TUG-891, we tried to incorporate deuterium at the α-position of phenylpropionic acid to afford compound 4 (GPU-028). As expected, GPU-028 revealed a longer half-life (T 1/2  = 1.66 h), lower clearance (CL = 0.97 L/h/kg) and higher maximum plasma concentration (C max  = 2035.23 μg/L), resulting in a 4-fold higher exposure than TUG-891. Although GPU-028 exhibited a similar agonistic activity in comparison to TUG-891, the hypoglycemic effect of GPU-028 was better than that of TUG-891 after treatment over four weeks in diet-induced obese mice. These positive results indicated that GPU-028 might be a better pharmacological tool than TUG-891 to explore physiological function of FFA4, especially on the in vivo study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

NASA Technical Reports Server (NTRS)

Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

1976-01-01

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid.

PubMed

Heo, Wan; Kim, Jun Ho; Pan, Jeong Hoon; Kim, Young Jun

2016-02-17

In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA.

In silico screening for candidate chassis strains of free fatty acid-producing cyanobacteria.

PubMed

Motwalli, Olaa; Essack, Magbubah; Jankovic, Boris R; Ji, Boyang; Liu, Xinyao; Ansari, Hifzur Rahman; Hoehndorf, Robert; Gao, Xin; Arold, Stefan T; Mineta, Katsuhiko; Archer, John A C; Gojobori, Takashi; Mijakovic, Ivan; Bajic, Vladimir B

2017-01-05

Finding a source from which high-energy-density biofuels can be derived at an industrial scale has become an urgent challenge for renewable energy production. Some microorganisms can produce free fatty acids (FFA) as precursors towards such high-energy-density biofuels. In particular, photosynthetic cyanobacteria are capable of directly converting carbon dioxide into FFA. However, current engineered strains need several rounds of engineering to reach the level of production of FFA to be commercially viable; thus new chassis strains that require less engineering are needed. Although more than 120 cyanobacterial genomes are sequenced, the natural potential of these strains for FFA production and excretion has not been systematically estimated. Here we present the FFA SC (FFASC), an in silico screening method that evaluates the potential for FFA production and excretion of cyanobacterial strains based on their proteomes. A literature search allowed for the compilation of 64 proteins, most of which influence FFA production and a few of which affect FFA excretion. The proteins are classified into 49 orthologous groups (OGs) that helped create rules used in the scoring/ranking of algorithms developed to estimate the potential for FFA production and excretion of an organism. Among 125 cyanobacterial strains, FFASC identified 20 candidate chassis strains that rank in their FFA producing and excreting potential above the specifically engineered reference strain, Synechococcus sp. PCC 7002. We further show that the top ranked cyanobacterial strains are unicellular and primarily include Prochlorococcus (order Prochlorales) and marine Synechococcus (order Chroococcales) that cluster phylogenetically. Moreover, two principal categories of enzymes were shown to influence FFA production the most: those ensuring precursor availability for the biosynthesis of lipids, and those involved in handling the oxidative stress associated to FFA synthesis. To our knowledge FFASC is the first in silico method to screen cyanobacteria proteomes for their potential to produce and excrete FFA, as well as the first attempt to parameterize the criteria derived from genetic characteristics that are favorable/non-favorable for this purpose. Thus, FFASC helps focus experimental evaluation only on the most promising cyanobacteria.

Decreased expression of adipose CD36 and FATP1 are associated with increased plasma nonesterified fatty acids during prolonged fasting in northern elephant seal pups (Mirounga angustirostris)

USDA-ARS?s Scientific Manuscript database

The northern elephant seal undergoes a 2-3 month post-weaning fast during which it depends primarily on the oxidation of fatty acids to meet its energetic demands. The concentration of plasma free fatty acids (FFA) increases and is associated with the development of insulin resistance in late-fasted...

Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism.

PubMed

Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

2014-03-21

We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of n-3 fatty acids on free tryptophan and exercise fatigue.

PubMed

Huffman, Derek M; Altena, Thomas S; Mawhinney, Thomas P; Thomas, Tom R

2004-08-01

Free tryptophan (Trp), which is augmented by liberated free fatty acids (FFA) from adipose tissue, can induce mental fatigue via serotonin during exercise. Since an attenuation in FFA has been observed with omega-3 fatty acid (n-3fa) use, our purpose was to examine the effect of n-3fa supplementation on free Trp availability and exercise fatigue. Ten recreationally trained men ( n=5) and women ( n=5), with maximal oxygen consumption (VO(2max))of 51.6 (3.0) and 44.3 (1.4) ml kg(-1) min(-1), respectively, were studied on two occasions following an overnight fast, before and after n-3fa supplementation (4 g day(-1) for 4 weeks). The exercise trials consisted of a 75-min treadmill run at 60% VO(2max) followed immediately by a high-intensity incremental bout to fatigue. Measurements included exercise monitors, plasma volume (PV), triglycerides (TG), FFA, glycerol, lactate, and glucose. Free Trp and branched-chain amino acids (BCAA) were measured and correlated with time to fatigue; all blood variables were corrected for PV. Free Trp, lactate, glucose, FFA, and glycerol were not significantly different between trials, but TG ( P<0.001) and the free Trp/BCAA ratio were significantly lower after n-3fa use [1.76 (0.18)x10(-2) microg ml(-1)] versus before supplementation [2.17 (0.22), P=0.033]. There was a non-significant increase in time to fatigue after supplementation [10.2 (0.3) min] versus before n-3fa use [9.7 (0.2), P=0.068], and a tendency for higher BCAA levels after supplementation, P=0.068. However, neither free Trp nor the free Trp/BCAA ratio significantly predicted time to fatigue. In conclusion, n-3fa supplementation did not diminish free Trp concentrations or significantly improve endurance performance during a maximal bout of exercise.

Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

PubMed

Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

2010-08-01

The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

Aberrant Phosphorylation of SMAD4 Thr277-Mediated USP9x-SMAD4 Interaction by Free Fatty Acids Promotes Breast Cancer Metastasis.

PubMed

Wu, Yong; Yu, Xiaoting; Yi, Xianghua; Wu, Ke; Dwabe, Sami; Atefi, Mohammad; Elshimali, Yahya; Kemp, Kevin T; Bhat, Kruttika; Haro, Jesse; Sarkissyan, Marianna; Vadgama, Jaydutt V

2017-03-15

Obesity increases the risk of distant metastatic recurrence and reduces breast cancer survival. However, the mechanisms behind this pathology and identification of relevant therapeutic targets are poorly defined. Plasma free fatty acids (FFA) levels are elevated in obese individuals. Here we report that TGFβ transiently activates ERK and subsequently phosphorylates SMAD4 at Thr277, which facilitates a SMAD4-USP9x interaction, SMAD4 nuclear retention, and stimulates TGFβ/SMAD3-mediated transcription of Twist and Snail. USP9x inhibited the E3 ubiquitin-protein ligase TIF1γ from binding and monoubiquitinating SMAD4, hence maintaining the SMAD4 nuclear retention. FFA further facilitated TGFβ-induced ERK activation, SMAD4 phosphorylation, and nuclear retention, promoting TGFβ-dependent cancer progression. Inhibition of ERK and USP9x suppressed obesity-induced metastasis. In addition, clinical data indicated that phospho-ERK and -SMAD4 levels correlate with activated TGFβ signaling and metastasis in overweight/obese patient breast cancer specimens. Altogether, we demonstrate the vital interaction of USP9x and SMAD4 for governing TGFβ signaling and dyslipidemia-induced aberrant TGFβ activation during breast cancer metastasis. Cancer Res; 77(6); 1383-94. ©2017 AACR . ©2017 American Association for Cancer Research.

Does 8 weeks of strenuous bicycle exercise improve diabetes-related inflammatory cytokines and free fatty acids in type 2 diabetes patients and individuals at high-risk of metabolic syndrome?

PubMed

Madsen, Søren Møller; Thorup, Anne Cathrine; Bjerre, Mette; Jeppesen, Per Bendix

2015-01-01

In the present study, the effects of 8 weeks of low volume high intensity interval training (HIIT) was investigated on circulating diabetes-related cytokines and free fatty acids (FFA) in adults with type 2 diabetes (T2D) and matched controls (CON). Participants exercised for 8 weeks (3 weekly sessions: 10 × 60 sec HIIT) on a cycle ergometer supervised by medical staff. Prior to the intervention and after the last HIIT session, venous blood samples were collected. Circulating omentin-1 concentrations increased significantly in both the CON-group (p = 0.003) and in the T2D-group (p = 0.002). Pentraxin-3 (p = 0.010) and IL-1ra (p = 0.031) levels increased significantly in the CON-group. Plasma FFA in the T2D-group was significantly reduced after 60 min (p = 0.011). Post HIIT area under curve of circulating FFAs was reduced by -17.73 ± 6.99% (p = 0.041) in the T2D-group. We observed only modest exercise-induced improvements of multiple diabetes-related cytokines. Circulating levels of FFAs were significantly lowered in the T2D-group.

A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study.

PubMed

Davidson, Michael H; Johnson, Judith; Rooney, Michael W; Kyle, Michael L; Kling, Douglas F

2012-01-01

Omega-3 (OM-3) fatty acid products are indicated for the treatment of severe hypertriglyceridemia; however, the omega-3-acid ethyl ester (OM-3 EE) formulations require significant pancreatic lipase stimulation with high-fat meals for adequate intestinal absorption of the metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A novel omega-3 free fatty acid (OM-3 FFA) formulation (Epanova(®), Omthera Pharmaceuticals Inc., Princeton, NJ) was developed to maximize EPA and DHA bioavailability during a low-fat diet. To compare the relative bioavailability of EPA and DHA from single 4-gram doses of OM-3 FFA and a prescription OM-3 EE (Lovaza(®), GlaxoSmithKline, Research Triangle Park, NC). This was a randomized, open-label, single dose, 4-way crossover, bioavailability study of OM-3 FFA and OM-3 EE administered during periods of low-fat and high-fat consumption to 54 overweight adults. Bioavailability was determined by the ln-transformed area under the plasma concentration versus time curve (AUC(0-t)) during a 24-hour interval for EPA and DHA (baseline-adjusted). The baseline-adjusted AUC(0-t) for total EPA + DHA during the low-fat period was 4.0-fold greater with OM-3 FFA compared with OM-3 EE (2650.2 vs 662.0 nmol·h/mL, respectively; P < .0001). During the high-fat period, AUC(0-t) for OM-3 FFA was approximately 1.3-fold greater than OM-3 EE (P < .0001). During the low-fat period, 30 of 51 (58.8%) subjects dosed with OM-3 FFA maintained an AUC(0-t) that was ≥50% of the respective high-fat AUC(0-t) in contrast to only 3 of 50 (6.0%) subjects dosed with OM-3 EE. During a low-fat consumption period, the OM-3 FFA formulation provided dramatically improved bioavailability over the OM-3 EE formulation in overweight subjects. These findings offer a potential therapeutic advantage of the OM-3 FFA formulation for the treatment of severe hypertriglyceridemia as these patients are expected to adhere to a low-fat diet. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Influence of liver cancer on lipid and lipoprotein metabolism

PubMed Central

Jiang, Jingting; Nilsson-Ehle, Peter; Xu, Ning

2006-01-01

Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx) that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL). Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG), cholesterol, free fatty acids (FFA), HDL, low-density lipoproteins (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (apoAI) and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a) might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents. PMID:16515689

Changes in metabolite, energy metabolism related enzyme activities and peripheral blood mononuclear cell (PBMC) populations in beef heifers with two differing liveweight change profiles in New Zealand.

PubMed

Mori, A; Kenyon, P R; Mori, N; Yamamoto, I; Tanaka, Y; Suzuki, N; Tazaki, H; Ozawa, T; Hayashi, T; Hickson, R E; Morris, S T; Blair, H; Arai, T

2008-02-01

Metabolite and immunoreactive insulin (IRI) concentrations, energy metabolism related enzymes activities and peripheral blood mononuclear cell (PBMC) populations were measured in blood of pregnant Angus heifers with differing liveweight change profiles (gaining or losing), in New Zealand to investigate the meanings of those parameters in the restricted feeding beef heifers. Beef heifers losing liveweight (-412 g/day) showed significantly lower concentrations of plasma IRI, and higher concentrations of plasma free fatty acid (FFA) than heifers gaining liveweight (483 g/day). The cytosolic and mitochondrial malate dehydrogenase (MDH) activities and MDH/lactate dehydrogenase (M/L) ratio in leukocytes of the liveweight losing heifers were significantly higher than those the liveweight gaining heifers. Percentages of cluster of differentiation (CD) 3 positive cells and natural killer (NK) cells in PBMC decreased significantly in the liveweight losing heifers compared to those in the liveweight gaining heifers. Plasma IRI and FFA concentrations, leukocyte cytosolic and mitochondrial MDH activities and CD3 positive and NK cell populations may be useful markers to evaluate metabolic conditions and immunity in the restricted feeding beef heifers.

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

PubMed Central

Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

2015-01-01

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

Comparison of digital color fundus imaging and fluorescein angiographic findings for the early detection of diabetic retinopathy in young type 1 diabetic patients.

PubMed

Kapsala, Z; Anastasakis, A; Mamoulakis, D; Maniadaki, I; Tsilimbaris, M

2018-01-01

To compare the findings from digital 7-field color fundus (CF) photography and fundus fluorescein angiography (FFA) in young patients with diabetes mellitus (DM) type 1 without known diabetic retinopathy. In this prospective, observational cohort study, 54 type 1 diabetic patients were recruited. Participants had been diagnosed with diabetes mellitus (DM) for at least 6 years, had Best Corrected Visual Acuity of 20/25 or better and did not have any known retinal pathology. One hundred and seven eyes were analyzed. All patients underwent a complete ophthalmic examination in the Retina Service of a University Eye Clinic including digital CF imaging and FFA. The mean age of the patients was 18.6 years. Mean duration of DM was 11.3 years, and mean haemoglobin A1c (HbA1c) level was 8.6%. Of the 107 eyes, 8 eyes (7.5%) showed microvascular abnormalities on CF images, while FFA images revealed changes in 26 eyes (24.3%). Hence, 18 of the 26 eyes showing abnormalities on FFA did not show any abnormalities on CF images. Mean DM duration in the patient group with detectable microvascular changes was found to be significantly higher compared to patients without changes, while no difference in HbA1c levels, serum lipid levels or blood pressure was observed. Comparison of digital CF and FFA findings for the detection of diabetic microvascular changes in type 1 diabetic patients showed that FFA reveals more information about retinal vascular pathology for early detection of diabetic retinopathy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease.

PubMed

Softic, Samir; Cohen, David E; Kahn, C Ronald

2016-05-01

Nonalcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome. Overconsumption of high-fat diet (HFD) and increased intake of sugar-sweetened beverages are major risk factors for development of NAFLD. Today the most commonly consumed sugar is high fructose corn syrup. Hepatic lipids may be derived from dietary intake, esterification of plasma free fatty acids (FFA) or hepatic de novo lipogenesis (DNL). A central abnormality in NAFLD is enhanced DNL. Hepatic DNL is increased in individuals with NAFLD, while the contribution of dietary fat and plasma FFA to hepatic lipids is not significantly altered. The importance of DNL in NAFLD is further established in mouse studies with knockout of genes involved in this process. Dietary fructose increases levels of enzymes involved in DNL even more strongly than HFD. Several properties of fructose metabolism make it particularly lipogenic. Fructose is absorbed via portal vein and delivered to the liver in much higher concentrations as compared to other tissues. Fructose increases protein levels of all DNL enzymes during its conversion into triglycerides. Additionally, fructose supports lipogenesis in the setting of insulin resistance as fructose does not require insulin for its metabolism, and it directly stimulates SREBP1c, a major transcriptional regulator of DNL. Fructose also leads to ATP depletion and suppression of mitochondrial fatty acid oxidation, resulting in increased production of reactive oxygen species. Furthermore, fructose promotes ER stress and uric acid formation, additional insulin independent pathways leading to DNL. In summary, fructose metabolism supports DNL more strongly than HFD and hepatic DNL is a central abnormality in NAFLD. Disrupting fructose metabolism in the liver may provide a new therapeutic option for the treatment of NAFLD.

Role of Dietary Fructose and Hepatic de novo Lipogenesis in Fatty Liver Disease

PubMed Central

Softic, Samir; Cohen, David E.; Kahn, C. Ronald

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome. Overconsumption of high-fat diet (HFD) and increased intake of sugar sweetened beverages are major risk-factors for development of NAFLD. Today the most commonly consumed sugar is high fructose corn syrup. Hepatic lipids may be derived from dietary intake, esterification of plasma free fatty acids (FFA) or hepatic de novo lipogenesis (DNL). A central abnormality in NAFLD is enhanced de novo lipogenesis. Hepatic de novo lipogenesis is increased in individuals with NAFLD, while the contribution of dietary fat and plasma FFA to hepatic lipids is not significantly altered. The importance of DNL in NAFLD is further established in mouse studies with knockout of genes involved in this process. Dietary fructose increases levels of enzymes involved in DNL even more strongly than HFD. Several properties of fructose metabolism make it particularly lipogenic. Fructose is absorbed via portal vein and delivered to the liver in much higher concentrations as compared to other tissues. Fructose increases protein levels of all DNL enzymes during its conversion into triglycerides. Additionally, fructose supports lipogenesis in the setting of insulin resistance as fructose does not require insulin for its metabolism and it directly stimulates SREBP1c, a major transcriptional regulator of DNL. Fructose also leads to ATP depletion and suppression of mitochondrial fatty acid oxidation resulting in increased production of reactive oxygen species. Furthermore fructose promotes ER stress and uric acid formation, additional insulin independent pathways leading to DNL. In summary, fructose metabolism supports DNL more strongly than HFD and hepatic DNL is a central abnormality in NAFLD. Disrupting fructose metabolism in the liver may provide a new therapeutic option for the treatment of NAFLD. PMID:26856717

MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR).

PubMed

An, Xianchao; Yang, Zonglin; An, Zhengzhuang

2017-05-16

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The objective of our study was to explore the effect of polymorphism in miR-149 on the pathogenesis of NAFLD. MATERIAL AND METHODS Real-time PCR was performed to explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and luciferase assay were investigated to verify MTHFR was the target gene of miR-149. Finally, Western-blot analysis and real-time PCR were performed to confirm the control of MTHFR by miR-149. RESULTS In this study, we found that miR-149 was apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR in hepatocytes genotyped as TT treated with FFA was evidently downregulated compared to control. Whereas, FFA had no obvious effect on MTHFR level in hepatocytes genotyped as CC. We searched an online miRNA database and found that miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149 mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose-dependently increased the level of MTHFR. And in hepatocytes genotyped as CC treated with or without FFA exhibited a similar inhibition effect of miR-149 on expression of MTHFR. CONCLUSIONS The data suggested that the polymorphism in miR-149 played an important role in the development of NAFLD via altering the expression of miR-149 as well as its target, MTHFR.

MiR-149 Compromises the Reactions of Liver Cells to Fatty Acid via its Polymorphism and Increases Non-Alcoholic Fatty Liver Disease (NAFLD) Risk by Targeting Methylene Tetrahydrofolate Reductase (MTHFR)

PubMed Central

An, Xianchao; Yang, Zonglin; An, Zhengzhuang

2017-01-01

Background Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem, and microRNA (miRNA) has been reported to be involved in NAFLD. The objective of our study was to explore the effect of polymorphism in miR-149 on the pathogenesis of NAFLD. Material/Methods Real-time PCR was performed to explore the effect of long-chain fatty acid (FFA) on the level of miR-149 and methylene tetrahydrofolate reductase (MTHFR). Then in-silicon analysis and luciferase assay were investigated to verify MTHFR was the target gene of miR-149. Finally, Western-blot analysis and real-time PCR were performed to confirm the control of MTHFR by miR-149. Results In this study, we found that miR-149 was apparently upregulated in hepatocytes genotyped as TT treated with FFA; and MTHFR in hepatocytes genotyped as TT treated with FFA was evidently downregulated compared to control. Whereas, FFA had no obvious effect on MTHFR level in hepatocytes genotyped as CC. We searched an online miRNA database and found that miR-149 was a regulator of MTHFR expression, which was confirmed by luciferase assay. In hepatocytes genotyped as TT and treated with or without FFA, miR-149 mimic dose-dependently decreased the level of MTHFR, and miR-149 inhibitor dose-dependently increased the level of MTHFR. And in hepatocytes genotyped as CC treated with or without FFA exhibited a similar inhibition effect of miR-149 on expression of MTHFR. Conclusions The data suggested that the polymorphism in miR-149 played an important role in the development of NAFLD via altering the expression of miR-149 as well as its target, MTHFR. PMID:28507283

Metabolic syndrome, hyperinsulinemia, and cancer.

PubMed

Hsu, Isabel R; Kim, Stella P; Kabir, Morvarid; Bergman, Richard N

2007-09-01

The term metabolic syndrome describes the association between obesity, insulin resistance, and the risk of several prominent chronic diseases, including cancer. The causal link between many of these components remains unexplained, however. What is clear are the events that precede the development of the syndrome itself. In animal models, a fat-supplemented diet causes 1) lipid deposition in adipose depots, 2) insulin resistance of liver and skeletal muscle, and 3) hyperinsulinemia. One hypothesis relating fat deposition and insulin resistance involves enhanced lipolysis in the visceral depot, which leads to an increase in free fatty acid (FFA) flux. Increased mass of stored lipid and insulin resistance of visceral adipocytes favors lipolysis. Additionally, hypersensitivity of visceral adipose cells to sympathetic nervous system stimulation leads to increased lipolysis in the obese state. However, little evidence is available for enhanced plasma FFA concentrations in the fasting state. We measured FFA concentrations over a 24-h day in obese animals and found that plasma FFAs are elevated in the middle of the night, peaking at 0300. Therefore, it is possible that nocturnal lipolysis increases exposure of liver and muscle to FFAs at night, thus causing insulin resistance, which may play a role in hyperinsulinemic compensation to insulin resistance. Nocturnal lipolysis secondary to sympathetic stimulation may not only cause insulin resistance but also be responsible for hyperinsulinemia by stimulating secretion and reducing clearance of insulin by the liver. The resulting syndrome-elevated nocturnal FFAs and elevated insulin-may synergize and increase the risk of some cancers. This possible scenario needs further study.

High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

PubMed

Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

Interrelations in the Oxidative Metabolism of Free Fatty Acids, Glucose, and Glycerol in Normal and Hyperlipemic Patients A COMPARTMENTAL MODEL

PubMed Central

Malmendier, C. L.; Delcroix, C.; Berman, M.

1974-01-01

Palmitate, glucose, and glycerol oxidation to CO2 have been investigated in the fasted state in ten normal subjects and nine patients (six hyperlipoproteinemias, one xanthomatosis, and two glycogenosis) after intravenous injection of [1-14C]palmitate, [1-14C]glucose, or [1-14C]glycerol in tracer amounts. The specific activities and concentrations of plasma palmitate, glycerol, or glucose and expired CO2 were measured at various intervals after the injection for a period of 24 h. All the studies were analyzed in terms of a multicompartment model describing the structure for each of the subsystems, the transfer of carbon label between subsystems, and the oxidation to CO2. A bicarbonate subsystem was also included in the model to account for its role in shaping the CO2 curves. All the CO2 activity following a palmitate injection could be accounted for by a direct oxidative pathway from plasm FFA with the addition of a 20-min delay compartment. The same also applied to glucose, except that the delay compartment had a mean time of about 150 min. Only about a third of the injected glycerol was directly oxidized to CO2 from plasma; the delay time was about 4 min. Most of the remainder was converted to glucose. In normals about 45% of the FFA is oxidized to CO2 directly. This constitutes about 30% of the total CO2 output. In hyperlipemia the CO2 output is nearly unchanged and the contribution from FFA is nearly the same. There is a considerable increase (factor of 2), however, in FFA mobilization, most of which is probably diverted to triglyceride synthesis. The glucose and glycerol subsystems are roughly the same in normals and hyperlipemics. About 50% of glucose is oxidized by the direct pathways which accounts for about 35% of the CO2 output. Glycerol accounts for only 1.5% of the CO2 produced. Major changes occurred in the glycerol and glucose subsystems in glycogenosis. The changes are consistent with the known deficiency in glucose-6-phosphatase in this disorder. There is a considerable reduction (factor of 2 or more) in the release of glucose to plasma (gluconeogenesis) and in the conversion of glycerol to glucose. Despite the integration of the kinetics of the glucose, glycerol, and FFA subsystems over a 24-h period, 36% of the CO2 production was still unaccounted for in normals and 50% in hyperlipemics. Thus, some of the carbon must wind up in very slowly turning-over pools which supply CO2 through subsystems not covered in these studies (triglycerides, glycogen, amino acids, etc.). All the modeling was carried out with the aid of the SAAM25 computer program. PMID:4527190

What's behind a face: person context coding in fusiform face area as revealed by multivoxel pattern analysis.

PubMed

van den Hurk, J; Gentile, F; Jansma, B M

2011-12-01

The identification of a face comprises processing of both visual features and conceptual knowledge. Studies showing that the fusiform face area (FFA) is sensitive to face identity generally neglect this dissociation. The present study is the first that isolates conceptual face processing by using words presented in a person context instead of faces. The design consisted of 2 different conditions. In one condition, participants were presented with blocks of words related to each other at the categorical level (e.g., brands of cars, European cities). The second condition consisted of blocks of words linked to the personality features of a specific face. Both conditions were created from the same 8 × 8 word matrix, thereby controlling for visual input across conditions. Univariate statistical contrasts did not yield any significant differences between the 2 conditions in FFA. However, a machine learning classification algorithm was able to successfully learn the functional relationship between the 2 contexts and their underlying response patterns in FFA, suggesting that these activation patterns can code for different semantic contexts. These results suggest that the level of processing in FFA goes beyond facial features. This has strong implications for the debate about the role of FFA in face identification.

A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism☆

PubMed Central

Jiang, Xiong; Bollich, Angela; Cox, Patrick; Hyder, Eric; James, Joette; Gowani, Saqib Ali; Hadjikhani, Nouchine; Blanz, Volker; Manoach, Dara S.; Barton, Jason J.S.; Gaillard, William D.; Riesenhuber, Maximilian

2013-01-01

Individuals with Autism Spectrum Disorder (ASD) appear to show a general face discrimination deficit across a range of tasks including social–emotional judgments as well as identification and discrimination. However, functional magnetic resonance imaging (fMRI) studies probing the neural bases of these behavioral differences have produced conflicting results: while some studies have reported reduced or no activity to faces in ASD in the Fusiform Face Area (FFA), a key region in human face processing, others have suggested more typical activation levels, possibly reflecting limitations of conventional fMRI techniques to characterize neuron-level processing. Here, we test the hypotheses that face discrimination abilities are highly heterogeneous in ASD and are mediated by FFA neurons, with differences in face discrimination abilities being quantitatively linked to variations in the estimated selectivity of face neurons in the FFA. Behavioral results revealed a wide distribution of face discrimination performance in ASD, ranging from typical performance to chance level performance. Despite this heterogeneity in perceptual abilities, individual face discrimination performance was well predicted by neural selectivity to faces in the FFA, estimated via both a novel analysis of local voxel-wise correlations, and the more commonly used fMRI rapid adaptation technique. Thus, face processing in ASD appears to rely on the FFA as in typical individuals, differing quantitatively but not qualitatively. These results for the first time mechanistically link variations in the ASD phenotype to specific differences in the typical face processing circuit, identifying promising targets for interventions. PMID:24179786

Texas FFA Officer Perceptions of Good Followership

ERIC Educational Resources Information Center

Ferrell, Susan Kate; Boyd, Barry L.; Rayfield, John

2013-01-01

This study examines Texas FFA officers' perceptions regarding the traits and characteristics that good followers possess. A content analysis of officer responses to an open-ended question found that these young leaders have a limited level of understanding of what constitutes a good follower. Furthermore, female respondents placed a greater…

Occupational Aspirations of State FFA Contest and Award Winners.

ERIC Educational Resources Information Center

Bowen, Blannie E.; Doerfert, David L.

1989-01-01

A study explored the occupational aspirations of 300 (of 503) students with high levels of participation in Future Farmers of America's (FFA) Computers in Agriculture (CIA), Proficiency Award (PA), and Prepared and Extemporaneous Speaking (PES) contests. CIA and PES winners aspired to professional occupations more than PA winners. PES winners…

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.

PubMed Central

Tisdale, M. J.; Brennan, R. A.

1988-01-01

A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size. PMID:3219268

Non-alcoholic steatohepatitis: review of a growing medical problem.

PubMed

Te Sligte, K.; Bourass, I.; Sels, J.P.; Driessen, A.; Stockbrugger, R.W.; Koek, G.H.

2004-02-01

Non-alcoholic steatohepatitis (NASH) is a metabolic liver disorder that is seen in 2-6% of the general population. It manifests itself by elevated liver enzymes, frequently without symptoms. The histological findings include steatosis, inflammation, fibrosis, and cirrhosis. Three case reports are presented to illustrate features of NASH. A two-hit model has been proposed in the pathogenesis of NASH. The first hit is hepatic steatosis. A hypercaloric diet with high levels of carbohydrates and saturated fatty acids results in elevated plasma free fatty acids (FFA) and expands the adipose tissue. Insulin resistance develops and augments steatosis. Oxidation of FFA yields toxic free radicals, resulting in lipid peroxidation. They cause the second hits: increased oxidative stress on hepatocytes and induction of pro-inflammatory cytokines. When the antioxidant capacities of the liver are insufficient, mitochondrial dysfunction and tumor necrosis factor alpha (TNF-alpha) cause inflammation and fibrosis. Treatment consists of life style modifications, particularly weight loss and exercise. Many drugs have been tried in the treatment of NASH. The insulin-sensitizing drugs metformin, rosiglitazone, and pioglitazone, and the antioxidant vitamin E show promising results. Further investigation of therapeutic options is needed to direct the choice of therapy in the future.

Physiological response of Zebu and taurine oxen to draught work.

PubMed

Zanzinger, J; Becker, K; Rometsch, M

1993-07-15

Four Zebu and four Simmental oxen were submitted to continuous and to graded draught work. Venous blood samples were taken before, during, and after exercise at intervals of 2-5 min. Anaerobic threshold was reached at a draught power of 1.6 +/- 0.06 kW for Zebu and 0.7 +/- 0.07 kW for Simmental. Corresponding plasma lactate concentrations were 1.7 +/- 0.2 mmol/liter and 1.6 +/- 0.3 mmol/liter, respectively. Partial pressure of oxygen (pvO2), carbon dioxide (pvCO2), and plasma free fatty acids (FFA) during and after work differed between breeds (P approximately .001) and individuals (P approximately .05). After work, an up to 8-fold increase in FFA was found. Highest plasma lactate concentrations during continuous maximal draught were 3.75 +/- 1.76 (Zebu) and 6.01 +/- 0.88 mmol/liter (Simmental). Acid-base-state during and after exhaustive work remained stable. Heart rate in both breeds did not exceed 190 min-1. It is concluded that 1) even during heavy draught work, anaerobic energy formation plays a minor role for cattle, 2) fatigue in working oxen may be related to cardiovascular limitations, and 3) the physical fitness of European beef-breed oxen is lower compared to multipurpose African Zebu oxen.

Lack of Day/Night variation in fibroblast growth factor 21 levels in young healthy men.

PubMed

Foo, J-P; Aronis, K N; Chamberland, J P; Mantzoros, C S

2015-06-01

Fibroblast growth factor (FGF) 21 is an endocrine factor with an emerging role as a metabolic regulator. We previously reported the presence of a significant day/night variation of FGF-21 in energy-replete, healthy female subjects. However the day/night patterns of secretion in male subjects remain to be fully elucidated. To elucidate day/night pattern of FGF-21 levels in male subjects in the energy-replete state, its relationship to FFA and to investigate whether a sexual dimorphism exists in FGF-21 physiology. Eight healthy lean male subjects were studied for up to 5 days while on an isocaloric diet. Blood samples were obtained for measurement of FGF-21 and free fatty acids (FFA) hourly from 0800 AM on day 4 till 0800AM on day 5. FGF-21 did not exhibit any statistically significant day/night variation pattern of circulating FGF-21 levels during the isocaloric fed state in male subjects. FGF-21 levels in male subjects are closely cross-correlated with FFA levels, similar to female subjects. A sexual dimorphism exists in FGF-21 physiology; that as opposed to female subjects, no significant day/night variation exists in FGF-21 rhythm in male subjects in the energy-replete state. Circulating pattern of FGF-21, similar to the female subjects, was highly cross-correlated to the FFA levels in the male subjects, signifying that the sexual dimorphism in FGF-21 physiology may be related to the differing lipid metabolism in both the genders.

Greater sensitivity of the cortical face processing system to perceptually-equated face detection

PubMed Central

Maher, S.; Ekstrom, T.; Tong, Y.; Nickerson, L.D.; Frederick, B.; Chen, Y.

2015-01-01

Face detection, the perceptual capacity to identify a visual stimulus as a face before probing deeper into specific attributes (such as its identity or emotion), is essential for social functioning. Despite the importance of this functional capacity, face detection and its underlying brain mechanisms are not well understood. This study evaluated the roles that the cortical face processing system, which is identified largely through studying other aspects of face perception, play in face detection. Specifically, we used functional magnetic resonance imaging (fMRI) to examine the activations of the fusifom face area (FFA), occipital face area (OFA) and superior temporal sulcus (STS) when face detection was isolated from other aspects of face perception and when face detection was perceptually-equated across individual human participants (n=20). During face detection, FFA and OFA were significantly activated, even for stimuli presented at perceptual-threshold levels, whereas STS was not. During tree detection, however, FFA and OFA were responsive only for highly salient (i.e., high contrast) stimuli. Moreover, activation of FFA during face detection predicted a significant portion of the perceptual performance levels that were determined psychophysically for each participant. This pattern of result indicates that FFA and OFA have a greater sensitivity to face detection signals and selectively support the initial process of face vs. non-face object perception. PMID:26592952

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice.

PubMed

Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

2016-02-28

To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibition of hepatic FFA influx and oxidative stress in a non-obese NASH model.

Flood Frequency Analysis using different flood descriptors - the Warsaw reach of the river Vistula case study

NASA Astrophysics Data System (ADS)

Karamuz, Emilia; Kochanek, Krzysztof; Romanowicz, Renata

2014-05-01

Flood frequency analysis (FFA) is customarily performed using annual maximum flows. However, there is a number of different flood descriptors that could be used. Among them are water levels, peaks over the threshold, flood-wave duration, flood volume, etc. In this study we compare different approaches to FFA for their suitability for flood risk assessment. The main goal is to obtain the FFA curve with the smallest possible uncertainty limits, in particular for the distribution tail. The extrapolation of FFA curves is crucial in future flood risk assessment in a changing climate. We compare the FFA curves together with their uncertainty limits obtained using flows, water levels, flood inundation area and volumes for the Warsaw reach of the river Vistula. Moreover, we derive the FFA curves obtained using simulated flows. The results are used to derive the error distribution for the maximum simulated and observed values under different modelling techniques and assess its influence on flood risk predictions for ungauged catchments. MIKE11, HEC-RAS and transfer function model are applied in average and extreme conditions to model flow propagation in the Warsaw Vistula reach. The additional questions we want to answer are what is the range of application of different modelling tools under various flow conditions and how can the uncertainty of flood risk assessment be decreased. This work was partly supported by the projects "Stochastic flood forecasting system (The River Vistula reach from Zawichost to Warsaw)" and "Modern statistical models for analysis of flood frequency and features of flood waves", carried by the Institute of Geophysics, Polish Academy of Sciences on the order of the National Science Centre (contracts Nos. 2011/01/B/ST10/06866 and 2012/05/B/ST10/00482, respectively). The water level and flow data were provided by the Institute of Meteorology and Water Management (IMGW), Poland.

Long non-coding RNA NEAT1-modulated abnormal lipolysis via ATGL drives hepatocellular carcinoma proliferation.

PubMed

Liu, Xirui; Liang, Yingjian; Song, Ruipeng; Yang, Guangchao; Han, Jihua; Lan, Yaliang; Pan, Shangha; Zhu, Mingxi; Liu, Yao; Wang, Yan; Meng, Fanzheng; Cui, Yifeng; Wang, Jiabei; Zhang, Bo; Song, Xuan; Lu, Zhaoyang; Zheng, Tongsen; Liu, Lianxin

2018-05-15

Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of the lipolytic pathway in HCC has not been elucidated. We compared levels of adipose triglyceride lipase (ATGL) in human HCC and healthy liver tissues by real time PCR, western blot and immunohistochemistry. We measured diacylglycerol(DAG) and free fatty acid (FFA) levels in HCC cells driven by the NEAT1-ATGL axis and in HCC tissues. We also assessed the effects of ATGL, DAG, FFA, and NEAT1 on HCC cells proliferation in vitro and in an orthotopic xenograft HCC mouse model. We also performed a luciferase reporter assay to investigate the interaction between NEAT1/ATGL and miR-124-3p. We found that the lipolytic enzyme, ATGL is highly expressed in human HCC tissues and predicts poor prognosis. We also found that high levels of DAG and FFA are present in HCC tissues. Furthermore, the lncRNA-NEAT1 was found to modulate ATGL expression and disrupt lipolysis in HCC cells via ATGL. Notably, ATGL and its products, DAG and FFA, were shown to be responsible for NEAT1-mediated HCC cell growth. NEAT1 regulated ATGL expression by binding miR-124-3p. Additionally, NEAT1 knockdown attenuated HCC cell growth through miR-124-3p/ATGL/DAG+FFA/PPARα signaling. Our results reveal that NEAT1-modulates abnormal lipolysis via ATGL to drive HCC proliferation.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

PubMed

Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Bifunctional heterogeneous catalysts from oil palm empty fruit bunches ash and alum for biodiesel synthesis simultaneously

NASA Astrophysics Data System (ADS)

Astar, Ismail; Usman, Thamrin; Wahyuni, Nelly; Rudiyansyah, Alimuddin, Andi Hairil

2017-03-01

Free fatty acids (FFA) contained in crude palm oil (CPO) and sludge oil has been used as the base material of biodiesel with the aid of a catalyst in the transesterification and esterification reactions. This study aims to synthesize and characterize bifunctional catalysts were synthesized from the ashes of palm empty fruit bunches (EFB) and alum based on the analysis of XRD, XRF and acidity test. Bifunctional catalyst obtained was used as a catalyst to production of biodiesel with different levels of FFA. The optimum ratio alum added was 0.2 mol at 3 hours of reaction time and 3% of catalyst by the FFA samples were used 67,40%. The catalyst with optimum alum mole variations subsequently used on samples with varying levels of FFA, namely 1.29%, 4.98%, 29.21%, 67.40% and 74.47%. Optimum conversion of methyl ester in the esterification reaction occurs in the sample with 67.40% FFA content, which reached 86.17%, while the conversion of methyl ester transesterification process optimum amounted to 45.70% in the samples with 4.98% FFA content. Methyl ester produced has a refractive index of 1.448 (29.8 ° C), density of 0.883 g / mL (25 °C) and a viscosity of 8.933 cSt (25 ° C). The results of GC-MS analysis showed that the main composition of methyl ester result of esterification of sludge oil methyl palmitate (36.84%), while the CPO transesterification shows the main composition of methyl ester is methyl oleic (38.87%). Based on the research results, the catalyst synthesized from alum and EFB ash can be used as a Bifunctional catalysts for biodiesel synthesis.

Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences.

PubMed

Wong, Alexander; Keats, Kirily; Rooney, Kieron; Hicks, Callum; Allsop, David J; Arnold, Jonathon C; McGregor, Iain S

2014-10-01

Δ(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in fat tissue where it can remain for prolonged periods. Under conditions of increased fat utilisation, blood cannabinoid concentrations can increase. However, it is unclear whether this has behavioural consequences. Here, we examined whether rats pre-treated with multiple or single doses of THC followed by a washout would show elevated plasma cannabinoids and altered behaviour following fasting or exercise manipulations designed to increase fat utilisation. Behavioural impairment was measured as an inhibition of spontaneous locomotor activity or a failure to successfully complete a treadmill exercise session. Fat utilisation was indexed by plasma free fatty acid (FFA) levels with plasma concentrations of THC and its terminal metabolite (-)-11-nor-9-carboxy-∆(9)-tetrahydrocannabinol (THC-COOH) also measured. Rats given daily THC (10 mg/kg) for 5 days followed by a 4-day washout showed elevated plasma THC-COOH when fasted for 24 h relative to non-fasted controls. Fasted rats showed lower locomotor activity than controls suggesting a behavioural effect of fat-released THC. However, rats fasted for 20 h after a single 5-mg/kg THC injection did not show locomotor suppression, despite modestly elevated plasma THC-COOH. Rats pre-treated with THC (5 mg/kg) and exercised 20 h later also showed elevated plasma THC-COOH but did not differ from controls in their likelihood of completing 30 min of treadmill exercise. These results confirm that fasting and exercise can increase plasma cannabinoid levels. Behavioural consequences are more clearly observed with pre-treatment regimes involving repeated rather than single THC dosing.

Advising an Urban FFA Chapter: A Narrative of Two Urban FFA Advisors

ERIC Educational Resources Information Center

Martin, Michael J.; Kitchel, Tracy

2015-01-01

Advising an urban FFA chapter can be a challenge for urban agriculture teachers. The contextual differences between the rural-oriented FFA and urban FFA members can make bridging the gap difficult. This narrative study sought to explore how the urban context shapes the work of an FFA chapter from the perspectives of two FFA advisors at the same…

Contrasting metabolic effects of antihypertensive agents.

PubMed

Velliquette, Rodney A; Ernsberger, Paul

2003-12-01

Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance, a comorbidity known as metabolic syndrome X. Different antihypertensives have mixed effects on these associated abnormalities. We compared three antihypertensives in the spontaneously hypertensive obese rat model of syndrome X. Moxonidine (4 mg/kg), an imidazoline and alpha2-adrenergic agonist, alpha-methyldopa (200 mg/kg), an alpha2-adrenergic agonist, or the vasodilator hydralazine (10 mg/kg) was given orally for 15 d. All three agents lowered blood pressure equally. Moxonidine significantly reduced fasting plasma insulin, glucagon, cholesterol, triglycerides, and free fatty acids (FFA) compared with untreated controls. In contrast, syndrome X markers were not affected by alpha-methyldopa treatment, and hydralazine reduced only glucagon and FFA. Relative to untreated controls, moxonidine improved glucose tolerance as shown by reduced glucose area under the curve (AUC) (13.6 +/- 2.4 versus 42.5 +/- 9.9 g x min/dl). Insulin AUC was increased (7.4 +/- 0.9 versus 3.9 +/- 1.8 microg x min/ml) as was the plasma C-peptide response to the glucose load. In contrast, alpha-methyldopa and hydralazine worsened glucose tolerance (68 +/- 26 and 110 +/- 21 g x min/ml, respectively) and significantly reduced insulin AUC (2.5 +/- 0.8 and -2.3 +/- 1.0 microg x min/ml, respectively) compared with controls. Moxonidine reduced but alpha-methyldopa and hydralazine elevated glucagon levels after the glucose load. Contrary to the "hemodynamic hypothesis" for the metabolic actions of antihypertensives, which predicts roughly equal benefits, only moxonidine had a positive impact on comorbidities. This unique action suggests a role for direct stimulation of imidazoline receptors.

Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets.

PubMed

Quarfordt, S H; Frank, A; Shames, D M; Berman, M; Steinberg, D

1970-12-01

Transport of plasma-free fatty acids (FFA) and of fatty acids in triglycerides of plasma very low density lipoproteins (VLDL-TGFA) was studied in two normal subjects, five patients with type IV hyperlipoproteinemia, and two patients with type I hyperlipoproteinemia. After intravenous pulse-labeling with albumin-bound 1-palmitate-(14)C, specific radioactivity of plasma FFA and VLDL-TGFA were determined at intervals up to 24 hr. The results were analyzed using several different multicompartmental models each compatible with the experimental data. Fractional transport of VLDL-TGFA was distinctly lower (no overlap) in the type IV patients than in the control subjects, both on a usual balanced diet (40% of calories from carbohydrate) and on a high-carbohydrate diet (80% of calories). However, net or total transport of VLDL-TGFA in the type IV patients was not clearly distinguishable from that in the control subjects, there being considerable overlap on either diet. The results suggest that in this group of type IV patients the underlying defect leading to the increased pool size of VLDL-TGFA is not overproduction but a relative defect in mechanisms for removal of VLDL-TGFA. Since some of these type IV patients had only a moderate degree of hypertriglyceridemia at the time they were studied, and since it is not established that patients with the type IV phenotype constitute a biochemically homogeneous population, the present results should not be generalized. Four studies were done (in two control subjects and two type IV patients) in which the kinetic parameters in the same individual were determined on the balanced diet and on the high-carbohydrate diet. All subjects showed an increase in VLDL-TGFA pool size. Using two of the models for analysis, all showed an increase in net transport of VLDL-TGFA; using the third model, three of the four studies showed an increase in VLDL-TGFA transport. The results are compatible with the interpretation that the carbohydrate-induced increase in VLDL-TGFA, both in controls and type IV patients, is at least in part due to an increased rate of production of VLDL-TGFA. The magnitude of the increase was approximately the same in controls and patients. Thus, metabolic adjustment to a high-carbohydrate regimen in these type IV patients may not be basically different from that in normal controls; the higher levels of VLDL-TGFA reached may simply be another reflection of a defective removal mechanism. An alternative interpretation, compatible with the data, would involve both a carbohydrate-induced increase in fractional rate of release of VLDL-TGFA from liver to plasma and a decrease in fractional removal of VLDL-TGFA from plasma without increase in net production rate. The simpler hypothesis of a single primary effect on net VLDL-TGFA production from FFA seems more likely.

Instantaneous characterization of vegetable oils via TAG and FFA profiles by easy ambient sonic-spray ionization mass spectrometry.

PubMed

Simas, Rosineide C; Catharino, Rodrigo R; Cunha, Ildenize B S; Cabral, Elaine C; Barrera-Arellano, Daniel; Eberlin, Marcos N; Alberici, Rosana M

2010-04-01

A fast and reliable method is presented for the analysis of vegetable oils. Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) is shown to efficiently desorb and ionize the main oil constituents from an inert surface under ambient conditions and to provide comprehensive triacylglyceride (TAG) and free fatty acid (FFA) profiles detected mainly as either [TAG + Na](+) or [FFA-H](-) ions. EASI(+/-)-MS analysis is simple, easily implemented, requires just a tiny droplet of the oil and is performed without any pre-separation or chemical manipulation. It also causes no fragmentation of TAG ions hence diacylglyceride (DAG) and monoacylglyceride (MAG) profiles and contents can also be measured. The EASI(+/-)-MS profiles of TAG and FFA permit authentication and quality control and can be used, for instance, to access levels of adulteration, acidity, oxidation or hydrolysis of vegetable oils in general.

A New Pain Regulatory System via the Brain Long Chain Fatty Acid Receptor GPR40/FFA1 Signal.

PubMed

Nakamoto, Kazuo

2017-01-01

An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain. It is reported that this receptor has a functional role in controlling blood glucose levels via the modulation of insulin secretion. However, its physiological function in the brain remains unknown. Our previous studies have shown that GPR40/FFA1 is expressed in pro-opiomelanocortin (POMC)-positive neurons of the arcuate nucleus, serotonergic neurons in the nucleus raphe magnus, and in noradrenergic neurons in the locus coeruleus. Furthermore, the intracerebroventricular injection of DHA or GW9508, which is a selective GPR40/FFA1 agonist, attenuates formalin-induced inflammatory pain behavior through increasing β-endorphin release in the hypothalamus. It also suppresses complete Freund's adjuvant-induced mechanical allodynia and thermal hyperalgesia. Our findings suggest that brain free long-chain fatty acids-GPR40/FFA1 signaling might have an important role in the modulation of endogenous pain control systems. In this review, I discuss the current status and our recent study regarding a new pain regulatory system via the brain long chain fatty acid receptor GPR40/FFA1 signal.

Application of GPCR Structures for Modelling of Free Fatty Acid Receptors.

PubMed

Tikhonova, Irina G

2017-01-01

Five G protein-coupled receptors (GPCRs) have been identified to be activated by free fatty acids (FFA). Among them, FFA1 (GPR40) and FFA4 (GPR120) bind long-chain fatty acids, FFA2 (GPR43) and FFA3 (GPR41) bind short-chain fatty acids and GPR84 binds medium-chain fatty acids. Free fatty acid receptors have now emerged as potential targets for the treatment of diabetes, obesity and immune diseases. The recent progress in crystallography of GPCRs has now enabled the elucidation of the structure of FFA1 and provided reliable templates for homology modelling of other FFA receptors. Analysis of the crystal structure and improved homology models, along with mutagenesis data and structure activity, highlighted an unusual arginine charge-pairing interaction in FFA1-3 for receptor modulation, distinct structural features for ligand binding to FFA1 and FFA4 and an arginine of the second extracellular loop as a possible anchoring point for FFA at GPR84. Structural data will be helpful for searching novel small-molecule modulators at the FFA receptors.

The neural code for face orientation in the human fusiform face area.

PubMed

Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan

2014-09-03

Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA. Copyright © 2014 the authors 0270-6474/14/3412155-13$15.00/0.

The Effects of Group Leader Learning Style on Student Knowledge Gain in a Leadership Camp Setting: A Repeated-Measures Experiment

ERIC Educational Resources Information Center

Brown, Nicholas R.; Terry, Robert, Jr.

2013-01-01

Many state FFA associations conduct summer camps focusing on leadership and personal development for FFA members. Interestingly, little research has been conducted on the impact or outcomes of these common activities. The purpose of this split-plot factorial repeated-measures experiment was to assess the level of campers' learning of the…

Measurement Invariance of Big-Five Factors over the Life Span: ESEM Tests of Gender, Age, Plasticity, Maturity, and La Dolce Vita Effects

ERIC Educational Resources Information Center

Marsh, Herbert W.; Nagengast, Benjamin; Morin, Alexandre J. S.

2013-01-01

This substantive-methodological synergy applies evolving approaches to factor analysis to substantively important developmental issues of how five-factor-approach (FFA) personality measures vary with gender, age, and their interaction. Confirmatory factor analyses (CFAs) conducted at the item level often do not support a priori FFA structures, due…

Influence of FFA Activities on Critical Thinking Skills in Texas Three-Star FFA Chapters

ERIC Educational Resources Information Center

Latham, Lindsey; Rayfield, John; Moore, Lori L.

2015-01-01

The purpose of this study was to determine the relationship of FFA activities on critical thinking skills of Texas FFA members in three-star FFA chapters. This descriptive study was conducted in eight purposively selected three-star FFA chapters throughout Texas. Three-star chapters are those chapters who have emerged as outstanding programs…

Effects of dietary lipid sources on performance and apparent total tract digestibility of lipids and energy when fed to nursery pigs.

PubMed

Mendoza, S M; van Heugten, E

2014-02-01

Acidulated fats and oils are by-products of the fat-refining industry. They contain high levels of FFA and are 10% to 20% less expensive than refined fats and oils. Two studies were designed to measure the effects of dietary lipid sources low or high in FFA on growth performance and apparent total tract digestibility (ATTD) of lipids and GE in nursery pigs. In Exp. 1, 189 pigs at 14 d postweaning (BW of 9.32 ± 0.11 kg) were used for 21 d with 9 replicate pens per treatment and 3 pigs per pen. Dietary treatments consisted of a control diet without added lipids and 6 diets with 6% inclusion of lipids. Four lipid sources were combined to create the dietary treatments with 2 levels of FFA (0.40% or 54.0%) and 3 degrees of fat saturation (iodine value [IV] = 77, 100, or 123) in a 2 × 3 factorial arrangement. Lipid sources were soybean oil (0.3% FFA and IV = 129.4), soybean-cottonseed acid oil blend (70.5% FFA and IV = 112.9), choice white grease (0.6% FFA and IV = 74.8), and choice white acid grease (56.0% FFA and IV = 79.0). Addition of lipid sources decreased ADFI (810 vs. 872 g/d; P = 0.018) and improved G:F (716 vs. 646 g/kg; P < 0.001). Diets high in FFA tended (P = 0.08) to improve final BW (21.35 vs. 21.01 kg) and ADG (576 vs. 560 g/d). Lipid-supplemented diets had greater ATTD of lipids than control diets (67.4% vs. 29.7%; P < 0.001). Apparent total tract digestibility of lipids was greater in diets with low FFA (69.9% vs. 64.9%; P < 0.001) and decreased linearly with increasing IV (73.2%, 69.1%, and 67.2%). For GE, ATTD was greater in diets with low FFA (83.1% vs. 80.9%; P = 0.001). In Exp. 2, 252 pigs at 7 d postweaning (BW of 7.0 ± 0.2 kg) were used for 28 d with 9 replicate pens per treatment and 4 pigs per pen. Diets included a control diet without added lipids and 6 treatments with 2.5%, 5.0%, or 7.5% of lipids from either poultry fat (1.9% FFA) or acidulated poultry fat (37.8% FFA) in a 2 × 3 factorial arrangement. Addition of lipids increased (P < 0.001) final BW (19.9 vs. 18.4 kg) and ADG (460 vs. 405 g/d) regardless of source. Fat increased (P < 0.001) ADFI when added at 2.5% and then decreased ADFI with each further increment (663, 740, 681, and 653 g for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Inclusion of lipids linearly (P < 0.001) improved G:F (615, 615, 688, and 692 g/kg for 0%, 2.5%, 5.0%, and 7.5% fat, respectively) and ATTD of lipids (17.8%, 50.2%, 71.0%, and 77.3% for 0, 2.5, 5.0, and 7.5% fat, respectively) and GE (76.1%, 76.4%, 83.3%, and 84.4% for 0%, 2.5%, 5.0%, and 7.5% fat, respectively). Acidulated lipids resulted in similar performance compared with refined lipids and could be economical alternatives to more expensive lipid sources.

Novel approach for streamflow forecasting using a hybrid ANFIS-FFA model

NASA Astrophysics Data System (ADS)

Yaseen, Zaher Mundher; Ebtehaj, Isa; Bonakdari, Hossein; Deo, Ravinesh C.; Danandeh Mehr, Ali; Mohtar, Wan Hanna Melini Wan; Diop, Lamine; El-shafie, Ahmed; Singh, Vijay P.

2017-11-01

The present study proposes a new hybrid evolutionary Adaptive Neuro-Fuzzy Inference Systems (ANFIS) approach for monthly streamflow forecasting. The proposed method is a novel combination of the ANFIS model with the firefly algorithm as an optimizer tool to construct a hybrid ANFIS-FFA model. The results of the ANFIS-FFA model is compared with the classical ANFIS model, which utilizes the fuzzy c-means (FCM) clustering method in the Fuzzy Inference Systems (FIS) generation. The historical monthly streamflow data for Pahang River, which is a major river system in Malaysia that characterized by highly stochastic hydrological patterns, is used in the study. Sixteen different input combinations with one to five time-lagged input variables are incorporated into the ANFIS-FFA and ANFIS models to consider the antecedent seasonal variations in historical streamflow data. The mean absolute error (MAE), root mean square error (RMSE) and correlation coefficient (r) are used to evaluate the forecasting performance of ANFIS-FFA model. In conjunction with these metrics, the refined Willmott's Index (Drefined), Nash-Sutcliffe coefficient (ENS) and Legates and McCabes Index (ELM) are also utilized as the normalized goodness-of-fit metrics. Comparison of the results reveals that the FFA is able to improve the forecasting accuracy of the hybrid ANFIS-FFA model (r = 1; RMSE = 0.984; MAE = 0.364; ENS = 1; ELM = 0.988; Drefined = 0.994) applied for the monthly streamflow forecasting in comparison with the traditional ANFIS model (r = 0.998; RMSE = 3.276; MAE = 1.553; ENS = 0.995; ELM = 0.950; Drefined = 0.975). The results also show that the ANFIS-FFA is not only superior to the ANFIS model but also exhibits a parsimonious modelling framework for streamflow forecasting by incorporating a smaller number of input variables required to yield the comparatively better performance. It is construed that the FFA optimizer can thus surpass the accuracy of the traditional ANFIS model in general, and is able to remove the false (inaccurately) forecasted data in the ANFIS model for extremely low flows. The present results have wider implications not only for streamflow forecasting purposes, but also for other hydro-meteorological forecasting variables requiring only the historical data input data, and attaining a greater level of predictive accuracy with the incorporation of the FFA algorithm as an optimization tool in an ANFIS model.

Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clore, J.N.; Glickman, P.S.; Helm, S.T.

1991-08-01

The authors previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent (3-3H)glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 {plus minus} 1.1 at 2430 to 8.9 {plus minus} 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200.more » The fall in Ra was associated with decreases in FFA (0.57 {plus minus} 0.10 to 0.48 {plus minus} 0.07 mM) and glycerol (0.08 {plus minus} 0.01 to 0.06 {plus minus} 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 {plus minus} 0.21 and 0.11 {plus minus} 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 {plus minus} 0.07 to 0.95 {plus minus} 0.05 mM, P less than 0.01) stimulated gluconeogenesis ((U-14C)alanine to glucose) twofold (188 {plus minus} 22% increase compared to 114 {plus minus} 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 {plus minus} 0.5 vs. 10.7 {plus minus} 0.6 mumol.kg-1.min-1) during lipid infusion.« less

Symposium review: Modulating adipose tissue lipolysis and remodeling to improve immune function during the transition period and early lactation of dairy cows.

PubMed

Contreras, G Andres; Strieder-Barboza, Clarissa; De Koster, Jenne

2018-03-01

Despite major advances in our understanding of transition and early lactation cow physiology and the use of advanced dietary, medical, and management tools, at least half of early lactation cows are reported to develop disease and over half of cow deaths occur during the first week of lactation. Excessive lipolysis, usually measured as plasma concentrations of free fatty acids (FFA), is a major risk factor for the development of displaced abomasum, ketosis, fatty liver, and metritis, and may also lead to poor lactation performance. Lipolysis triggers adipose tissue (AT) remodeling that is characterized by enhanced humoral and cell-mediated inflammatory responses and changes in its distribution of cellular populations and extracellular matrix composition. Uncontrolled AT inflammation could perpetuate lipolysis, as we have observed in cows with displaced abomasum, especially in those animals with genetic predisposition for excessive lipolysis responses. Efficient transition cow management ensures a moderate rate of lipolysis that is rapidly reduced as lactation progresses. Limiting FFA release from AT benefits immune function as several FFA are known to promote dysregulation of inflammation. Adequate formulation of pre- and postpartum diet reduces the intensity of AT lipolysis. Additionally, supplementation with niacin, monensin, and rumen-protected methyl donors (choline and methionine) during the transition period is reported to minimize FFA release into systemic circulation. Targeted supplementation of energy sources during early lactation improves energy balance and increases insulin concentration, which limits AT lipolytic responses. This review elaborates on the mechanisms by which uncontrolled lipolysis triggers inflammatory disorders. Details on current nutritional and pharmacological interventions that aid the modulation of FFA release from AT and their effect on immune function are provided. Understanding the inherent characteristics of AT biology in transition and early lactation cows will reduce disease incidence and improve lactation performance. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Metabolism pathways in chronic lymphocytic leukemia

PubMed Central

Rozovski, Uri; Hazan-Halevy, Inbal; Barzilay, Merav; Keating, Michael J.; Estrov, Zeev

2016-01-01

Alterations in CLL cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells’ metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet CLL cells’ metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase that mediates lipoprotein uptake and shifts CLL cells’ metabolism towards utilization of FFA. Herein we review the evidence for altered lipid metabolism, increased mitochondrial activity, and formation of reactive oxygen species in CLL cells, and discuss possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL. PMID:26643954

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice

PubMed Central

Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

2016-01-01

AIM: To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. CONCLUSION: These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibition of hepatic FFA influx and oxidative stress in a non-obese NASH model. PMID:26937139

Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets.

PubMed

Ulven, Trond

2012-01-01

The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets.

Carrot juice ingestion attenuates high fructose-induced circulatory pro-inflammatory mediators in weanling Wistar rats.

PubMed

Mahesh, Malleswarapu; Bharathi, Munugala; Raja Gopal Reddy, Mooli; Pappu, Pranati; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

2017-03-01

Adipose tissue, an endocrine organ, plays a vital role not only in energy homeostasis, but also in the development and/or progression of various metabolic diseases, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), via several factors and mechanisms, including inflammation. This study tested, whether carrot juice administration affected the adipose tissue development and its inflammatory status in a high fructose diet-induced rat model. For this purpose, male weanling Wistar rats were divided into four groups and fed either control or high fructose diet of AIN-93G composition with or without carrot juice ingestion for an 8 week period. Administration of carrot juice did not affect the adiposity and cell size of visceral fat depot; retroperitoneal white adipose tissue (RPWAT), which was corroborated with unaltered expression of genes involved in adipogenic and lipogenic pathways. However, it significantly reduced the high fructose diet-induced elevation of plasma free fatty acid (FFA) (P ≤ 0.05), macrophage chemoattractant protein 1 (MCP1) (P ≤ 0.01) and high sensitive C-reactive protein (hsCRP) (P ≤ 0.05) levels. Carrot juice administration attenuated the high fructose diet-induced elevation of levels of circulatory FFA and pro-inflammatory mediators; MCP1 and hsCRP without affecting the adiposity and cell size of visceral fat depot; RPWAT. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Concentrations of Plasma Free Palmitoleic and Dihomo-Gamma Linoleic Fatty Acids Are Higher in Children with Abdominal Obesity.

PubMed

Aristizabal, Juan C; González-Zapata, Laura I; Estrada-Restrepo, Alejandro; Monsalve-Alvarez, Julia; Restrepo-Mesa, Sandra L; Gaitán, Diego

2018-01-01

Increased plasma free fatty acids (FFAs) are associated with cardiometabolic risk factors in adults with abdominal obesity (AO). However, this association remains controversial in children. This study analyzed plasma FFA concentration in children with and without AO. Twenty-nine children classified with AO were matched by age and sex with 29 non-obese individuals. Blood samples were collected after fasting for 10-12 h. Plasma concentration of glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined by automatized methods. FFAs were analyzed by gas chromatography. Children with and without AO had similar age (7.1 ± 2.6 vs. 7.2 ± 2.7 years; p > 0.05) but obese children showed higher ( p < 0.05) body mass index (BMI) (+4.3 kg/m²), systolic blood pressure (+5.1 mmHg), and insulin (+27.8 pmol/L). There were no significant differences in plasma total FFA concentration between groups (1.02 ± 0.61 vs. 0.89 ± 0.37 mmol/L; p > 0.05). However, children with AO had higher palmitoleic acid (0.94 vs. 0.70 wt %; p < 0.05) and dihomo-gamma linoleic acid (DHGL) (2.76 vs. 2.07 wt %; p < 0.05). Palmitoleic and DHGL acids correlated ( p < 0.05) with BMI ( r = 0.397; r = 0.296, respectively) and with waist circumference ( r = 0.380; r = 0.276, respectively). Palmitoleic acid correlated positively with systolic blood pressure ( r = 0.386; p < 0.05) and negatively with HDL-C (-0.572; p < 0.01). In summary, children with AO have higher plasmatic concentrations of free palmitoleic and DHGL fatty acids, which correlate with cardiometabolic risk factors.

Concentrations of Plasma Free Palmitoleic and Dihomo-Gamma Linoleic Fatty Acids Are Higher in Children with Abdominal Obesity

PubMed Central

González-Zapata, Laura I.; Estrada-Restrepo, Alejandro; Monsalve-Alvarez, Julia; Restrepo-Mesa, Sandra L.; Gaitán, Diego

2018-01-01

Increased plasma free fatty acids (FFAs) are associated with cardiometabolic risk factors in adults with abdominal obesity (AO). However, this association remains controversial in children. This study analyzed plasma FFA concentration in children with and without AO. Twenty-nine children classified with AO were matched by age and sex with 29 non-obese individuals. Blood samples were collected after fasting for 10–12 h. Plasma concentration of glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined by automatized methods. FFAs were analyzed by gas chromatography. Children with and without AO had similar age (7.1 ± 2.6 vs. 7.2 ± 2.7 years; p > 0.05) but obese children showed higher (p < 0.05) body mass index (BMI) (+4.3 kg/m2), systolic blood pressure (+5.1 mmHg), and insulin (+27.8 pmol/L). There were no significant differences in plasma total FFA concentration between groups (1.02 ± 0.61 vs. 0.89 ± 0.37 mmol/L; p > 0.05). However, children with AO had higher palmitoleic acid (0.94 vs. 0.70 wt %; p < 0.05) and dihomo-gamma linoleic acid (DHGL) (2.76 vs. 2.07 wt %; p < 0.05). Palmitoleic and DHGL acids correlated (p < 0.05) with BMI (r = 0.397; r = 0.296, respectively) and with waist circumference (r = 0.380; r = 0.276, respectively). Palmitoleic acid correlated positively with systolic blood pressure (r = 0.386; p < 0.05) and negatively with HDL-C (−0.572; p < 0.01). In summary, children with AO have higher plasmatic concentrations of free palmitoleic and DHGL fatty acids, which correlate with cardiometabolic risk factors. PMID:29301242

Typical and Atypical Development of Functional Connectivity in the Face Network.

PubMed

Song, Yiying; Zhu, Qi; Li, Jingguang; Wang, Xu; Liu, Jia

2015-10-28

Extensive studies have demonstrated that face recognition performance does not reach adult levels until adolescence. However, there is no consensus on whether such prolonged improvement stems from development of general cognitive factors or face-specific mechanisms. Here, we used behavioral experiments and functional magnetic resonance imaging (fMRI) to evaluate these two hypotheses. With a large cohort of children (n = 379), we found that the ability of face-specific recognition in humans increased with age throughout childhood and into late adolescence in both face memory and face perception. Neurally, to circumvent the potential problem of age differences in task performance, attention, or cognitive strategies in task-state fMRI studies, we measured the resting-state functional connectivity (RSFC) between the occipital face area (OFA) and fusiform face area (FFA) in human brain and found that the OFA-FFA RSFC increased until 11-13 years of age. Moreover, the OFA-FFA RSFC was selectively impaired in adults with developmental prosopagnosia (DP). In contrast, no age-related changes or differences between DP and normal adults were observed for RSFCs in the object system. Finally, the OFA-FFA RSFC matured earlier than face selectivity in either the OFA or FFA. These results suggest the critical role of the OFA-FFA RSFC in the development of face recognition. Together, our findings support the hypothesis that prolonged development of face recognition is face specific, not domain general. Copyright © 2015 the authors 0270-6474/15/3514624-12$15.00/0.

FFA Leadership Handbook.

ERIC Educational Resources Information Center

Moody, Sidney B.; Miller, L. E.

The handbook is designed to assist youth leaders in the Future Farmers of America (FFA). It is organized into nine sections of varying length which consider the following facets of FFA (with sample sub-topics in parentheses): FFA members (things to know to become an effective member, membership policy); FFA officers (duties and qualifications of…

Theme: Is FFA Needed in the 21st Century?

ERIC Educational Resources Information Center

Stagg, Bill, Ed.; And Others

1999-01-01

Includes "Will FFA [Future Farmers of America] Be a Part of Agricultural Education in Twenty Years?" (Stagg, Staller); "The FFA Organization" (Vaughn, Keith, Lockaby); "FFA in Y2K=Success" (Leib); "Drivers Wanted for the 21st Century" (Morgan, Vincent); "FFA in the 21st Century" (Trivette,…

Analysis of Fundus Fluorescein Angiogram Based on the Hessian Matrix of Directional Curvelet Sub-bands and Distance Regularized Level Set Evolution.

PubMed

Soltanipour, Asieh; Sadri, Saeed; Rabbani, Hossein; Akhlaghi, Mohammad Reza

2015-01-01

This paper presents a new procedure for automatic extraction of the blood vessels and optic disk (OD) in fundus fluorescein angiogram (FFA). In order to extract blood vessel centerlines, the algorithm of vessel extraction starts with the analysis of directional images resulting from sub-bands of fast discrete curvelet transform (FDCT) in the similar directions and different scales. For this purpose, each directional image is processed by using information of the first order derivative and eigenvalues obtained from the Hessian matrix. The final vessel segmentation is obtained using a simple region growing algorithm iteratively, which merges centerline images with the contents of images resulting from modified top-hat transform followed by bit plane slicing. After extracting blood vessels from FFA image, candidates regions for OD are enhanced by removing blood vessels from the FFA image, using multi-structure elements morphology, and modification of FDCT coefficients. Then, canny edge detector and Hough transform are applied to the reconstructed image to extract the boundary of candidate regions. At the next step, the information of the main arc of the retinal vessels surrounding the OD region is used to extract the actual location of the OD. Finally, the OD boundary is detected by applying distance regularized level set evolution. The proposed method was tested on the FFA images from angiography unit of Isfahan Feiz Hospital, containing 70 FFA images from different diabetic retinopathy stages. The experimental results show the accuracy more than 93% for vessel segmentation and more than 87% for OD boundary extraction.

Analysis of Fundus Fluorescein Angiogram Based on the Hessian Matrix of Directional Curvelet Sub-bands and Distance Regularized Level Set Evolution

PubMed Central

Soltanipour, Asieh; Sadri, Saeed; Rabbani, Hossein; Akhlaghi, Mohammad Reza

2015-01-01

This paper presents a new procedure for automatic extraction of the blood vessels and optic disk (OD) in fundus fluorescein angiogram (FFA). In order to extract blood vessel centerlines, the algorithm of vessel extraction starts with the analysis of directional images resulting from sub-bands of fast discrete curvelet transform (FDCT) in the similar directions and different scales. For this purpose, each directional image is processed by using information of the first order derivative and eigenvalues obtained from the Hessian matrix. The final vessel segmentation is obtained using a simple region growing algorithm iteratively, which merges centerline images with the contents of images resulting from modified top-hat transform followed by bit plane slicing. After extracting blood vessels from FFA image, candidates regions for OD are enhanced by removing blood vessels from the FFA image, using multi-structure elements morphology, and modification of FDCT coefficients. Then, canny edge detector and Hough transform are applied to the reconstructed image to extract the boundary of candidate regions. At the next step, the information of the main arc of the retinal vessels surrounding the OD region is used to extract the actual location of the OD. Finally, the OD boundary is detected by applying distance regularized level set evolution. The proposed method was tested on the FFA images from angiography unit of Isfahan Feiz Hospital, containing 70 FFA images from different diabetic retinopathy stages. The experimental results show the accuracy more than 93% for vessel segmentation and more than 87% for OD boundary extraction. PMID:26284170

Prolonged fasting and the effects on biomarkers of inflammation and on adipokines in healthy lean men.

PubMed

van Herpen, N A; Sell, H; Eckel, J; Schrauwen, P; Mensink, R P

2013-05-01

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF)--which may positively relate to insulin resistance, and on chemerin and leptin--adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased. © Georg Thieme Verlag KG Stuttgart · New York.

Intramyocellular lipid stores increase markedly in athletes after 1.5 days lipid supplementation and are utilized during exercise in proportion to their content.

PubMed

Zehnder, Monica; Christ, Emanuel R; Ith, Michael; Acheson, Kevin J; Pouteau, Etienne; Kreis, Roland; Trepp, Roman; Diem, Peter; Boesch, Chris; Décombaz, Jacques

2006-11-01

Intramyocellular lipids (IMCL) and muscle glycogen provide local energy during exercise (EX). The objective of this study was to clarify the role of high versus low IMCL levels at equal initial muscle glycogen on fuel selection during EX. After 3 h of depleting exercise, 11 endurance-trained males consumed in a crossover design a high-carbohydrate (7 g kg(-1) day(-1)) low-fat (0.5 g kg(-1) day(-1)) diet (HC) for 2.5 days or the same diet with 3 g kg(-1) day(-1) more fat provided during the last 1.5 days of diet (four meals; HCF). Respiratory exchange, thigh muscle substrate breakdown by magnetic resonance spectroscopy, and plasma FFA oxidation ([1-(13)C]palmitate) were measured during EX (3 h, 50% W (max)). Pre-EX IMCL concentrations were 55% higher after HCF. IMCL utilization during EX in HCF was threefold greater compared with HC (P < 0.001) and was correlated with aerobic power and highly correlated (P < 0.001) with initial content. Glycogen values and decrements during EX were similar. Whole-body fat oxidation (Fat(ox)) was similar overall and plasma FFA oxidation smaller (P < 0.05) during the first EX hour after HCF. Myocellular fuels contributed 8% more to whole-body energy demands after HCF (P < 0.05) due to IMCL breakdown (27% Fat(ox)). After EX, when both IMCL and glycogen concentrations were again similar across trials, a simulated 20-km time-trial showed no difference in performance between diets. In conclusion, IMCL concentrations can be increased during a glycogen loading diet by consuming additional fat for the last 1.5 days. During subsequent exercise, IMCL decrease in proportion to their initial content, partly in exchange for peripheral fatty acids.

Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.

PubMed

Takahashi, Kaede; Fukushima, Kaori; Onishi, Yuka; Minami, Kanako; Otagaki, Shiho; Ishimoto, Kaichi; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2018-08-01

Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Free fatty acid metabolism of the human heart at rest

PubMed Central

Most, Albert S.; Brachfeld, Norman; Gorlin, Richard; Wahren, John

1969-01-01

Myocardial substrate metabolism was studied in 13 subjects at the time of diagnostic cardiac catheterization by means of palmitic acid-14C infusion with arterial and coronary sinus sampling. Two subjects were considered free of cardiac pathology and all, with one exception, demonstrated lactate extraction across the portion of heart under study. Data for this single lactate-producing subject were treated separately. The fractional extraction of 14C-labeled free fatty acids (FFA) (44.4±9.5%) was nearly twice that of unlabeled FFA (23.2±7.8%) and raised the possibility of release of FFA into the coronary sinus. FFA uptake, based on either the arterial minus coronary sinus concentration difference or the FFA-14C fractional extraction, was directly proportional to the arterial FFA concentration. Gas-liquid chromatography failed to demonstrate selective handling of any individual FFA by the heart. Fractional oxidation of FFA was 53.5±12.7%, accounting for 53.2±14.4% of the heart's oxygen consumption while nonlipid substrates accounted for an additional 30.0±17.3%. Determinations of both labeled and unlabeled triglycerides suggested utilization of this substrate by the fasting human heart. Direct measurement of FFA fractional oxidation as well as FFA uptake, exclusive of possible simultaneous FFA release, would appear necessary in studies concerned with human myocardial FFA metabolism. PMID:5794244

Factors Impacting Members Decision to Continue FFA beyond High School

ERIC Educational Resources Information Center

Sanok, Danielle E.; Stripling, Christopher T.; Stephens, Carrie A.; Griffith, Andrew P.

2015-01-01

The purpose of this study was to determine the factors influencing FFA members to continue their FFA experience beyond high school. Two focus groups were conducted, one for collegiate FFA members and one for past/current state officers. Participants provided several areas of improvement for collegiate and alumni FFA membership. Participants noted…

[Effect of FABP2 gene G54A polymorphism on lipid and glucose metabolism in simple obesity children].

PubMed

Xu, Yunpeng; Rao, Xiaojiao; Hao, Min; Hou, Lijuan; Zhu, Xiaobo; Chang, Xiaotong

2016-01-01

To explore the relationship between intestinal fatty acid binding protein (FABP2) gene G54A polymorphism and simple childhood obesity, the effect of mutant 54A FABP2 gene on serum lipids and glucose metabolism. The total of 83 subjects with overweight/obesity and 100 subjects with healthy/normal weight were involved in this study. The G54A FABP2 gene allele and genotype frequencies between control group and overweight/obesity group were detected using polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) technology, and DNA sequences were confirmed by DNA sequencing. The automatic biochemical analyzer was used to detect fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. Plasma insulin (Ins) was detected by radiation immune method, free fatty acids (FFA) was tested by ELISA method, insulin resistance index ( HOMA-IR ) was also calculated. The correlation between FABP2 G54A polymorphism and the development of children' obesity was analyzed. The relation between FABP2 G54A polymorphism and abnormal blood lipid and insulin resistance was assessed. The results of study on FABP2 gene polymorphism revealed as followed. In overweight/obese groups, the frequencies of GG, GA, AA genotypes was 33.7%, 49.4% and 16.9%, respectively. In control group, the frequencies of GG, GA, AA genotypes was 51. 0% , 40. 0% and 9. 0% , respectively. The differences between two groups was statistically significant (Χ2 = 6.27, P < 0.05). In overweight/obesity group, the frequencies of alleles were 58.4% for 54G and 41.6% for 54A. In control group, the frequencies of alleles were 71.0% for 54G and 29.0% for 54A. There was significant differences (Χ2 = 6.32, P < 0.05). The plasma biochemical variables results showed that compared with the normal control group, plasma TG (P < 0.01), Ins (P < 0.05), HOMA-IR (P < 0.05) were elevated in overweight/obesity group, the difference between two groups was statistically significant. At the same time, in overweight/obesity group, the carriers of AA homozygous genotypes had significantly higher plasma TG levels than those with GG wild genotypes (P < 0.05). A increased tendency of plasma Ins, FFA levels and HOMA-IR was found in the carriers with AA homozygous genotypes, but no differences compared with those with GG wild genotypes. Compared with those with GG wild genotypes, related plasma biochemical variables in the carriers with GA heterozygous genotypes had no differences (P > 0.05). The FABP2 gene G54A polymorphism is related to simple children obesity and lipid metabolism abnormality. The allele encoding in FABP2 gene may be a potential factor contributing to promoting lipid metabolism abnormality of and insulin resistance.

Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

PubMed Central

Ulven, Trond

2012-01-01

The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets. PMID:23060857

Critical Theory View of the National FFA Convention

ERIC Educational Resources Information Center

Martin, Michael J.; Kitchel, Tracy

2015-01-01

Urban FFA members face unique challenges if they want to become active members in the National FFA Organization. FFA leaders have realized that the FFA organization does not represent the evolving demographics of America and have made efforts to cater to urban and diverse high school audiences with some success. This study seeks to explore this…

[Evaluation of myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP)].

PubMed

Momose, M; Kobayashi, H; Saito, K; Matsumoto, N; Maki, M; Hosoda, S; Kusakabe, K

1994-12-01

To evaluate the myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), nineteen patients with ischemic heart disease including left ventricular hypertrophy (mean age 63 +/- 7.8, 14 males and 5 females) underwent BMIPP myocardial scintigraphy. Myocardial uptake (MU) of BMIPP to the total injected dose was calculated from anterior view of the planar image in all subjects, and was compared with plasma glucose (BS), triglyceride (TG), and free fatty acid (FFA). It was also compared with left ventricular mass (LVM) calculated with echocardiography. MU was not related to BS, TG, and FFA, however had the positive correlation with LVM (r = 0.676, p < 0.01). Myocardial uptake per left ventricular mass (MU/LVM) had the negative correlation with LVM (r = -0.671, p < 0.01). Further studies for the significance of MU/LVM will be required.

Winning the War: A Historical Analysis of the FFA during World War II

ERIC Educational Resources Information Center

Wolf, Kattlyn J.; Connors, James J.

2009-01-01

The United States' participation in World War II affected millions of men, women, and children, both at home and around the world. The war effort also affected the Future Farmers of America (FFA). FFA members, agriculture teachers, and national FFA officers all volunteered to serve their country during the war. Local FFA chapters and individual…

Physiological Effects of Free Fatty Acid Production in Genetically Engineered Synechococcus elongatus PCC 7942

PubMed Central

Ruffing, Anne M.; Jones, Howland D.T.

2012-01-01

The direct conversion of carbon dioxide into biofuels by photosynthetic microorganisms is a promising alternative energy solution. In this study, a model cyanobacterium, Synechococcus elongatus PCC 7942, is engineered to produce free fatty acids (FFA), potential biodiesel precursors, via gene knockout of the FFA-recycling acyl-ACP synthetase and expression of a thioesterase for release of the FFA. Similar to previous efforts, the engineered strains produce and excrete FFA, but the yields are too low for large-scale production. While other efforts have applied additional metabolic engineering strategies in an attempt to boost FFA production, we focus on characterizing the engineered strains to identify the physiological effects that limit cell growth and FFA synthesis. The strains engineered for FFA-production show reduced photosynthetic yields, chlorophyll-a degradation, and changes in the cellular localization of the light-harvesting pigments, phycocyanin and allophycocyanin. Possible causes of these physiological effects are also identified. The addition of exogenous linolenic acid, a polyunsaturated FFA, to cultures of S. elongatus 7942 yielded a physiological response similar to that observed in the FFA-producing strains with only one notable difference. In addition, the lipid constituents of the cell and thylakoid membranes in the FFA-producing strains show changes in both the relative amounts of lipid components and the degree of saturation of the fatty acid side chains. These changes in lipid composition may affect membrane integrity and structure, the binding and diffusion of phycobilisomes, and the activity of membrane-bound enzymes including those involved in photosynthesis. Thus, the toxicity of unsaturated FFA and changes in membrane composition may be responsible for the physiological effects observed in FFA-producing S. elongatus 7942. These issues must be addressed to enable the high yields of FFA synthesis necessary for large-scale biofuel production. PMID:22473793

Comparison of systemic cytokine responses after a long distance triathlon and a 100-km run: relationship to metabolic and inflammatory processes.

PubMed

Gomez-Merino, Danielle; Drogou, Catherine; Guezennec, Charles Yannick; Burnat, Pascal; Bourrilhon, Cyprien; Tomaszewski, Armand; Milhau, Stéphane; Chennaoui, Mounir

2006-06-01

Suggested mechanisms for the systemic, circulating cytokinemia observed during heavy physical exertion include inflammation and energy demand. We compared cytokine levels and examined the underlying physiological mechanisms between a long-distance triathlon and a 100-km run, two endurance races of similar duration but characterized by differences in muscle strain. Blood samples were collected from 12 triathletes (34.8 +/- 1.4 yr) and 11 runners (42.4 +/- 2.2 yr) the day before and at the end of races (T1, R1), and 24 h and 7 days post-race (R2, R3). At R1, significant race-related differences were observed, with greater increases in plasma levels of interleukins (IL)-6, IL-1ra, and IL-10 in the triathletes than in the runners, while levels of the chemokine IL-8 increased solely in the runners (P < 0.05, P < 0.05, P < 0.01, and P < 0.001, respectively). At R1, free fatty acid (FFA) levels were 119% higher in the triathletes than in the runners, who were the most liable to muscle damage in view of increased levels of the muscle-specific enzyme, creatine kinase (CK), loss of muscle flexibility and decreased physical performance. At R1, levels of heat shock protein (HSP)72 increased in the two groups but were 173% higher in the runners. For the two groups, all parameters had returned to pre-race levels by seven days post-race. Positive correlations were noted between IL-6 and FFA in the triathletes and between IL-8 and CK and HSP72 in the runners. The differences between cytokine responses after a long distance triathlon and a 100-km run suggested that IL-6 and IL-8 could be employed as respective markers of the intensity of the muscular activity required for substrate availability and vascular inflammation.

Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2.

PubMed

Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

2016-03-01

Furfuryl alcohol (FFA) is a carcinogenic food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. The activation by sulfotransferases (SULTs) yields a DNA reactive and mutagenic sulfate ester. The most prominent DNA adduct, N(2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N(2)-MF-dG), was detected in FFA-treated mice and also in human tissue samples. The dominant pathway of FFA detoxification is the oxidation via alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). The activity of these enzymes may be greatly altered in the presence of inhibitors or competitive substrates. Here, we investigated the impact of ethanol and the ADH inhibitor 4-methylpyrazole (4MP) on the DNA adduct formation by FFA in wild-type and in humanized mice that were transgenic for human SULT1A1/1A2 and deficient in the mouse (m) Sult1a1 and Sult1d1 genes (h1A1/1A2/1a1(-)/1d1(-)). The administration of FFA alone led to hepatic adduct levels of 4.5 N(2)-MF-dG/10(8) nucleosides and 33.6 N(2)-MF-dG/10(8) nucleosides in male and female wild-type mice, respectively, and of 19.6 N(2)-MF-dG/10(8) nucleosides and 95.4 N(2)-MF-dG/10(8) nucleosides in male and female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 1.6g ethanol/kg body weight increased N(2)-MF-dG levels by 2.3-fold in male and by 1.7-fold in female wild-type mice and by 2.5-fold in male and by 1.5-fold in female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 100mg 4MP/kg body weight had a similar effect on the adduct levels. These findings indicate that modulators of the oxidative metabolism, e.g. the drug 4MP or consumption of alcoholic beverages, may increase the genotoxic effects of FFA also in humans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines.

PubMed

Suckow, Arthur T; Briscoe, Celia P

2017-01-01

The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans. Expression profiling, the phenotyping of FFA receptor knockout mice, and the results of studies exploring the effects of these ligands in rodents have uncovered a number of indications where engagement of one or a combination of FFA receptors might provide some clinical benefit in areas including diabetes, inflammatory bowel syndrome, Alzheimer's, pain, and cancer. In this chapter, we will review the clinical potential of modulating FFA receptors based on preclinical and in some cases clinical studies with synthetic ligands. In particular, key aspects and challenges associated with small-molecule ligand identification and FFA receptor pharmacology will be addressed with a view of the hurdles that need to be overcome to fully understand the potential of the receptors as therapeutic targets.

Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase.

PubMed

Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

2014-09-05

Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL. Copyright © 2014 Elsevier Inc. All rights reserved.

Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

PubMed

Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

2010-09-01

Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright 2010 Physicians Postgraduate Press, Inc.

Position related analysis of the appearance of and relationship between post-match physical and mental fatigue in university rugby football players.

PubMed

Mashiko, T; Umeda, T; Nakaji, S; Sugawara, K

2004-10-01

The relationship between physical and mental fatigue in rugby players after a match was examined, taking into account the position played. The Profile of Mood State (POMS) test, blood biochemical parameters, and serum opsonic activity were measured for 37 university rugby football players before and after a match. There were no differences in parameter changes except for blood urea nitrogen (a marker for protein catabolism) between the forwards and the backs. Regarding correlation between physical and mental fatigue, in forwards, changes in POMS scores showed a positive correlation with changes in the levels of enzymes of skeletal muscle origin, such as glutamate oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH), and free fatty acid (FFA) level and white blood cell count (for example, in the Total Mood Disturbance (TMD) score, Spearman's correlation coefficient was 0.417 and p<0.05 with GOT, 0.413 and p<0.05 with LDH, 0.462 and p<0.05 with FFA, and 0.442 and p<0.05 with white blood cell count). In backs, changes in the POMS scores showed a positive correlation with changes in the levels of lipid related parameters such as FFA and total cholesterol (for example, as regards the TMD score, Spearman's correlation coefficient was 0.481 and p<0.05 with FFA, and 0.550 and p<0.05 with total cholesterol), and showed a negative correlation with change in blood glucose level (TMD score, -0.517 and p<0.05). The different exercise loading of the position played during a rugby match may cause differences in the relationship between physical and mental fatigue.

Arsenic-induced dyslipidemia in male albino rats: comparison between trivalent and pentavalent inorganic arsenic in drinking water.

PubMed

Afolabi, Olusegun K; Wusu, Adedoja D; Ogunrinola, Olabisi O; Abam, Esther O; Babayemi, David O; Dosumu, Oluwatosin A; Onunkwor, Okechukwu B; Balogun, Elizabeth A; Odukoya, Olusegun O; Ademuyiwa, Oladipo

2015-06-05

Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. However, the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic. In order to investigate the effects of inorganic arsenic exposure on lipid metabolism, male albino rats were exposed to 50, 100 and 150 ppm arsenic as sodium arsenite and 100, 150 and 200 ppm arsenic as sodium arsenate respectively in their drinking water for 12 weeks. Dyslipidemia induced by the two arsenicals exhibited different patterns. Hypocholesterolemia characterised the effect of arsenite at all the doses, but arsenate induced hypercholesterolemia at the 150 ppm As dose. Hypertriglyceridemia was the hallmark of arsenate effect whereas plasma free fatty acids (FFAs) was increased by the two arsenicals. Reverse cholesterol transport was inhibited by the two arsenicals as evidenced by decreased HDL cholesterol concentrations whereas hepatic cholesterol was increased by arsenite (100 ppm As), but decreased by arsenite (150 ppm As) and arsenate (100 ppm As) respectively. Brain cholesterol and triglyceride were decreased by the two arsenicals; arsenate decreased the renal content of cholesterol, but increased renal content of triglyceride. Arsenite, on the other hand, increased the renal contents of the two lipids. The two arsenicals induced phospholipidosis in the spleen. Arsenite (150 ppm As) and arsenate (100 ppm As) inhibited hepatic HMG CoA reductase. At other doses of the two arsenicals, hepatic activity of the enzyme was up-regulated. The two arsenicals however up-regulated the activity of the brain enzyme. We observed positive associations between tissue arsenic levels and plasma FFA and negative associations between tissue arsenic levels and HDL cholesterol. Our findings indicate that even though sub-chronic exposure to arsenite and arsenate through drinking water produced different patterns of dyslipidemia, our study identified two common denominators of dyslipidemia namely: inhibition of reverse cholesterol transport and increase in plasma FFA. These two denominators (in addition to other individual perturbations of lipid metabolism induced by each arsenical), suggest that in contrast to strengthening a dose-dependent effect phenomenon, the two forms of inorganic arsenic induced lipotoxic and non-lipotoxic dyslipidemia at "low" or "medium" doses and these might be responsible for the cardiovascular and other disease endpoints of inorganic arsenic exposure through drinking water.

The α' subunit of β-conglycinin and the A1-5 subunits of glycinin are not essential for many hypolipidemic actions of dietary soy proteins in rats.

PubMed

Chen, Qixuan; Wood, Carla; Gagnon, Christine; Cober, Elroy R; Frégeau-Reid, Judith A; Gleddie, Stephen; Xiao, Chao Wu

2014-08-01

This study examined the effects of dietary soy protein (SP) lacking different storage protein subunits and isoflavones (ISF) on the abdominal fat, blood lipids, thyroid hormones, and enzymatic activities in rats. Weanling Sprague-Dawley rats (8 males and 8 females/group) were fed diets containing either 20 % casein without or with supplemental isoflavones or alcohol-washed SP isolate or SP concentrates (SPC) prepared from 6 different soy bean lines for 8 weeks. Feeding of diets containing SPC regardless of their subunit compositions significantly lowered relative liver weights, blood total, free, and LDL cholesterol in both genders (P < 0.05) and also reduced serum free fatty acids (FFA) and abdominal fat in females (P < 0.05) compared to the casein or casein + ISF diets. Dietary SPC significantly elevated the plasma free triiodothyronine (T3) in both genders and total T3 in females compared to the casein diet (P < 0.05). The SPC lacking β-conglycinin α' and either the glycinin A1-3 or A1-5 subunits increased total T3 in males and reduced plasma enzymatic activities of creatine kinase and lactate dehydrogenase compared to casein or casein + ISF diet (P < 0.05). Soy isoflavones were mainly responsible for the hypocholesterolemic effects and increased plasma free T3, whereas reduction in FFA, abdominal fat, liver weight and increased plasma total T3 were the effects of the soy proteins. Neither the α' subunit of β-conglycinin nor the A1-5 subunits of glycinin are essential for the hypolipidemic properties of soy proteins.

The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism.

PubMed

Hudson, Brian D; Shimpukade, Bharat; Mackenzie, Amanda E; Butcher, Adrian J; Pediani, John D; Christiansen, Elisabeth; Heathcote, Helen; Tobin, Andrew B; Ulven, Trond; Milligan, Graeme

2013-11-01

TUG-891 [3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein-coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA α-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca²⁺ mobilization, β-arrestin-1 and β-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca²⁺ signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4.

Obstructive sleep apnea and obesity are associated with reduced GPR 120 plasma levels in children.

PubMed

Gozal, David; Kheirandish-Gozal, Leila; Carreras, Alba; Khalyfa, Abdelnaby; Peris, Eduard

2014-05-01

Obstructive sleep apnea (OSA) is a common health problem, particularly in obese children, in whom a vicious cycle of obesity and OSA interdependencies promotes increased food intake. G protein-coupled receptor 120 (GPR 120) is a long-chain free fatty acid (FFA) receptor that plays an important role in energy homeostasis, and protects against insulin resistance and systemic inflammation. We hypothesized that GPR 120 levels would be reduced in children with OSA, particularly among obese children. Cross-sectional prospectively recruited cohort. Academic pediatric sleep program. Two hundred twenty-six children (mean age: 7.0 ± 2.1 y) underwent overnight polysomnographic evaluation and a fasting blood draw the morning after the sleep study. In addition to lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hsCRP) assays, monocyte GPR 120 expression, and plasma GPR 120 levels were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay kits. Obese children and those with OSA had significantly lower GPR 120 monocyte expression and plasma GPR 120 levels. Furthermore, when both obesity and OSA were present, GPR 120 levels were lowest. Linear associations emerged between GPR 120 plasma levels and body mass index (BMI) z score, as well as with apnea-hypopnea index (AHI), saturation of peripheral oxygen (SpO2) nadir, and respiratory arousal index (RAI), with RAI remaining statistically significant when controlling for age, ethnicity, sex, and BMI z score (P < 0.001). Similarly, HOMA-IR was significantly associated with GPR 120 levels, but neither low density lipoprotein nor high density lipoprotein cholesterol or hsCRP levels exhibited significant correlations. G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric OSA and obesity (particularly when both are present) and may play a role in modulating the degree of insulin resistance. The short- and long-term significance of reduced GPR 120 relative to food intake and glycemic deregulation remains undefined.

Effects of exercise at individual anaerobic threshold and maximal fat oxidation intensities on plasma levels of nesfatin-1 and metabolic health biomarkers.

PubMed

Mohebbi, Hamid; Nourshahi, Maryam; Ghasemikaram, Mansour; Safarimosavi, Saleh

2015-03-01

Exercise is recognized as an effective method of weight management and short-term appetite regulation tool. The effect of different exercise intensities on appetite regulation hormones in healthy overweight participants has not been intensively studied. The aim of this study was to examine the influence of exercise at individual anaerobic threshold (IAT) and maximal fat oxidation (Fatmax) intensities on the nesfatin-1 response and metabolic health biomarkers in overweight men. Nine healthy overweight males (age, 23.1 ± 1.1 years) volunteered in this study in a counterbalanced order. Blood samples were obtained before, immediately after, and following the first 45 min of recovery for measuring plasma variables. There was significant decrease in plasma levels of nesfatin-1 and leptin after exercise at the IAT intensity which remained lower than baseline following 45 min of recovery. However, nesfatin-1 and leptin levels did not change significantly in any time courses of Fatmax intensity (P > 0.09). Plasma interleukin-6 (IL-6) concentration increased during exercise in both intensities (P < 0.05), whereas changes in free fatty acids (FFAs) and epinephrine concentrations were significant only at the IAT. In addition, a significant correlation was found among nesfatin-1 levels with insulin (r = 0.39, P < 0.05) and glucose (r = 0.41, P < 0.05) at basal and in response to exercise. These results indicate that IAT has a greater exercise-induced appetite regulation effect compared with Fat(max). Based on these data, the intensity of exercise may have an important role in changes of nesfatin-1, leptin, FFA, and epinephrine concentrations even though this was not the case for IL-6 and insulin resistance.

Cortical Thickness in Fusiform Face Area Predicts Face and Object Recognition Performance

PubMed Central

McGugin, Rankin W.; Van Gulick, Ana E.; Gauthier, Isabel

2016-01-01

The fusiform face area (FFA) is defined by its selectivity for faces. Several studies have shown that the response of FFA to non-face objects can predict behavioral performance for these objects. However, one possible account is that experts pay more attention to objects in their domain of expertise, driving signals up. Here we show an effect of expertise with non-face objects in FFA that cannot be explained by differential attention to objects of expertise. We explore the relationship between cortical thickness of FFA and face and object recognition using the Cambridge Face Memory Test and Vanderbilt Expertise Test, respectively. We measured cortical thickness in functionally-defined regions in a group of men who evidenced functional expertise effects for cars in FFA. Performance with faces and objects together accounted for approximately 40% of the variance in cortical thickness of several FFA patches. While subjects with a thicker FFA cortex performed better with vehicles, those with a thinner FFA cortex performed better with faces and living objects. The results point to a domain-general role of FFA in object perception and reveal an interesting double dissociation that does not contrast faces and objects, but rather living and non-living objects. PMID:26439272

Albumin-associated free fatty acids induce macropinocytosis in podocytes

PubMed Central

Chung, Jun-Jae; Huber, Tobias B.; Gödel, Markus; Jarad, George; Hartleben, Björn; Kwoh, Christopher; Keil, Alexander; Karpitskiy, Aleksey; Hu, Jiancheng; Huh, Christine J.; Cella, Marina; Gross, Richard W.; Miner, Jeffrey H.; Shaw, Andrey S.

2015-01-01

Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria. PMID:25915582

Horizontal tuning for faces originates in high-level Fusiform Face Area.

PubMed

Goffaux, Valerie; Duecker, Felix; Hausfeld, Lars; Schiltz, Christine; Goebel, Rainer

2016-01-29

Recent work indicates that the specialization of face visual perception relies on the privileged processing of horizontal angles of facial information. This suggests that stimulus properties assumed to be fully resolved in primary visual cortex (V1; e.g., orientation) in fact determine human vision until high-level stages of processing. To address this hypothesis, the present fMRI study explored the orientation sensitivity of V1 and high-level face-specialized ventral regions such as the Occipital Face Area (OFA) and Fusiform Face Area (FFA) to different angles of face information. Participants viewed face images filtered to retain information at horizontal, vertical or oblique angles. Filtered images were viewed upright, inverted and (phase-)scrambled. FFA responded most strongly to the horizontal range of upright face information; its activation pattern reliably separated horizontal from oblique ranges, but only when faces were upright. Moreover, activation patterns induced in the right FFA and the OFA by upright and inverted faces could only be separated based on horizontal information. This indicates that the specialized processing of upright face information in the OFA and FFA essentially relies on the encoding of horizontal facial cues. This pattern was not passively inherited from V1, which was found to respond less strongly to horizontal than other orientations likely due to adaptive whitening. Moreover, we found that orientation decoding accuracy in V1 was impaired for stimuli containing no meaningful shape. By showing that primary coding in V1 is influenced by high-order stimulus structure and that high-level processing is tuned to selective ranges of primary information, the present work suggests that primary and high-level levels of the visual system interact in order to modulate the processing of certain ranges of primary information depending on their relevance with respect to the stimulus and task at hand. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nonoxidative free fatty acid disposal is greater in young women than men.

PubMed

Koutsari, Christina; Basu, Rita; Rizza, Robert A; Nair, K Sreekumaran; Khosla, Sundeep; Jensen, Michael D

2011-02-01

Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. We measured: systemic FFA turnover using a continuous iv infusion of [9-10, (3)H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. the study was conducted at the Mayo Clinic General Clinical Research Center. Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). There were no interventions. Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities.

Evaluation of the National FFA Nominating Committee Training

ERIC Educational Resources Information Center

Bruce, Jacklyn; Ricketts, Kristina

2007-01-01

The purpose of this qualitative study was to evaluate if the environment of the National FFA Organization's Nominating Committee training fosters transfer of training to the job they are required to perform, selecting National FFA Officers. Nominating Committee members, advisors, National FFA staff, and National Officer candidates participated in…

Neural codes of seeing architectural styles

PubMed Central

Choo, Heeyoung; Nasar, Jack L.; Nikrahei, Bardia; Walther, Dirk B.

2017-01-01

Images of iconic buildings, such as the CN Tower, instantly transport us to specific places, such as Toronto. Despite the substantial impact of architectural design on people’s visual experience of built environments, we know little about its neural representation in the human brain. In the present study, we have found patterns of neural activity associated with specific architectural styles in several high-level visual brain regions, but not in primary visual cortex (V1). This finding suggests that the neural correlates of the visual perception of architectural styles stem from style-specific complex visual structure beyond the simple features computed in V1. Surprisingly, the network of brain regions representing architectural styles included the fusiform face area (FFA) in addition to several scene-selective regions. Hierarchical clustering of error patterns further revealed that the FFA participated to a much larger extent in the neural encoding of architectural styles than entry-level scene categories. We conclude that the FFA is involved in fine-grained neural encoding of scenes at a subordinate-level, in our case, architectural styles of buildings. This study for the first time shows how the human visual system encodes visual aspects of architecture, one of the predominant and longest-lasting artefacts of human culture. PMID:28071765

Neural codes of seeing architectural styles.

PubMed

Choo, Heeyoung; Nasar, Jack L; Nikrahei, Bardia; Walther, Dirk B

2017-01-10

Images of iconic buildings, such as the CN Tower, instantly transport us to specific places, such as Toronto. Despite the substantial impact of architectural design on people's visual experience of built environments, we know little about its neural representation in the human brain. In the present study, we have found patterns of neural activity associated with specific architectural styles in several high-level visual brain regions, but not in primary visual cortex (V1). This finding suggests that the neural correlates of the visual perception of architectural styles stem from style-specific complex visual structure beyond the simple features computed in V1. Surprisingly, the network of brain regions representing architectural styles included the fusiform face area (FFA) in addition to several scene-selective regions. Hierarchical clustering of error patterns further revealed that the FFA participated to a much larger extent in the neural encoding of architectural styles than entry-level scene categories. We conclude that the FFA is involved in fine-grained neural encoding of scenes at a subordinate-level, in our case, architectural styles of buildings. This study for the first time shows how the human visual system encodes visual aspects of architecture, one of the predominant and longest-lasting artefacts of human culture.

Synthesis of solid catalyst from egg shell waste and clay for biodiesel production

NASA Astrophysics Data System (ADS)

Setiadji, S.; Sundari, C. D. D.; Munir, M.; Fitriyah, S.

2018-05-01

Until now, energy consumption in Indonesia is almost entirely fulfilled by fossil fuels, thus, its availability will be limited and continue to decrease. To overcome these problems, development and utilization of renewable energy are required, one of which is biodiesel. Biodiesel can be prepared through transesterification reaction of vegetable oil using catalyst. In this research, a solid catalyst for biodiesel synthesis was prepared from chicken egg shell waste and clay. Optimization of the transesterification reaction of coconut (Cocos nucifera) oil to obtain biodiesel was also carried out. The formation of CaO/kaolin catalyst was confirmed based on the results of XRD and SEM-EDS. This catalyst is suitable for biodiesel synthesis from vegetable oils with lower FFA (free fatty acid) levels, i.e. coconut oil with FFA level of 0.18%. Based on FTIR result, FFA level and flame tests, it was found that biodiesel was successfully formed. Synthesis of biodiesel has the optimum conditions on reaction time of 16 hours and temperature of 64 °C, with oil: methanol ratio of 1: 15 and CaO/kaolin catalyst concentration of 0.9% in a reflux system.

Lepidium peruvianum chacon restores homeostasis impaired by restraint stress.

PubMed

López-Fando, A; Gómez-Serranillos, M P; Iglesias, I; Lock, O; Upamayta, U P; Carretero, M E

2004-06-01

Lepidium peruvianum root has been traditionally utilized by native Peruvians, since before the time of the Incas, for both nutritional and putative medicinal purposes as an adaptogen and also to enhance fertility in humans and animals. The present research was conducted to evaluate the anti-stress activity of the methanolic extract of Lepidium peruvianum. The drug is capable of attenuating or even eliminating variations in homeostasis produced by stress since it reduces or abolishes stress-induced ulcers, elevated corticosterone levels, the reduction of glucose and the increase in the weight of adrenal glands produced by stress. It also eliminates the decrease in free fatty-acids (FFA) in plasma produced by stress and we obtain a positive result in the forced-swimming test. Thus, it did not appear to affect restraint stress-induced immunosuppression.

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals.

PubMed

Giacco, R; Clemente, G; Luongo, D; Lasorella, G; Fiume, I; Brouns, F; Bornet, F; Patti, L; Cipriano, P; Rivellese, A A; Riccardi, G

2004-06-01

The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. A randomized double-blind sequential cross-over study. Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02). A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

Effect of seabuckthorn leaf extracts on circulating energy fuels, lipid peroxidation and antioxidant parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery.

PubMed

Saggu, Shalini; Kumar, Ratan

2008-06-01

The present study was carried out to study mechanism of adaptogenic activity of seabuckthorn leaf extract, administered orally in rats both in single and five doses at a dose of 100mg/kg body weight 30min prior to C-H-R exposure. The efficacy of the extract was studied on circulating energy fuels, lipid peroxidation and anti-oxidant parameters in rats on attaining the T(rec) 23 degrees C during C-H-R exposure and after recovery (T(rec) 37 degrees C) from C-H-R induced hypothermia. Single dose treatment in rats restricted rise in blood malondialdehyde (MDA) levels and decrease in glutathione (GSH) and catalase (CAT) levels. Both single and five doses also restricted the rise in serum free fatty acids (FFA) and lactate dehydrogenase (LDH) levels on attaining T(rec) 23 degrees C during C-H-R exposure, suggesting more efficient utilization of FFA for energy production and better maintained cell membrane permeability. This suggested that the adaptogenic activity of the extract might be due to its anti-oxidative activity, maintained blood glucose levels, better utilization of FFA and improved cell membrane permeability.

Effects of indigestible carbohydrates in barley on glucose metabolism, appetite and voluntary food intake over 16 h in healthy adults.

PubMed

Johansson, Elin V; Nilsson, Anne C; Östman, Elin M; Björck, Inger M E

2013-04-11

Recent knowledge in animals suggests that gut microbial metabolism may affect host metabolism, including appetite regulating hormones. The aim of the present study was to evaluate the potential effects of a whole grain barley kernel product, rich in intrinsic indigestible carbohydrates (dietary fibre and resistant starch), on markers of metabolism and appetite regulation in healthy subjects. Boiled barley kernels (BK) or white wheat bread (WWB; reference) were provided as late evening meals to 19 young adults in random order using a cross-over design. During subsequent ad libitum standardized breakfast and lunch meals (10.5-16 h), blood was collected for analysis of glucose, plasma insulin, adiponectin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), serum free fatty acids (FFA) and interleukin (IL)-6. In addition, appetite sensations, voluntary energy intake and breath H2 were determined. BK as evening meal increased plasma GLP-1 at fasting (P < 0.05) and during the experimental day (P < 0.01) compared with WWB. In addition the BK evening meal decreased fasting serum FFA (P < 0.05) and tended to decrease fasting serum IL-6 (P = 0.06). At lunch, preceded by BK evening meal, voluntary energy intake was decreased (P < 0.05) when compared to WWB evening meal. The BK evening meal decreased incremental blood glucose area (P < 0.01), promoted higher breath H2 (P < 0.001), maintained adiponectin concentrations (P < 0.05) and reduced perceived hunger (P < 0.05) during 10.5-16 h after the meal. The results indicate that the BK evening meal, facilitate glucose regulation, increase the release of GLP-1, reduce subsequent energy intake while at the same time decreasing hunger over 2 subsequent meals, and reduce fasting FFA the subsequent morning, possibly mediated through gut microbial fermentation of the indigestible carbohydrates.

FFA4 receptor (GPR120): A hot target for the development of anti-diabetic therapies.

PubMed

Liu, Hong-Da; Wang, Wen-bo; Xu, Zhi-gang; Liu, Chang-hong; He, Dong-fang; Du, Lv-Pei; Li, Min-Yong; Yu, Xiao; Sun, Jin-peng

2015-09-15

Free Fatty Acid 4 receptor (FFA4 receptor or GPR120), a rhodopsin-like G protein coupled receptor (GPCR) subfamily member, is a receptor that senses specific fatty acids such as ω-3 fatty acid in fish oil or the endogenous signaling lipid, PHASA. FFA4 receptor is enriched in lung, colon and adipose tissue but is also detected in many other tissues and cells. The activation of FFA4 receptor has multiple effects, including but not limited to inhibition of inflammation, improving insulin sensitivity and adipogenesis, and regulating hormone secretion from the gastro-intestinal system and pancreatic islets. The important role of FFA4 receptor in maintaining metabolic homeostasis strongly indicates the great potential of selective FFA4 receptor agonizts to treat diabetes and inflammation. In this review, we summarize recent research progress in the physiological and biochemical studies of FFA4 receptor and highlight its underlying signaling mechanisms and ligand identification to assist future research to exploit FFA4 receptor as a drug target. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the Contribution of Signals Originating from Large Blood Vessels to Signals of Functionally Specific Brain Areas

PubMed Central

Chung, Jun-Young; Ogawa, Seiji

2015-01-01

The fusiform face area (FFA) is known to play a pivotal role in face processing. The FFA is located in the ventral region, at the base of the brain, through which large blood vessels run. The location of the FFA via functional MRI (fMRI) may be influenced by these large blood vessels. Responses of large blood vessels may not exactly correspond to neuronal activity in a target area, because they may be diluted and influenced by inflow effects. In this study, we investigated the effects of large blood vessels in the FFA, that is, whether the FFA includes large blood vessels and/or whether inflow signals contribute to fMRI signals of the FFA. For this purpose, we used susceptibility-weighted imaging (SWI) sequences to visualize large blood vessels and dual-echo gradient-echo echo-planar imaging (GE-EPI) to measure inflow effects. These results showed that the location and response signals of the FFA were not influenced by large blood vessels or inflow effects, although large blood vessels were located near the FFA. Therefore, the data from the FFA obtained by individual analysis were robust to large blood vessels but leaving a warning that the data obtained by group analysis may be prone to large blood vessels. PMID:26413511

Short-chain fatty acid sensing in rat duodenum.

PubMed

Akiba, Yasutada; Inoue, Takuya; Kaji, Izumi; Higashiyama, Masaaki; Narimatsu, Kazuyuki; Iwamoto, Ken-ichi; Watanabe, Masahiko; Guth, Paul H; Engel, Eli; Kuwahara, Atsukazu; Kaunitz, Jonathan D

2015-02-01

Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5-HT. The effects of luminal short-chain fatty acids (SCFAs) in the foregut are unknown. Free fatty acid receptors (FFARs) for long-chain fatty acids (LCFAs) and SCFAs are expressed in enteroendocrine cells. SCFA receptors, termed FFA2 and FFA3, are expressed in duodenal enterochromaffin cells and L cells, respectively. Activation of LCFA receptor (FFA1) and presumed FFA3 stimulates duodenal HCO3(-) secretion via a glucagon-like peptide (GLP)-2 pathway, whereas FFA2 activation induces HCO3(-) secretion via muscarinic and 5-HT4 receptor activation. The presence of SCFA sensing in the duodenum with GLP-2 and 5-HT signals further supports the hypothesis that luminal SCFA in the foregut may contribute towards the generation of functional symptoms. Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3(-) secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3(-) exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3(-) exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

The triglyceride-lowering effect of supplementation with dual probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032: Reduction of fasting plasma lysophosphatidylcholines in nondiabetic and hypertriglyceridemic subjects.

PubMed

Ahn, H Y; Kim, M; Ahn, Y-T; Sim, J-H; Choi, I-D; Lee, S-H; Lee, J H

2015-08-01

This study evaluated the triglyceride (TG)-lowering effects of consuming dual probiotic strains of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on the fasting plasma metabolome. A randomized, double-blind, placebo-controlled study was conducted on 92 participants with hypertriglyceridemia but without diabetes. Over a 12-week testing period, the probiotic group consumed 2 g of powder containing 5 × 10(9) colony-forming units (cfu) of L. curvatus HY7601 and 5 × 10(9) cfu of L. plantarum KY1032 each day, whereas the placebo group consumed the same product without probiotics. Fasting plasma metabolomes were profiled using UPLC-LTQ-Orbitrap MS. After 12 weeks of treatment, the probiotic group displayed a 20% reduction (p = 0.001) in serum TGs and 25% increases (p=0.001) in apolipoprotein A-V (apoA-V). At the 12-week follow-up assessment, the following 11 plasma metabolites were significantly reduced in the probiotic group than the placebo group: palmitoleamide, palmitic amide, oleamide, and lysophosphatidyl choline (lysoPC) containing C14:0, C16:1, C16:0, C17:0, C18:3, C18:2, C18:1, and C20:3. In the probiotic group, changes (▵) in TG were negatively correlated with ▵ apoA-V, which was positively correlated with ▵ FFA. In addition, ▵ FFA was strongly and positively correlated with ▵ lysoPCs in the probiotic group but not the placebo group. The triglyceride-lowering effects of probiotic supplementation, partly through elevated apoA-V, in borderline to moderate hypertriglyceridemic subjects showed reductions in plasma metabolites, fatty acid primary amides and lysoPCs (NCT02215694; http://www.clinicaltrials.gov). Clinical trials: NCT02215694; http://www.clinicaltrials.gov. Copyright © 2015 Elsevier B.V. All rights reserved.

Urban FFA Members' Sense of the Organizational Culture of the FFA

ERIC Educational Resources Information Center

Martin, Michael J.; Kitchel, Tracy

2014-01-01

Organizational culture shapes how members of a group act. The culture has the power to exclude potential new members who do not fit into the culture of the organization. Research on urban school-based agriculture programs has indicated that urban agriculture students face barriers to their participation in the National FFA Organization (FFA).…

Student Self-Perceptions of Leadership in Two Missouri FFA Chapters: A Collective Case Study

ERIC Educational Resources Information Center

Kagay, Rachel Bartholomew; Marx, Adam A.; Simonsen, Jon C.

2015-01-01

The focus of this study is the self-perceptions of leadership engagement of FFA members in two FFA chapters in Missouri. This multiple case study used documentation of student self-perceptions, researcher observations, and focus groups. The two cases included 24 high school students comprised of FFA officers and members, who provided their…

Lipid and other plasma markers are associated with anxiety, depression, and fatigue.

PubMed

Lieberman, Harris R; Kellogg, Mark D; Kramer, F Matthew; Bathalon, Gaston P; Lesher, Larry L

2012-03-01

Few peripheral metabolites have been shown to be associated with mood in healthy individuals or patients with central nervous system diseases. During military basic combat training (BCT), mood state, physical performance and body composition substantially improve, providing an opportunity to examine relationships between mood and nutritional and hormonal biomarkers. Thirty-five females enrolled in U.S. Marine BCT, an intense physically and mentally challenging 12-week course, were studied. Every 4 weeks, mood was assessed with the Profile of Mood States (POMS), as were nutritional, metabolic and hormonal plasma markers. Mood and fitness improved over BCT, and there were substantial changes in biochemical markers. Multiple regression demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine, triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S), ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion, 37% fatigue, 27% depression and 40% in total mood (p < .0001). Increased HDL, FFA, DHEA-S, and substance P were associated with degraded mood (p < .05). Increased LDL, triglycerides, fructosamine, and ACTH were associated with improved mood (p < .05). Other markers, including glucose, cortisol, and C-reactive protein were not associated with mood. Normal human mood state was associated with 8 plasma markers. Increased HDL and lower LDL, which are associated with improved cardiovascular status, were associated with negative affect. Fructosamine and substance P, not previously known to be related to mood, were associated with it. We are not aware of any biological parameters that in aggregate predict such a substantial proportion of variation in normal mood.

Studies concerning chronic and acute effects of L-carnitina in elite athletes.

PubMed

Drăgan, I G; Vasiliu, A; Georgescu, E; Eremia, N

1989-01-01

Chronic and acute effects of L-Carnitina (vials of 1 g L-Carnitina endovenous; per orally administered vials of 1 g L-Carnitina; tablets of 1 g L-Carnitina) were recorded in 110 top athletes (rowing, kayak-canoe, swimming, weightlifting medium and long-distance runners), 47 girls and 63 boys, by six double blind placebo trials and cross over. Significant changes were registered after L-Carnitina treatment (both for a single dose or after 3 weeks of treatment) compared to placebo, for FFA, triglycenides, lactic acid after exercise, evoked muscular potential, plasma carnitine (free and acetyl-carnitine), urine carnitine (free carnitine) and others. The authors explain these changes by the increase of free carnitine, which permits a larger quantity of FFA to enter the mitochondria and to be more extensively used as energy source in endurance and strength efforts. Based on these results the authors recommend L-Carnitina as an ergogenic aid in elite athletes, especially in endurance and strength sports.

Plasma fatty acyl-carnitines during 8 weeks of overfeeding: relation to diet energy expenditure and body composition: the PROOF study.

PubMed

Bray, George A; Redman, Leanne M; de Jonge, Lilian; Rood, Jennifer; Sutton, Elizabeth F; Smith, Steven R

2018-06-01

Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed patterns of fatty acyl carnitines. Copyright © 2018 Elsevier Inc. All rights reserved.

Robust expertise effects in right FFA

PubMed Central

McGugin, Rankin Williams; Newton, Allen T; Gore, John C; Gauthier, Isabel

2015-01-01

The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7Telsa, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2 respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas. PMID:25192631

Detection of Myopic Choroidal Neovascularization Using Optical Coherence Tomography Angiography.

PubMed

Miyata, Manabu; Ooto, Sotaro; Hata, Masayuki; Yamashiro, Kenji; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Nakanishi, Hideo; Ueda-Arakawa, Naoko; Takahashi, Ayako; Kuroda, Yoshimasa; Wakazono, Tomotaka; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

2016-05-01

To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV). Validity and reliability analysis. Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined. OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P < .001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively. Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Lipid digestibility and energy content of distillers corn oil in swine and poultry

USDA-ARS?s Scientific Manuscript database

Two experiments were conducted to determine the DE and ME, and apparent total tract digestibility of ether extract of 3 distillers corn oil (DCO; 4.9, 12.8, or 13.9% FFA), compared with a sample of refined corn oil (CO, 0.04% FFA), and an industrially-hydrolyzed high FFA DCO (93.8% FFA) in young pig...

The Impact of Learning Styles on Learning Outcomes at FFA Camp: What Campers Retain over Time

ERIC Educational Resources Information Center

Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

2013-01-01

Twenty-four states host FFA summer camps to support adolescent maturation along with indoctrination into the culture and values of the FFA. Camps typically include a variety of activities designed to engage members in social activities and non-formal academic content. More than 1500 campers attend the Oklahoma FFA Alumni Leadership Camp annually…

Many faces of expertise: fusiform face area in chess experts and novices.

PubMed

Bilalić, Merim; Langner, Robert; Ulrich, Rolf; Grodd, Wolfgang

2011-07-13

The fusiform face area (FFA) is involved in face perception to such an extent that some claim it is a brain module for faces exclusively. The other possibility is that FFA is modulated by experience in individuation in any visual domain, not only faces. Here we test this latter FFA expertise hypothesis using the game of chess as a domain of investigation. We exploited the characteristic of chess, which features multiple objects forming meaningful spatial relations. In three experiments, we show that FFA activity is related to stimulus properties and not to chess skill directly. In all chess and non-chess tasks, experts' FFA was more activated than that of novices' only when they dealt with naturalistic full-board chess positions. When common spatial relationships formed by chess objects in chess positions were randomly disturbed, FFA was again differentially active only in experts, regardless of the actual task. Our experiments show that FFA contributes to the holistic processing of domain-specific multipart stimuli in chess experts. This suggests that FFA may not only mediate human expertise in face recognition but, supporting the expertise hypothesis, may mediate the automatic holistic processing of any highly familiar multipart visual input.

Hormone, metabolic peptide, and nutrient levels in the earliest phases of rheumatoid arthritis-contribution of free fatty acids to an increased cardiovascular risk during very early disease.

PubMed

Tang, Man Wai; Koopman, Frieda A; Visscher, Jan P M; de Hair, Maria J; Gerlag, Danielle M; Tak, Paul Peter

2017-02-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with changes in several hormones and metabolic peptides. Crosstalk between these factors and the immune system may be important for homeostasis during inflammation. Here, we studied the levels of hormones, metabolic peptides, and nutrients in individuals at risk for developing RA (at risk). In total, 18 hormones, metabolic peptides, and nutrients were measured in fasting serum samples from 45 autoantibody-positive individuals at risk, 22 RA patients, and 16 healthy subjects. Triglyceride (TG) levels were also measured in an independent validation cohort of 32 individuals at risk, 20 early arthritis patients, and 20 healthy controls. We found an elevated TG level in individuals at risk and significantly higher TG levels in RA patients compared to healthy controls. These results were confirmed in the validation cohort. Similarly, free fatty acid (FFA) levels showed an increase in individuals at risk and were significantly higher in RA patients compared to healthy controls. In RA patients, FFA levels were positively correlated with disease activity. Pancreatic polypeptide (PP) and norepinephrine levels were highly significantly increased in individuals at risk and RA patients compared to healthy controls. TG and FFA levels are increased in RA patients and positively correlated with disease activity parameters. The results presented here suggest a role for FFAs in the pathogenesis of RA. Furthermore, PP and norepinephrine may be a biomarker that could assist in the identification of individuals at risk.

Nonsteroidal anti-inflammatory drug flufenamic acid is a potent activator of AMP-activated protein kinase.

PubMed

Chi, Yuan; Li, Kai; Yan, Qiaojing; Koizumi, Schuichi; Shi, Liye; Takahashi, Shuhei; Zhu, Ying; Matsue, Hiroyuki; Takeda, Masayuki; Kitamura, Masanori; Yao, Jian

2011-10-01

Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPKα phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca(2+) chelator) or depletion of extracellular Ca(2+), whereas it was mimicked by stimulation of cells with the Ca(2+) ionophore 5-(methylamino)-2-({(2R,3R,6S,8S,9R,11R)-3,9,11-trimethyl-8-[(1S)-1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl}methyl)-1,3-benzoxazole-4-carboxylic acid (A23187) or ionomycin. 3) FFA triggered a rise in intracellular Ca(2+), which was abolished by cyclosporine, a blocker of mitochondrial permeability transition pore. Cyclosporine also abolished FFA-induced activation of AMPK. 4) Inhibition of Ca(2+)/calmodulin-dependent kinase kinase β (CaMKKβ) with 7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609) or down-regulation of CaMKKβ with short interfering RNA largely abrogated FFA-induced activation of AMPK. 5) FFA significantly suppressed nuclear factor-κB activity and inducible nitric-oxide synthase expression triggered by interleukin-1β and tumor necrosis factor α. This suppression was also largely abrogated by STO-609. Taken together, we conclude that FFA induces AMPK activation through the Ca(2+)-CaMKKβ pathway. Activation of AMPK is a presently unrecognized important mechanism underlying the pharmacological effects of FFA.

Regional Neural Response Differences in the Determination of Faces or Houses Positioned in a Wide Visual Field

PubMed Central

Wu, Jinglong; Chen, Kewei; Imajyo, Satoshi; Ohno, Seiichiro; Kanazawa, Susumu

2013-01-01

In human visual cortex, the primary visual cortex (V1) is considered to be essential for visual information processing; the fusiform face area (FFA) and parahippocampal place area (PPA) are considered as face-selective region and places-selective region, respectively. Recently, a functional magnetic resonance imaging (fMRI) study showed that the neural activity ratios between V1 and FFA were constant as eccentricities increasing in central visual field. However, in wide visual field, the neural activity relationships between V1 and FFA or V1 and PPA are still unclear. In this work, using fMRI and wide-view present system, we tried to address this issue by measuring neural activities in V1, FFA and PPA for the images of faces and houses aligning in 4 eccentricities and 4 meridians. Then, we further calculated ratio relative to V1 (RRV1) as comparing the neural responses amplitudes in FFA or PPA with those in V1. We found V1, FFA, and PPA showed significant different neural activities to faces and houses in 3 dimensions of eccentricity, meridian, and region. Most importantly, the RRV1s in FFA and PPA also exhibited significant differences in 3 dimensions. In the dimension of eccentricity, both FFA and PPA showed smaller RRV1s at central position than those at peripheral positions. In meridian dimension, both FFA and PPA showed larger RRV1s at upper vertical positions than those at lower vertical positions. In the dimension of region, FFA had larger RRV1s than PPA. We proposed that these differential RRV1s indicated FFA and PPA might have different processing strategies for encoding the wide field visual information from V1. These different processing strategies might depend on the retinal position at which faces or houses are typically observed in daily life. We posited a role of experience in shaping the information processing strategies in the ventral visual cortex. PMID:23991147

SITES OF LIPOPROTEIN LIPASE ACTIVITY IN ADIPOSE TISSUE PERFUSED WITH CHYLOMICRONS

PubMed Central

Blanchette-Mackie, E. Joan; Scow, Robert O.

1971-01-01

Lipoprotein lipase activity was studied in rat parametrial adipose tissue perfused with chylomicrons and in gelatin blocks containing postheparin plasma and chylomicrons. The tissues and blocks were fixed in glutaraldehyde and incubated in 0.035 M CaCl2-0.1 M Tris medium (pH 8.3) at 38°C. The doubly labeled chylomicron triglycerides (glycerol-3H and palmitate-14C) in the tissues and blocks were hydrolyzed during incubation to free fatty acids (FFA) and the FFA remained in the specimens; hydrolysis was inhibited by 0.004 M diethyl paranitrophenyl phosphate (E-600). Incubated blocks and tissue were treated with 0.05 M Pb(NO3)2, postfixed in OsO4, dehydrated with acetone, embedded in Epon, and examined by electron microscopy. The incubated blocks contained electronlucent areas and granular and laminar precipitates at sites of hydrolysis. Similar precipitates were found in incubated tissue, within vacuoles and microvesicles of capillary endothelium, and in the subendothelial space (between the endothelium and pericytes), but not in the capillary lumen or in or near fat cells. The cytochemical reaction was greatly reduced, in blocks and tissues incubated with E-600. It is concluded that plasma glycerides are hydrolyzed by lipoprotein lipase in capillary endothelial cells and in the subendothelial space of adipose tissue and that glycerides across the endothelial cells within a membrane-bounded system. PMID:4329521

Short-chain fatty acid sensing in rat duodenum

PubMed Central

Akiba, Yasutada; Inoue, Takuya; Kaji, Izumi; Higashiyama, Masaaki; Narimatsu, Kazuyuki; Iwamoto, Ken-ichi; Watanabe, Masahiko; Guth, Paul H; Engel, Eli; Kuwahara, Atsukazu; Kaunitz, Jonathan D

2015-01-01

Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3− secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3− exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3− exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia. PMID:25433076

Impact of different wort boiling temperatures on the beer foam stabilizing properties of lipid transfer protein 1.

PubMed

Van Nierop, Sandra N E; Evans, David E; Axcell, Barry C; Cantrell, Ian C; Rautenbach, Marina

2004-05-19

Beer consumers demand satisfactory and consistent foam stability; thus, it is a high priority for brewers. Beer foam is stabilized by the interaction between certain beer proteins, including lipid transfer protein 1 (LTP1), and isomerized hop alpha-acids, but destabilized by lipids. In this study it was shown that the wort boiling temperature during the brewing process was critical in determining the final beer LTP1 content and conformation. LTP1 levels during brewing were measured by an LTP1 ELISA, using antinative barley LTP1 polyclonal antibodies. It was observed that the higher wort boiling temperatures ( approximately 102 degrees C), resulting from low altitude at sea level, reduced the final beer LTP1 level to 2-3 microg/mL, whereas the lower wort boiling temperatures ( approximately 96 degrees C), resulting from higher altitudes (1800 m), produced LTP1 levels between 17 and 35 microg/mL. Low levels of LTP1 in combination with elevated levels of free fatty acids (FFA) resulted in poor foam stability, whereas beer produced with low levels of LTP1 and FFA had satisfactory foam stability. Previous studies indicated the need for LTP1 denaturing to improve its foam stabilizing properties. However, the results presented here show that LTP1 denaturation reduces its ability to act as a binding protein for foam-damaging FFA. These investigations suggest that wort boiling temperature is an important factor in determining the level and conformation of LTP1, thereby favoring satisfactory beer foam stability.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.

Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To testmore » this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.« less

Development of prediction equations to estimate the apparent digestible energy content of lipids when fed to lactating sows.

PubMed

Rosero, D S; Odle, J; Arellano, C; Boyd, R D; van Heugten, E

2015-03-01

Two studies were conducted 1) to determine the effects of free fatty acid (FFA) concentrations and the degree of saturation of lipids (unsaturated to saturated fatty acids ratio [U:S]) on apparent total tract digestibility (ATTD) and DE content of lipids and 2) to derive prediction equations to estimate the DE content of lipids when added to lactating sow diets. In Exp. 1, 85 lactating sows were assigned randomly to a 4 × 5 factorial arrangement of treatments plus a control diet with no added lipid. Factors included 1) FFA concentrations of 0, 18, 36, and 54% and 2) U:S of 2.0, 2.8, 3.5, 4.2, and 4.9. Diets were corn-soybean meal based and lipid was supplemented at 6%. Concentrations of FFA and U:S were obtained by blending 4 lipid sources: choice white grease (CWG; FFA = 0.3% and U:S = 2.0), soybean oil (FFA = 0.1% and U:S = 5.5), CWG acid oil (FFA = 57.8% and U:S = 2.1), and soybean-cottonseed acid oil (FFA = 67.5% and U:S = 3.8). Titanium dioxide was added to diets (0.5%) as a digestibility marker. Treatments started on d 4 of lactation and fecal samples were collected after 6 d of adaptation to diets on a daily basis from d 10 to 13. The ATTD of added lipid and DE content of lipids were negatively affected (linear, < 0.001) with increasing FFA concentrations, but negative effects were less pronounced with increasing U:S (interaction, < 0.05). Coefficients of ATTD for the added lipid and DE content of lipids increased with increasing U:S (quadratic, = 0.001), but these improvements were less pronounced when the FFA concentration was less than 36%. Digestible energy content of added lipid was described by DE (kcal/kg) = [8,381 - (80.6 × FFA) + (0.4 × FFA) + (248.8 × U:S) - (28.1 × U:S) + (12.8 × FFA × U:S)] ( = 0.74). This prediction equation was validated in Exp. 2, in which 24 lactating sows were fed diets supplemented with 6% of either an animal-vegetable blend (A-V; FFA = 14.5% and U:S = 2.3) or CWG (FFA = 3.7% and U:S = 1.5) plus a control diet with no added lipids. Digestible energy content of A-V (8,317 and 8,127 kcal/kg for measured and predicted values, respectively) and CWG (8,452 and 8,468 kcal/kg for measured and predicted values, respectively) were accurately estimated using the proposed equation. The proposed equation involving FFA concentration and U:S resulted in highly accurate estimations of DE content (relative error, +0.2 to -2.3%) of commercial sources of lipids for lactating sows.

Is this car looking at you? How anthropomorphism predicts fusiform face area activation when seeing cars.

PubMed

Kühn, Simone; Brick, Timothy R; Müller, Barbara C N; Gallinat, Jürgen

2014-01-01

Anthropomorphism encompasses the attribution of human characteristics to non-living objects. In particular the human tendency to see faces in cars has long been noticed, yet its neural correlates are unknown. We set out to investigate whether the fusiform face area (FFA) is associated with seeing human features in car fronts, or whether, the higher-level theory of mind network (ToM), namely temporoparietal junction (TPJ) and medial prefrontal cortex (MPFC) show a link to anthropomorphism. Twenty participants underwent fMRI scanning during a passive car-front viewing task. We extracted brain activity from FFA, TPJ and MPFC. After the fMRI session participants were asked to spontaneously list adjectives that characterize each car front. Five raters judged the degree to which each adjective can be applied as a characteristic of human beings. By means of linear mixed models we found that the implicit tendency to anthropomorphize individual car fronts predicts FFA, but not TPJ or MPFC activity. The results point to an important role of FFA in the phenomenon of ascribing human attributes to non-living objects. Interestingly, brain regions that have been associated with thinking about beliefs and mental states of others (TPJ, MPFC) do not seem to be related to anthropomorphism of car fronts.

Investigating the relationship between internal tibial torsion and medial collateral ligament injury in patients undergoing knee arthroscopy due to tears in the posterior one third of the medial meniscus.

PubMed

Guler, Olcay; Isyar, Mehmet; Karataş, Dilek; Ormeci, Tugrul; Cerci, Halis; Mahirogulları, Mahir

2016-08-01

To evaluate the relationship between medial collateral ligament (MCL) injury and degree of internal tibial torsion in patients who had undergone arthroscopic resection due to tears in the posterior one third of the medial meniscus. Seventy-one patients were allocated into two groups with respect to foot femur angle (FFA) and transmalleolar angle (TMA) (Group 1 31 patients with FFA<8° and Group 2 40 patients with FFA≥8°). The groups were compared in terms of valgus instability, Lysholm score, magnetic resonance view, FFA, and TMA, both before and after the operation. Lysholm scores were higher in Group 2 at both postoperative week 1 (p<0.001) and month 1 (p=0.045) relative to Group 1. Preoperative cartilage injury was encountered more frequently in Group 1 (p=0.037) than in Group 2. MCL injury was detected more frequently in Group 1 compared to Group 2 postoperatively at week 1 (p=0.001). We conclude that FFA and TFA, indicators of internal tibial torsion, may serve as markers for foreseeing clinical improvement and complications following arthroscopic surgery. level III retrospective comparative study. Copyright © 2015 Elsevier B.V. All rights reserved.

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

PubMed

Singh, Lakshman; Tyagi, Sonia; Myers, Damian; Duque, Gustavo

2018-04-01

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

Functional dissociation of the left and right fusiform gyrus in self-face recognition.

PubMed

Ma, Yina; Han, Shihui

2012-10-01

It is well known that the fusiform gyrus is engaged in face perception, such as the processes of face familiarity and identity. However, the functional role of the fusiform gyrus in face processing related to high-level social cognition remains unclear. The current study assessed the functional role of individually defined fusiform face area (FFA) in the processing of self-face physical properties and self-face identity. We used functional magnetic resonance imaging to monitor neural responses to rapidly presented face stimuli drawn from morph continua between self-face (Morph 100%) and a gender-matched friend's face (Morph 0%) in a face recognition task. Contrasting Morph 100% versus Morph 60% that differed in self-face physical properties but were both recognized as the self uncovered neural activity sensitive to self-face physical properties in the left FFA. Contrasting Morphs 50% that were recognized as the self versus a friend on different trials revealed neural modulations associated with self-face identity in the right FFA. Moreover, the right FFA activity correlated with the frequency of recognizing Morphs 50% as the self. Our results provide evidence for functional dissociations of the left and right FFAs in the representations of self-face physical properties and self-face identity. Copyright © 2011 Wiley Periodicals, Inc.

Is This Car Looking at You? How Anthropomorphism Predicts Fusiform Face Area Activation when Seeing Cars

PubMed Central

Kühn, Simone; Brick, Timothy R.; Müller, Barbara C. N.; Gallinat, Jürgen

2014-01-01

Anthropomorphism encompasses the attribution of human characteristics to non-living objects. In particular the human tendency to see faces in cars has long been noticed, yet its neural correlates are unknown. We set out to investigate whether the fusiform face area (FFA) is associated with seeing human features in car fronts, or whether, the higher-level theory of mind network (ToM), namely temporoparietal junction (TPJ) and medial prefrontal cortex (MPFC) show a link to anthropomorphism. Twenty participants underwent fMRI scanning during a passive car-front viewing task. We extracted brain activity from FFA, TPJ and MPFC. After the fMRI session participants were asked to spontaneously list adjectives that characterize each car front. Five raters judged the degree to which each adjective can be applied as a characteristic of human beings. By means of linear mixed models we found that the implicit tendency to anthropomorphize individual car fronts predicts FFA, but not TPJ or MPFC activity. The results point to an important role of FFA in the phenomenon of ascribing human attributes to non-living objects. Interestingly, brain regions that have been associated with thinking about beliefs and mental states of others (TPJ, MPFC) do not seem to be related to anthropomorphism of car fronts. PMID:25517511

The fusiform face area: a cortical region specialized for the perception of faces

PubMed Central

Kanwisher, Nancy; Yovel, Galit

2006-01-01

Faces are among the most important visual stimuli we perceive, informing us not only about a person's identity, but also about their mood, sex, age and direction of gaze. The ability to extract this information within a fraction of a second of viewing a face is important for normal social interactions and has probably played a critical role in the survival of our primate ancestors. Considerable evidence from behavioural, neuropsychological and neurophysiological investigations supports the hypothesis that humans have specialized cognitive and neural mechanisms dedicated to the perception of faces (the face-specificity hypothesis). Here, we review the literature on a region of the human brain that appears to play a key role in face perception, known as the fusiform face area (FFA). Section 1 outlines the theoretical background for much of this work. The face-specificity hypothesis falls squarely on one side of a longstanding debate in the fields of cognitive science and cognitive neuroscience concerning the extent to which the mind/brain is composed of: (i) special-purpose (‘domain-specific’) mechanisms, each dedicated to processing a specific kind of information (e.g. faces, according to the face-specificity hypothesis), versus (ii) general-purpose (‘domain-general’) mechanisms, each capable of operating on any kind of information. Face perception has long served both as one of the prime candidates of a domain-specific process and as a key target for attack by proponents of domain-general theories of brain and mind. Section 2 briefly reviews the prior literature on face perception from behaviour and neurophysiology. This work supports the face-specificity hypothesis and argues against its domain-general alternatives (the individuation hypothesis, the expertise hypothesis and others). Section 3 outlines the more recent evidence on this debate from brain imaging, focusing particularly on the FFA. We review the evidence that the FFA is selectively engaged in face perception, by addressing (and rebutting) five of the most widely discussed alternatives to this hypothesis. In §4, we consider recent findings that are beginning to provide clues into the computations conducted in the FFA and the nature of the representations the FFA extracts from faces. We argue that the FFA is engaged both in detecting faces and in extracting the necessary perceptual information to recognize them, and that the properties of the FFA mirror previously identified behavioural signatures of face-specific processing (e.g. the face-inversion effect). Section 5 asks how the computations and representations in the FFA differ from those occurring in other nearby regions of cortex that respond strongly to faces and objects. The evidence indicates clear functional dissociations between these regions, demonstrating that the FFA shows not only functional specificity but also area specificity. We end by speculating in §6 on some of the broader questions raised by current research on the FFA, including the developmental origins of this region and the question of whether faces are unique versus whether similarly specialized mechanisms also exist for other domains of high-level perception and cognition. PMID:17118927

Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells.

PubMed

Pongkorpsakol, Pawin; Yimnual, Chantapol; Chatsudthipong, Varanuj; Rukachaisirikul, Vatcharin; Muanprasat, Chatchai

2017-06-01

Intestinal Cl - secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA) suppressed Vibrio cholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl - secretion in human intestinal epithelial (T84) cells. FFA inhibited cAMP-dependent Cl - secretion in T84 cell monolayers with IC 50 of ∼8 μM. Other fenamate drugs including tolfenamic acid, meclofenamic acid and mefenamic acid exhibited the same effect albeit with lower potency. FFA also inhibited activities of CFTR, a cAMP-activated apical Cl - channel, and KCNQ1/KCNE3, a cAMP-activated basolateral K + channel. Mechanisms of CFTR inhibition by FFA did not involve activation of its negative regulators. Interestingly, FFA inhibited Ca 2+ -dependent Cl - secretion with IC 50 of ∼10 μM. FFA inhibited activities of Ca 2+ -activated Cl - channels and K Ca 3.1, a Ca 2+ -activated basolateral K + channels, but had no effect on activities of Na + -K + -Cl - cotransporters and Na + -K + ATPases. These results indicate that FFA inhibits both cAMP and Ca 2+ -dependent Cl - secretion by suppressing activities of both apical Cl - channels and basolateral K + channels. FFA and other fenamate drugs may be useful in the treatment of secretory diarrheas. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease.

PubMed

Madsen, Trine; Christensen, Jeppe Hagstrup; Toft, Egon; Aardestrup, Inge; Lundbye-Christensen, Søren; Schmidt, Erik B

2011-01-01

Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω-3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω-3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. Forty-four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω-3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. The increase in ω-3 FFAs was greater in the ω-3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω-3 PUFA group, ω-3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω-3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω-3 PUFAs in plasma and platelet phospholipids. Intravenous ω-3 PUFAs administered during HD caused a transient selective increase in ω-3 FFA concentration. Furthermore, ω-3 PUFAs were rapidly incorporated into platelets, and the content of ω-3 PUFAs in plasma phospholipids increased after 48 hours.

Association of consumption of fried food away from home with body mass index and diet quality in older children and adolescents.

PubMed

Taveras, Elsie M; Berkey, Catherine S; Rifas-Shiman, Sheryl L; Ludwig, David S; Rockett, Helaine R H; Field, Alison E; Colditz, Graham A; Gillman, Matthew W

2005-10-01

Rates of overweight have increased dramatically among children in the United States. Although an increase in consumption of food prepared away from home has paralleled overweight trends, few data exist relating food prepared away from home to change in BMI in children. The goals of this study were to (1) examine the cross-sectional and longitudinal associations between consumption of fried foods away from home (FFA) and BMI and (2) examine the cross-sectional associations between intake of FFA and several measures of diet quality. We studied a cohort of 7745 girls and 6610 boys, aged 9 to 14 years, at baseline in 1996. We obtained BMI from self-reported height and weight, measures of diet quality from a food frequency questionnaire, and weekly servings of FFA during the previous year. We performed linear regression analyses to assess the longitudinal associations between change in consumption of FFA on change in BMI, using data from three 1-year periods from 1996 through 1999. We also related consumption of FFA with intake of selected foods and nutrients at baseline. In cross-sectional analyses, adjusting for potential confounders, mean (SE) BMI was 19.1 (0.13) among children who ate FFA "never or <1/week," 19.2 (0.13) among those who responded "1 to 3 times/week," and 19.3 (0.18) among those who responded "4 to 7 times/week." In longitudinal multivariate models, increasing (over 1 year) consumption of FFA "never or <1/week" to "4 to 7/week" was associated with increasing BMI (beta = 0.21 kg/m2; 95% confidence interval: 0.03-0.39) compared with those with low consumption of FFA at baseline and 1 year later. At baseline, frequency of eating FFA was associated with greater intakes of total energy, sugar-sweetened beverages, and trans fat, as well as lower consumption of low-fat dairy foods and fruits and vegetables. These data suggest that older children who consume greater quantities of FFA are heavier, have greater total energy intakes, and have poorer diet quality. Furthermore, increasing consumption of FFA over time may lead to excess weight gain.

Oleic acid exposure of cultured endothelial cells alters lipid mediator production

EPA Science Inventory

Diesel, biodiesel, and other combustion sources contain free fatty acid (FFA) components capable of entering the body through particulate inhalation. FFA can also be endogenously released into circulation in response to stress. When in circulation, bioactive FFA may interact with...

Pleiotropic Effects of Chronic Phorbol Ester Treatment to Improve Glucose Transport in Insulin-Resistant Cardiomyocytes.

PubMed

Viglino, Christelle; Khoramdin, Bahareh; Praplan, Guillaume; Montessuit, Christophe

2017-12-01

Stimulation of glucose transport is an important determinant of myocardial susceptibility to ischemia and reperfusion. Stimulation of glucose transport is markedly impaired in cardiomyocytes exposed to free fatty acids (FFA). Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose transport impairment, and could be corrected by chronic treatment with the phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation to restore stimulated glucose transport. Chronic treatment with TPA improved basal and stimulated glucose transport in FFA-exposed, but not in control cardiomyocytes. Chronic FFA exposure induced the activation of PKCδ and PKCϵ. TPA markedly downregulated the expression of PKCα, PKCδ, and PKCϵ, suggesting that PKCδ or PKCϵ activation could contribute to inhibition of glucose transport by FFA. Rottlerin, a specific PKCδ inhibitor, improved glucose transport in FFA-exposed cardiomyocytes; and PKCδ was reduced in the particulate fraction of FFA + TPA-exposed cardiomyocytes. TPA also activated Protein Kinase D 1(PKD1) in FFA-exposed cardiomyocytes, as assessed by autophosphorylation of PKD1 on Y916. Pharmaceutical inhibition of PKD1 only partially prevented the improvement of glucose transport by TPA. Chronic TPA treatment also increased basal and stimulated glycolysis and favored accumulation of lipid droplets in FFA-exposed cardiomyocytes. In conclusion, basal and stimulated glucose transport in cardiomyocytes is reduced by chronic FFA exposure, but restored by concomitant treatment with a phorbol ester. The mechanism of action of phorbol esters may involve downregulation of PKCδ, activation of PKD1 and a general switch from fatty acid to glucose metabolism. J. Cell. Biochem. 9999: 4716-4727, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway.

PubMed

Foo, Joo-Pin; Aronis, Konstantinos N; Chamberland, John P; Paruthi, Jason; Moon, Hyun-Seuk; Mantzoros, Christos S

2013-04-01

Fibroblast growth factor (FGF)-21 is an endocrine factor with potent metabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated. We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assess whether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 a.m. on day 4 until 8:00 a.m. on day 5. FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close cross-correlations with FFA in both fed state and energy deprivation, needs to be studied further.

A novel bioactive derivative of eicosapentaenoic acid (EPA) suppresses intestinal tumor development in ApcΔ14/+ mice.

PubMed

Nakanishi, Masako; Hanley, Matthew P; Zha, Ruochen; Igarashi, Yuichi; Hull, Mark A; Mathias, Gary; Sciavolino, Frank; Grady, James J; Rosenberg, Daniel W

2018-03-08

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.

The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.

PubMed

Kadiri, Sarah; Monnier, Chloé; Ganbold, Munkhzul; Ledent, Tatiana; Capeau, Jacqueline; Antoine, Bénédicte

2015-07-15

Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by lipolysis to reesterification into triglycerides, thus regulating FFA homeostasis and fat mass. Glyceroneogenesis shares with hepatic gluconeogenesis the key enzyme phosphoenolpyruvate carboxykinase c (PEPCKc), whose gene is a RORα target in the liver. RORα-deficient mice (staggerer, ROR(sg/sg)) have been shown to exhibit a lean phenotype and fasting hypoglycemia for unsolved reasons. In the present study, we investigated whether adipocyte glyceroneogenesis might also be a target pathway of RORα, and we further evaluated the role of RORα in hepatocyte gluconeogenesis. In vivo investigations comparing ROR(sg/sg) mice with their wild-type (WT) littermates under fasting conditions demonstrated that, in the absence of RORα, the release of FFA into the bloodstream was altered and the rise in glycemia in response to pyruvate reduced. The functional analysis of each pathway, performed in adipose tissue or liver explants, confirmed the impairment of adipocyte glyceroneogenesis and liver gluconeogenesis in the ROR(sg/sg) mice; these reductions of FFA reesterification or glucose production were associated with decreases in PEPCKc mRNA and protein levels. Treatment of explants with RORα agonist or antagonist enhanced or inhibited these pathways, respectively, in tissues isolated from WT but not ROR(sg/sg) mice. Our results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα. This study demonstrates the physiological function of RORα in regulating both glucose and FFA homeostasis. Copyright © 2015 the American Physiological Society.

Degree of free fatty acid saturation influences chocolate rejection in human assessors.

PubMed

Running, Cordelia A; Hayes, John E; Ziegler, Gregory R

2017-02-01

In foods, free fatty acids (FFAs) traditionally have been viewed as contributing an odor, yet evidence has accumulated that FFAs also contribute a unique taste ("oleogustus"). However, minimal work has been conducted using actual foods to test the contribution of FFA to taste preferences. Here, we investigate flavor, taste, and aroma contributions of added FFA in chocolate, as some commercial manufacturers already use lipolysis of triglycerides to generate unique profiles. We hypothesized that small added concentrations of FFAs would increase preferences for chocolate, whereas higher added concentrations would decrease preferences. We also hypothesized a saturated fatty acid (stearic C18) would have a lesser effect than a monounsaturated (oleic C18:1), which would have a lesser effect than a polyunsaturated (linoleic C18:2) fatty acid. For each, paired preference tests were conducted for 10 concentrations (0.04% to 2.25%) of added FFAs compared with the control chocolate without added FFAs. Stearic acid was tested for flavor (tasting and nares open), whereas the unsaturated fatty acids were tested for both aroma (orthonasal only and no tasting) and taste (tasting with nares blocked to eliminate retronasal odor). We found no preference for any added FFA chocolate; however, rejection was observed independently for both taste and aroma of unsaturated fatty acids, with linoleic acid reaching rejection at lower concentrations than oleic acid. These data indicate that degree of unsaturation influences rejection of both FFA aroma and taste in chocolate. Thus, alterations of FFA profiles in foods should be approached cautiously to avoid shifting concentrations of unsaturated fatty acids to hedonically unacceptable levels. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Being BOLD: The neural dynamics of face perception.

PubMed

Gentile, Francesco; Ales, Justin; Rossion, Bruno

2017-01-01

According to a non-hierarchical view of human cortical face processing, selective responses to faces may emerge in a higher-order area of the hierarchy, in the lateral part of the middle fusiform gyrus (fusiform face area [FFA]) independently from face-selective responses in the lateral inferior occipital gyrus (occipital face area [OFA]), a lower order area. Here we provide a stringent test of this hypothesis by gradually revealing segmented face stimuli throughout strict linear descrambling of phase information [Ales et al., 2012]. Using a short sampling rate (500 ms) of fMRI acquisition and single subject statistical analysis, we show a face-selective responses emerging earlier, that is, at a lower level of structural (i.e., phase) information, in the FFA compared with the OFA. In both regions, a face detection response emerging at a lower level of structural information for upright than inverted faces, both in the FFA and OFA, in line with behavioral responses and with previous findings of delayed responses to inverted faces with direct recordings of neural activity were also reported. Overall, these results support the non-hierarchical view of human cortical face processing and open new perspectives for time-resolved analysis at the single subject level of fMRI data obtained during continuously evolving visual stimulation. Hum Brain Mapp 38:120-139, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis.

PubMed

Sun, Xiaoyan; Wray, Curtis; Tian, Xintian; Hasselgren, Per-Olof; Lu, James

2003-09-01

Uncoupling protein 3 (UCP3) is a member of the mitochondrial transporter superfamily that is expressed primarily in skeletal muscle. UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and treatment with glucocorticoids (GCs). The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known. We examined UCP3 gene and protein expression in skeletal muscles from rats after cecal ligation and puncture and from sham-operated control rats. Sepsis resulted in a two- to threefold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased 2.4- to 3.6-fold when incubated muscles from normal rats were treated with dexamethasone (DEX) and/or free fatty acids (FFA) ex vivo. In addition, UCP3 mRNA and protein levels were significantly increased in normal rat muscles in vivo with treatment of either DEX or FFA. The results suggest that sepsis upregulates the gene and protein expression of UCP3 in skeletal muscle, which may at least in part be mediated by GCs and FFA.

Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects.

PubMed

Lee, Sang-Rok; Schriefer, Johnhenry M; Gunnels, Trint A; Harvey, Innocence C; Bloomer, Richard J

2013-10-21

Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6-8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.

Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects

PubMed Central

2013-01-01

Background Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist—possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Methods Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6–8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. Results A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. Conclusion Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women. PMID:24139127

Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

PubMed

Uchiyama, Masayuki; Oguri, Masashi; Mojumdar, Enamul H; Gooris, Gert S; Bouwstra, Joke A

2016-09-01

The lipid matrix in the stratum corneum (SC) plays an important role in the barrier function of the skin. The main lipid classes in this lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to determine whether a variation in CER subclass composition and chain length distribution of FFAs affect the permeability of this matrix. To examine this, we make use of lipid model membranes, referred to as stratum corneum substitute (SCS). We prepared SCS containing i) single CER subclass with either a single FFA or a mixture of FFAs and CHOL, or ii) a mixture of various CER subclasses with either a single FFA or a mixture of FFAs and CHOL. In vitro permeation studies were performed using ethyl-p-aminobenzoic acid (E-PABA) as a model drug. The flux of E-PABA across the SCS containing the mixture of FFAs was higher than that across the SCS containing a single FA with a chain length of 24 C atoms (FA C24), while the E-PABA flux was not effected by the CER composition. To select the underlying factors for the changes in permeability, the SCSs were examined by Fourier transform infrared spectroscopy (FTIR) and Small angle X-ray scattering (SAXS). All lipid models demonstrated a similar phase behavior. However, when focusing on the conformational ordering of the individual FFA chains, the shorter chain FFA (with a chain length of 16, 18 or 20 C atoms forming only 11m/m% of the total FFA level) had a higher conformational disordering, while the conformational ordering of the chains of the CER and FA C24 and FA C22 hardly did not change irrespective of the composition of the SCS. In conclusion, the conformational mobility of the short chain FFAs present only at low levels in the model SC lipid membranes has a great impact on the permeability of E-PABA. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Stigmasterol and β-Sitosterol on Nonalcoholic Fatty Liver Disease in a Mouse Model: A Lipidomic Analysis.

PubMed

Feng, Simin; Gan, Ling; Yang, Chung S; Liu, Anna B; Lu, Wenyun; Shao, Ping; Dai, Zhuqing; Sun, Peilong; Luo, Zisheng

2018-04-04

To study the effects of stigmasterol and β-sitosterol on high-fat Western diet (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were conducted in liver samples collected after 33 weeks of the treatment. Principal component analysis showed these phytosterols were effective in protecting against HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs), phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids (FFAs) were the major lipid species contributing to these discriminations. The alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol, TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In conclusion, phytosterols, at a dose comparable to that suggested for humans by the FDA for the reduction of plasma cholesterol levels, are shown to protect against NAFLD in this long-term (33-week) study.

Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic vs. normal glucose tolerant overweight and obese Latino adolescents

PubMed Central

Toledo-Corral, Claudia M.; Alderete, Tanya L.; Richey, Joyce; Sequeira, Paola; Goran, Michael I.; Weigensberg, Marc J.

2014-01-01

Background and Objective Type 2 diabetes risk and its relationship to free fatty acid (FFA) exposure and visceral fat by prediabetes status in minority adolescents has yet to be explored. Therefore, the objective of this study was to examine the association of circulating FFA under varying conditions with prediabetes in Latino adolescents and to determine the relative relationships of FFA and visceral adiposity to insulin sensitivity, secretion, and β-cell function. Subjects and Outcome Measures Overweight or obese, but otherwise healthy Latino adolescent males and females (n=164, 14.2±2.5 years) were recruited for assessment of prediabetes, abdominal fat, and FFA levels taken at a fasting state (FFAF), during an OGTT (FFAOGTT), and overnight (FFANOCTURNAL). Results Prediabetic adolescents had a higher FFAF than those with normal glucose tolerance when controlling for age, sex, pubertal status, total percent body fat, and visceral fat. FFAOGTT and FFANOCTURNAL did not differ between participants with prediabetes and those with normal glucose tolerance after adjusting for covariates. Visceral fat was independently related to insulin sensitivity and secretion in pubertal adolescents, however in post-pubertal adolescents, FFAF and visceral fat were both independent and negatively related to β-cell function. Conclusion These results support a plausible progression of the lipotoxicity theory of diabetes development during the pubertal transition. PMID:25109287

Associations Between Insulin Resistance, Free Fatty Acids, and Oocyte Quality in Polycystic Ovary Syndrome During In Vitro Fertilization

PubMed Central

Niu, Zhihong; Lin, Nan; Gu, Ruihuan; Sun, Yijuan

2014-01-01

Context: Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation Objective: Our objective was to determine the effect of FFA metabolism in plasma and follicular fluid on oocyte quality in the women with PCOS undergoing in vitro fertilization. Design and Setting: Ninety-three women undergoing in vitro fertilization treatment, including 55 with PCOS and 38 age-matched controls, were recruited. PCOS patients were divided into obese and nonobese subgroups on the basis of their body mass index. Main Outcome Measures: Embryo quality was morphologically assessed, and serum sex hormone and insulin levels were measured. FFAs in plasma and follicular fluid were measured using gas chromatography-mass spectrometry. Results: PCOS was found to be associated with significantly higher LH/FSH, total T, free androgen index (FAI), and lower SHBG levels, independent of obesity(P < .05). Obese women with PCOS had a significantly higher total T level, FAI, fasting insulin, insulin resistance index as determined by homeostasis model assessment for insulin resistance, and lower SHBG levels than the nonobese women with PCOS (P < .05). The embryo fragmentation score was significantly positively correlated with the oleic acid concentration in all PCOS patients (r = 0.22, P = .04, for nonobese patients and r = 0.25, P = .03, for obese patients). Conclusions: Our findings clearly demonstrated that PCOS is associated with significantly higher FAI and insulin resistance levels and decreased plasma SHBG levels, independent of body mass index. Obese PCOS patients had higher palmitoleic acid and oleic acid levels in both the plasma and follicular fluid than did the control subject and nonobese PCOS patients. Our results indicated that developmental competence is associated with oleic and stearic acid concentrations, which may contribute to the poor pregnancy outcomes in patients with PCOS. PMID:24694334

Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry.

PubMed

Zhao, Xinjie; Xu, Fang; Qi, Bing; Hao, Songli; Li, Yanjie; Li, Yan; Zou, Lihong; Lu, Caixia; Xu, Guowang; Hou, Lihui

2014-02-07

Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder, which produces in 5-10% reproductive age women. In this study, a nontargeted metabolomics approach based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is used to investigate serum metabolic characteristics of PCOS. PCOS women and healthy control can be clustered into two distinct groups based on multivariate statistical analysis. Significant increase in the levels of unsaturated free fatty acids, fatty acid amides, sulfated steroids, glycated amino acid and the decrease in levels of lysophosphatidylcholines, lysophosphatidylethanolamines, etc., were found. These metabolites showed abnormalities of lipid- and androgen-metabolism, increase of stearoyl-CoA desaturase (SCD) activity and accumulation of advanced glycation end-products in PCOS patients. On the basis of the binary logistic regression model, free fatty acid (FFA) 18:1/FFA 18:0, FFA 20:3, dihydrotestosterone sulfate, glycated phenylalanine, and uridine were combined as a diagnostic biomarker. The area under the curve (AUC) of combinational biomarker was 0.839 in 131 discovery phase samples and 0.874 in 109 validation phase samples. The findings of our study offer a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may provide a prospect for PCOS diagnosis.

Fundus fluorescence Angiography in diagnosing diabetic retinopathy.

PubMed

Wang, Shuhui; Zuo, Yuqin; Wang, Ning; Tong, Bin

2017-01-01

To investigate the manifestation characteristics of fundus fluorescence angiography (FFA) and its values in diagnosing diabetic retinopathy through comparing direct ophthalmoscopy. Two hundred fifty patients (500 eyes) who were suspected as diabetic retinopathy and admitted to the hospital between February 2015 and December 2016 were selected. They underwent direct ophthalmoscopy and FFA. The manifestation characteristics of FFA in the diagnosis of diabetic retinopathy were summarized. The two examination methods were compared. In the diagnosis with direct ophthalmoscopy, 375 eyes out of 500 eyes were diagnosed as diabetic retinopathy (75%); there were 74 eyes at stage I, 88 eyes at stage II, 92 eyes at stage III, 83 eyes of stage IV, 28 eyes of stage V and 10 eyes of stage VI. In the diagnosis with FFA, 465 eyes out of 500 eyes were diagnosed as diabetic retinopathy (93%); there were 94 eyes at stage I, 110 eyes at stage II, 112 at stage III, 92 eyes at stage IV, 41 eyes at stage V and 16 eyes at stage VI. The detection rate of diabetic retinopathy using FFA was significantly higher than that using direct ophthalmoscopy (P<0.05). FFA found that 316 eyes had non-proliferative retinopathy (67.96%), 75 eyes had pre-proliferative lesions (16.13%), 149 eyes had proliferative lesions (32.04%), 135 eyes had diabetic maculopathy (29.03%) and 31 eyes had diabetic optic disc lesions (6.67%). The detection rate of diabetic retinopathy using FFA is higher than that using direct ophthalmoscopy. FFA could accurately determine clinical stage. Therefore, it is an important approach in treatment efficacy evaluation and treatment guidance, suggesting a significant application value.

Fitting Vo-Ag and FFA Together Best for Students and Teachers.

ERIC Educational Resources Information Center

Snyder, H. Leon

1979-01-01

The Future Farmers of America (FFA) is more than a leadership development organization and when used as an intracurricular activity, it can serve as a teaching tool. The FFA adds advantages to the program in areas such as supervised experience, award motivation, providing real world experience, public relations, travel, and competition. (LRA)

Agrarianism: An Ideology of the National FFA Organization

ERIC Educational Resources Information Center

Martin, Michael J.; Kitchel, Tracy

2013-01-01

The traditions of the National FFA Organization (FFA) are grounded in agrarianism. This ideology focuses on the ability of farming and nature to develop citizens and integrity within people. Agrarianism has been an important thread of American rhetoric since the founding of country. The ideology has morphed over the last two centuries as the…

Contributions to the Development of State FFA Officers

ERIC Educational Resources Information Center

Hoover, Tracy S.; Bruce, Jacklyn A.

2006-01-01

What are the long term consequences associated with serving as a state FFA officer? Using a semi-structured interview format, selected state FFA officers from a twenty year time span were interviewed to assess their perceptions of and assets attributed to their experiences as a state officer. Results indicated that past state officers, regardless…

When Leadership Counts: Engaging Youth through the Washington Leadership Conference

ERIC Educational Resources Information Center

Stedman, Nicole L. P.; Rutherford, Tracy A.; Rosser, Manda H.; Elbert, Chanda

2009-01-01

The National FFA Organization continues to be a leader in the positive development of youth. Programs sponsored by the FFA provide youth with opportunities to develop their capacity for leadership and citizenship. The Washington Leadership Conference (WLC) is a weeklong conference during the summer that culminates the FFA experience. The WLC's…

Effects of Eucommia leaf extracts on autonomic nerves, body temperature, lipolysis, food intake, and body weight.

PubMed

Horii, Yuko; Tanida, Mamoru; Shen, Jiao; Hirata, Tetsuya; Kawamura, Naomi; Wada, Atsunori; Nagai, Katsuya

2010-08-02

Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Initiation and execution of lipotoxic ER stress in pancreatic β-cells

PubMed Central

Cunha, Daniel A.; Hekerman, Paul; Ladrière, Laurence; Bazarra-Castro, Angie; Ortis, Fernanda; Wakeham, Marion C.; Moore, Fabrice; Rasschaert, Joanne; Cardozo, Alessandra K.; Bellomo, Elisa; Overbergh, Lutgart; Mathieu, Chantal; Lupi, Roberto; Hai, Tsonwin; Herchuelz, Andre; Marchetti, Piero; Rutter, Guy A.; Eizirik, Décio L.; Cnop, Miriam

2013-01-01

Summary Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP. PMID:18559892

Beamspace fast fully adaptive brain source localization for limited data sequences

NASA Astrophysics Data System (ADS)

Ravan, Maryam

2017-05-01

In the electroencephalogram (EEG) or magnetoencephalogram (MEG) context, brain source localization methods that rely on estimating second order statistics often fail when the observations are taken over a short time interval, especially when the number of electrodes is large. To address this issue, in previous study, we developed a multistage adaptive processing called fast fully adaptive (FFA) approach that can significantly reduce the required sample support while still processing all available degrees of freedom (DOFs). This approach processes the observed data in stages through a decimation procedure. In this study, we introduce a new form of FFA approach called beamspace FFA. We first divide the brain into smaller regions and transform the measured data from the source space to the beamspace in each region. The FFA approach is then applied to the beamspaced data of each region. The goal of this modification is to benefit the correlation sensitivity reduction between sources in different brain regions. To demonstrate the performance of the beamspace FFA approach in the limited data scenario, simulation results with multiple deep and cortical sources as well as experimental results are compared with regular FFA and widely used FINE approaches. Both simulation and experimental results demonstrate that the beamspace FFA method can localize different types of multiple correlated brain sources in low signal to noise ratios more accurately with limited data.

Examining Year-Long Leadership Gains in FFA Members by Prior FFA Involvement, Class Year, and Gender

ERIC Educational Resources Information Center

Rosch, David; Simonsen, Jon C.; Velez, Jonathan J.

2015-01-01

Students (N = 160) in three diverse FFA chapters were surveyed in early fall, midwinter, and late spring in regard to their leadership skills, confidence in leading, and motivation to engage in leadership-oriented behaviors. The results indicated small-to-moderate gains in transformational leadership skill and a marginally significant…

The Benefits of FFA Membership as Part of Agricultural Education

ERIC Educational Resources Information Center

Rose, Chelsea; Stephens, Carrie A.; Stripling, Christopher; Cross, Tim; Sanok, Danielle E.; Brawner, Shelby

2016-01-01

The study sought to identify the benefits of FFA membership based on the fulfillment of three basic human needs: love and belonging, self-esteem, and self-actualization. The study focused on the fulfillment of FFA members' basic human needs as defined by Abraham Maslow. The three needs on which this study focused are: love and belonging,…

Engaging Hispanic Students in Agricultural Education and the FFA: A 3-Year Case Study

ERIC Educational Resources Information Center

Roberts, T. Grady; Hall, Johnathan L.; Briers, Gary E.; Gill, Ernie; Shinn, Glen C.; Larke, Alvin, Jr.; Jaure, Paul

2009-01-01

This article describes the outcomes of field-based efforts to increase diversity in agricultural education programs and the FFA. This study focused on three schools in San Antonio, Texas. Guided by Rogers' (2003) theories of diffusion of innovations, a series of six intervention strategies was implemented: (a) provide specific FFA or agricultural…

Youth Leadership Development: A National Analysis of FFA Member Role and Activity Context

ERIC Educational Resources Information Center

Peiter Horstmeier, Robin; Nall, Martha A.

2007-01-01

A purpose of youth organizations is to develop leadership skills among members through organizational structure and organization sponsored activities. But do they develop those skills? This national, multi-stage study examined the role of youth and the context of their activities in developing leadership in rural FFA chapters. FFA members had a…

A hybrid SVM-FFA method for prediction of monthly mean global solar radiation

NASA Astrophysics Data System (ADS)

Shamshirband, Shahaboddin; Mohammadi, Kasra; Tong, Chong Wen; Zamani, Mazdak; Motamedi, Shervin; Ch, Sudheer

2016-07-01

In this study, a hybrid support vector machine-firefly optimization algorithm (SVM-FFA) model is proposed to estimate monthly mean horizontal global solar radiation (HGSR). The merit of SVM-FFA is assessed statistically by comparing its performance with three previously used approaches. Using each approach and long-term measured HGSR, three models are calibrated by considering different sets of meteorological parameters measured for Bandar Abbass situated in Iran. It is found that the model (3) utilizing the combination of relative sunshine duration, difference between maximum and minimum temperatures, relative humidity, water vapor pressure, average temperature, and extraterrestrial solar radiation shows superior performance based upon all approaches. Moreover, the extraterrestrial radiation is introduced as a significant parameter to accurately estimate the global solar radiation. The survey results reveal that the developed SVM-FFA approach is greatly capable to provide favorable predictions with significantly higher precision than other examined techniques. For the SVM-FFA (3), the statistical indicators of mean absolute percentage error (MAPE), root mean square error (RMSE), relative root mean square error (RRMSE), and coefficient of determination ( R 2) are 3.3252 %, 0.1859 kWh/m2, 3.7350 %, and 0.9737, respectively which according to the RRMSE has an excellent performance. As a more evaluation of SVM-FFA (3), the ratio of estimated to measured values is computed and found that 47 out of 48 months considered as testing data fall between 0.90 and 1.10. Also, by performing a further verification, it is concluded that SVM-FFA (3) offers absolute superiority over the empirical models using relatively similar input parameters. In a nutshell, the hybrid SVM-FFA approach would be considered highly efficient to estimate the HGSR.

Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice.

PubMed

Fini, Lucia; Piazzi, Giulia; Ceccarelli, Claudio; Daoud, Yahya; Belluzzi, Andrea; Munarini, Alessandra; Graziani, Giulia; Fogliano, Vincenzo; Selgrad, Michael; Garcia, Melissa; Gasbarrini, Antonio; Genta, Robert M; Boland, C Richard; Ricciardiello, Luigi

2010-12-01

Although cyclooxygenase (COX)-2 inhibitors could represent the most effective chemopreventive tool against colorectal cancer (CRC), their use in clinical practice is hampered by cardiovascular side effects. Consumption of ω-3-polyunsaturated fatty acids (ω-3-PUFAs) is associated with a reduced risk of CRC. Therefore, in this study, we assessed the efficacy of a novel 99% pure preparation of ω-3-PUFA eicosapentaenoic acid as free fatty acids (EPA-FFA) on polyps in Apc(Min/+) mice. Apc(Min/+) and corresponding wild-type mice were fed control diet (Ctrl) or diets containing either EPA-FFA 2.5% or 5%, for 12 weeks while monitoring food intake and body weight. We found that both EPA-FFA diets protected from the cachexia observed among Apc(Min/+) animals fed Ctrl diet (P < 0.0054), without toxic effect, in conjunction with a significant decrease in lipid peroxidation in the treated arms. Moreover, both EPA-FFA diets dramatically suppressed polyp number (by 71.5% and 78.6%, respectively; P < 0.0001) and load (by 82.5% and 93.4%, respectively; P < 0.0001) in both small intestine and colon. In addition, polyps less than 1 mm in size were predominantly found in the EPA-FFA 5% arm whereas those 1 to 3 mm in size were more frequent in the Ctrl arm (P < 0.0001). Interestingly, in the EPA-FFA groups, mucosal arachidonic acid was replaced by EPA (P < 0.0001), leading to a significant reduction in COX-2 expression and β-catenin nuclear translocation. Moreover, in the EPA-FFA arms, we found a significant decrease in proliferation throughout the intestine together with an increase in apoptosis. Our data make 99% pure EPA-FFA an excellent candidate for CRC chemoprevention. ©2010 AACR.

Facile preparation of SERS and catalytically active Au nanostructures using furfuryl derivatives

NASA Astrophysics Data System (ADS)

Kim, Ki-Jung; Kim, Hyun-Chul; Park, Minsun; Huh, Seong

2017-08-01

Six different types of Au nanostructures with rough surfaces were readily prepared through the redox reactions between Au precursor, AuCl4-, and furfuryl derivatives without extra metal surface capping ligands, in deionized water at room temperature. Furfuryl alcohol (FA) or furfurylamine (FFA) was used as a sole reducing agent for the reduction of Au precursor. Both FA and FFA effectively polymerized during the redox reactions to form polyfuran polymers. These polymers are thought to act as surface capping ligands during the formation of Au nanostructures. Experiments were conducted with three different concentrations of each furfuryl derivative. Interestingly, Au particles prepared from the reaction with varying concentration of FA or FFA showed large differences in size, and revealed that the higher the ratios of [FA]/[AuCl4-] or [FFA]/[AuCl4-], the smaller the size of Au particles. The size of Au particles was in the range of 1 μm to under 30 nm. Among these samples, two nanostructured Au particles, AuFA-4 and AuFFA-1, deposited on a Si wafer by a simple drop-casting method, were revealed as highly active surface-enhanced Raman scattering (SERS) substrates for the detection of methylene blue (MB) and crystal violet (CV). High SERS enhancement factors (EFs) of 106 ∼ 108 for MB and CV were observed. Small size Au nanoparticles (AuFFA-2 and AuFFA-4) were also found to be very active for the catalytic hydrogenation of 4-nitrophenol to 4-aminophenol in the presence of NaBH4 at room temperature. AuFFA-2 could be recycled eight times, without losing its activity.

Changes in gene expression in PBMCs profiles of PPARα target genes in obese and non-obese individuals during fasting.

PubMed

Felicidade, Ingrid; Marcarini, Juliana Cristina; Carreira, Clísia Mara; Amarante, Marla Karine; Afman, Lydia A; Mantovani, Mário Sérgio; Ribeiro, Lúcia Regina

2015-01-01

The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Q-PCR was utilized to assess the mRNA expression levels of target genes. In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel.

Free fatty acid (FFA) and hydroxy carboxylic acid (HCA) receptors.

PubMed

Offermanns, Stefan

2014-01-01

Saturated and unsaturated free fatty acids (FFAs), as well as hydroxy carboxylic acids (HCAs) such as lactate and ketone bodies, are carriers of metabolic energy, precursors of biological mediators, and components of biological structures. However, they are also able to exert cellular effects through G protein-coupled receptors named FFA1-FFA4 and HCA1-HCA3. Work during the past decade has shown that these receptors are widely expressed in the human body and regulate the metabolic, endocrine, immune and other systems to maintain homeostasis under changing dietary conditions. The development of genetic mouse models and the generation of synthetic ligands of individual FFA and HCA receptors have been instrumental in identifying cellular and biological functions of these receptors. These studies have produced strong evidence that several FFA and HCA receptors can be targets for the prevention and treatment of various diseases, including type 2 diabetes mellitus, obesity, and inflammation.

The contribution of autochthonous microflora on free fatty acids release and flavor development in low-salt fermented fish.

PubMed

Xu, Yanshun; Li, Lin; Regenstein, Joe Mac; Gao, Pei; Zang, Jinhong; Xia, Wenshui; Jiang, Qixing

2018-08-01

To investigate the contribution of autochthonous microflora on free fatty acids (FFA) release and flavor development in low-salt fermented fish, three groups of processed fish, including bacteriostatic-acidification group (BAG), bacteriostatic group (BG), and spontaneous fermented fish (CG) were established. Results showed that addition of NaN 3 reduced microbial load in BAG and BG below 3.5 log CFU/g after 3 weeks of incubation. Activities of lipases and lipoxygenase declined markedly with increasing time, where BG had the highest activities, followed by CG and BAG. There is a 36.3% higher in the total FFA content in CG than that in BAG, indicating both microbial and endogenous lipases contributed to the FFA liberation in fermented fish while endogenous lipases play a major role. However, compared to BAG and BG, largely higher levels of volatile compounds were observed in CG, suggesting that autochthonous microflora dominated the generation of volatile flavor compounds in fermented fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

PubMed

Val-Laillet, David; Besson, Marie; Guérin, Sylvie; Coquery, Nicolas; Randuineau, Gwénaëlle; Kanzari, Ameni; Quesnel, Hélène; Bonhomme, Nathalie; Bolhuis, J Elizabeth; Kemp, Bas; Blat, Sophie; Le Huërou-Luron, Isabelle; Clouard, Caroline

2017-05-01

A suboptimal early nutritional environment ( i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs ( Sus scrofa ) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows ( n = 17) and their piglets ( n = 65), and on spatial cognition ( n = 51), hippocampal plasticity ( n = 17), and food preferences/motivation ( n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations ( P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets ( P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels ( P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet ( P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards ( P < 0.01). WD piglets had higher working memory ( P = 0.015) and reference memory ( P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer ( P = 0.03) and decreased neurogenesis ( P < 0.005), but increased cell proliferation ( P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs. © FASEB.

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes.

PubMed

Lund, Søren S; Tarnow, Lise; Frandsen, Merete; Smidt, Ulla M; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

2008-01-01

Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients. Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index < or = 27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions. Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0-6 h postprandially. Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.

Factors Influencing or Discouraging Secondary School Students' FFA Participation

ERIC Educational Resources Information Center

Phelps, Kirstin; Henry, Anna L.; Bird, William A.

2012-01-01

Modern adolescents are faced with a variety of choices regarding how to spend their free time. As recruitment and increased student participation continues to be a major priority of the National FFA Organization, it is essential to explore the reasons why students make the choice to become or not to become a member of FFA. This study was a part of…

Differential Development of Selectivity for Faces and Bodies in the Fusiform Gyrus

ERIC Educational Resources Information Center

Peelen, Marius V.; Glaser, Bronwyn; Vuilleumier, Patrik; Eliez, Stephan

2009-01-01

Viewing faces or bodies activates category-selective areas of visual cortex, including the fusiform face area (FFA), fusiform body area (FBA), and extrastriate body area (EBA). Here, using fMRI, we investigate the development of these areas, focusing on the right FFA and FBA. Despite the overlap of functionally defined FFA and FBA (54%-75%…

Theoretical Study on Free Fatty Acid Elimination Mechanism for Waste Cooking Oils to Biodiesel over Acid Catalyst.

PubMed

Wang, Kai; Zhang, Xiaochao; Zhang, Jilong; Zhang, Zhiqiang; Fan, Caimei; Han, Peide

2016-05-01

A theoretical investigation on the esterification mechanism of free fatty acid (FFA) in waste cooking oils (WCOs) has been carried out using DMol(3) module based on the density functional theory (DFT). Three potential pathways of FFA esterification reaction are designed to achieve the formation of fatty acid methyl ester (FAME), and calculated results show that the energy barrier can be efficiently reduced from 88.597kcal/mol to 15.318kcal/mol by acid catalyst. The molar enthalpy changes (ΔrHm°) of designed pathways are negative, indicating that FFA esterification reaction is an exothermic process. The obtained favorable energy pathway is: H(+) firstly activates FFA, then the intermediate combines with methanol to form a tetrahedral structure, and finally, producing FAME after removing a water molecule. The rate-determining step is the combination of the activated FFA with methanol, and the activation energy is about 11.513kcal/mol at 298.15K. Our results should provide basic and reliable theoretical data for further understanding the elimination mechanism of FFA over acid catalyst in the conversion of WCOs to biodiesel products. Copyright © 2016 Elsevier Inc. All rights reserved.

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

A Novel RSSI Prediction Using Imperialist Competition Algorithm (ICA), Radial Basis Function (RBF) and Firefly Algorithm (FFA) in Wireless Networks

PubMed Central

Goudarzi, Shidrokh; Haslina Hassan, Wan; Abdalla Hashim, Aisha-Hassan; Soleymani, Seyed Ahmad; Anisi, Mohammad Hossein; Zakaria, Omar M.

2016-01-01

This study aims to design a vertical handover prediction method to minimize unnecessary handovers for a mobile node (MN) during the vertical handover process. This relies on a novel method for the prediction of a received signal strength indicator (RSSI) referred to as IRBF-FFA, which is designed by utilizing the imperialist competition algorithm (ICA) to train the radial basis function (RBF), and by hybridizing with the firefly algorithm (FFA) to predict the optimal solution. The prediction accuracy of the proposed IRBF–FFA model was validated by comparing it to support vector machines (SVMs) and multilayer perceptron (MLP) models. In order to assess the model’s performance, we measured the coefficient of determination (R2), correlation coefficient (r), root mean square error (RMSE) and mean absolute percentage error (MAPE). The achieved results indicate that the IRBF–FFA model provides more precise predictions compared to different ANNs, namely, support vector machines (SVMs) and multilayer perceptron (MLP). The performance of the proposed model is analyzed through simulated and real-time RSSI measurements. The results also suggest that the IRBF–FFA model can be applied as an efficient technique for the accurate prediction of vertical handover. PMID:27438600

A Novel RSSI Prediction Using Imperialist Competition Algorithm (ICA), Radial Basis Function (RBF) and Firefly Algorithm (FFA) in Wireless Networks.

PubMed

Goudarzi, Shidrokh; Haslina Hassan, Wan; Abdalla Hashim, Aisha-Hassan; Soleymani, Seyed Ahmad; Anisi, Mohammad Hossein; Zakaria, Omar M

2016-01-01

This study aims to design a vertical handover prediction method to minimize unnecessary handovers for a mobile node (MN) during the vertical handover process. This relies on a novel method for the prediction of a received signal strength indicator (RSSI) referred to as IRBF-FFA, which is designed by utilizing the imperialist competition algorithm (ICA) to train the radial basis function (RBF), and by hybridizing with the firefly algorithm (FFA) to predict the optimal solution. The prediction accuracy of the proposed IRBF-FFA model was validated by comparing it to support vector machines (SVMs) and multilayer perceptron (MLP) models. In order to assess the model's performance, we measured the coefficient of determination (R2), correlation coefficient (r), root mean square error (RMSE) and mean absolute percentage error (MAPE). The achieved results indicate that the IRBF-FFA model provides more precise predictions compared to different ANNs, namely, support vector machines (SVMs) and multilayer perceptron (MLP). The performance of the proposed model is analyzed through simulated and real-time RSSI measurements. The results also suggest that the IRBF-FFA model can be applied as an efficient technique for the accurate prediction of vertical handover.

Role of free fatty acid receptors in the regulation of energy metabolism.

PubMed

Hara, Takafumi; Kashihara, Daiji; Ichimura, Atsuhiko; Kimura, Ikuo; Tsujimoto, Gozoh; Hirasawa, Akira

2014-09-01

Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores. FFARs can be grouped according to ligand profiles, depending on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41. However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84 receptor. A number of pharmacological and physiological studies have shown that these receptors are expressed in various tissues and are primarily involved in energy metabolism. Because an impairment of these processes is a part of the pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic targets. Here, we reviewed recently published studies on the physiological functions of these receptors, primarily focusing on energy homeostasis. Copyright © 2014 Elsevier B.V. All rights reserved.

Medical comorbidities in patients with lichen planopilaris, a retrospective case-control study.

PubMed

Fertig, Raymond M; Hu, Shasa; Maddy, Austin J; Balaban, Alexandra; Aleid, Nouf; Aldahan, Adam; Tosti, Antonella

2018-04-16

Lichen planopilaris (LPP) is a rare inflammatory lymphocyte-mediated disease of the scalp considered to have an autoimmune pathogenesis. To identify the prevalence of medical comorbidities in patients with classic LPP (CLPP) and frontal fibrosing alopecia (FFA). The medical records of 206 LPP patients and 323 control patients were retrospectively reviewed for existing comorbidities. The control group consisted of 257 patients with androgenetic alopecia (ICD 9 = 704.0 or ICD 10 = L64.9) and 66 patients with actinic keratosis (ICD 9 = 702.0 or ICD 10 = L57.0). Systemic lupus erythematosus (SLE) was found in 4.37% of all patients with LPP (including CLPP and the FFA subtype) and in 0.31% of controls. Female patients with the FFA subtype were more likely to have SLE than controls (OR 31.034, 95% CI 2.405-400.382, P = 0.0085). This study is limited in that it is a retrospective chart review. Female patients with FFA are significantly more likely to have SLE. Patients with LPP (including CLPP and the FFA subtype) are less likely to have diabetes. Patients with CLPP excluding FFA are less likely to have hypertension, heart disease, and hypothyroidism. © 2018 The International Society of Dermatology.

Lecithin inhibits fatty acid and bile salt absorption from rat small intestine in vivo.

PubMed

Saunders, D R; Sillery, J

1976-12-01

During digestion of a fatty meal, long chain free fatty acids (FFA) and lecithin are among the lipids solubilized in intestinal contents as mixed micelles with bile salts. We hypothesized that if lecithin were not hydrolyzed, the mixed micelles would be abnormal, and absorption of FFA and bile salts would be depressed. To test this hypothesis, isolated segments of rat small intestine were infused in vivo with micellar solutions of 2 mMolar linoleic acid and 10 mMolar taurocholate to which was added 3 mMolar 1-palmitoyl, 2-oleoyl lecithin (a common lecithin in bile and food), or 1-palmitoyl lysolecithin (the hydrolytic product of lecithin). Absorption of FFA and bile salt was measured under steady state conditions using a single-pass technique. Lecithin depressed the rate of FFA absorption by 40% (p less than 0.025) in jejunal and ileal segments whereas lysolecithin was associated with normal rates of FFA absorption. Lecithin also reduced taurocholate absorption from the ileum by 30% (p less than 0.05). These data support the idea that lecithin may depress FFA and bile salt absorption from the small intestine in pancreatic insufficiency.

Consecutive TMS-fMRI reveals remote effects of neural noise to the "occipital face area".

PubMed

Solomon-Harris, Lily M; Rafique, Sara A; Steeves, Jennifer K E

2016-11-01

The human cortical system for face perception comprises a network of connected regions including the middle fusiform gyrus ("fusiform face area" or FFA), the inferior occipital gyrus ("occipital face area" or OFA), and the posterior superior temporal sulcus (pSTS). Here, we sought to investigate how transcranial magnetic stimulation (TMS) to the OFA affects activity within the face processing network. We used offline repetitive TMS to temporarily introduce neural noise in the right OFA in healthy subjects. We then immediately performed functional magnetic resonance imaging (fMRI) to measure changes in blood oxygenation level dependent (BOLD) signal across the face network using an fMR-adaptation (fMR-A) paradigm. We hypothesized that TMS to the right OFA would induce abnormal face identity coding throughout the face processing network in regions to which it has direct or indirect connections. Indeed, BOLD signal for face identity, but not non-face (butterfly) identity, decreased in the right OFA and FFA following TMS to the right OFA compared to both sham TMS and TMS to a control site, the nearby object-related lateral occipital area (LO). Further, TMS to the right OFA decreased face-related activation in the left FFA, without any effect in the left OFA. Our findings indicate that TMS to the right OFA selectively disrupts face coding at both the stimulation site and bilateral FFA. TMS to the right OFA also decreased BOLD signal for different identity stimuli in the right pSTS. Together with mounting evidence from patient studies, we demonstrate connectivity of the OFA within the face network and that its activity modulates face processing in bilateral FFA as well as the right pSTS. Moreover, this study shows that deep regions within the face network can be remotely probed by stimulating structures closer to the cortical surface. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipid structure does not modify incorporation of EPA and DHA into blood lipids in healthy adults: a randomised-controlled trial.

PubMed

West, Annette L; Burdge, Graham C; Calder, Philip C

2016-09-01

Dietary supplementation is an effective means to improve EPA and DHA status. However, it is unclear whether lipid structure affects EPA+DHA bioavailability. We determined the effect of consuming different EPA and DHA lipid structures on their concentrations in blood during the postprandial period and during dietary supplementation compared with unmodified fish oil TAG (uTAG). In a postprandial cross-over study, healthy men (n 9) consumed in random order test meals containing 1·1 g EPA+0·37 g DHA as either uTAG, re-esterified TAG, free fatty acids (FFA) or ethyl esters (EE). In a parallel design supplementation study, healthy men and women (n 10/sex per supplement) consumed one supplement type for 12 weeks. Fatty acid composition was determined by GC. EPA incorporation over 6 h into TAG or phosphatidylcholine (PC) did not differ between lipid structures. EPA enrichment in NEFA was lower from EE than from uTAG (P=0·01). Plasma TAG, PC or NEFA DHA incorporation did not differ between lipid structures. Lipid structure did not affect TAG or NEFA EPA incorporation and PC or NEFA DHA incorporation following dietary supplementation. Plasma TAG peak DHA incorporation was greater (P=0·02) and time to peak shorter (P=0·02) from FFA than from uTAG in men. In both studies, the order of EPA and DHA incorporation was PC>TAG>NEFA. In conclusion, EPA and DHA lipid structure may not be an important consideration in dietary interventions.

Process audits versus product quality monitoring of bulk milk.

PubMed

Velthuis, A G J; van Asseldonk, M A P M

2011-01-01

Assessment of milk quality is based on bulk milk testing and farm certification on process quality audits. It is unknown to what extent dairy farm audits improve milk quality. A statistical analysis was conducted to quantify possible associations between bulk milk testing and dairy farm audits. The analysis comprised 64.373 audit outcomes on 26,953 dairy farms, which were merged with all conducted laboratory tests of bulk milk samples 12 mo before the audit. Each farm audit record included 271 binary checklist items and 52 attention point variables (given to farmers if serious deviations were observed), both indicating possible deviations from the desired farm situation. Test results included somatic cell count (SCC), total bacterial count (TBC), antimicrobial drug residues (ADR), level of butyric acid spores (BAB), freezing point depression (FPD), level of free fatty acid (FFA), and milk sediment (SED). Results show that numerous audit variables were related to bulk milk test results, although the goodness of fit of the models was generally low. Cow hygiene, clean cubicles, hygiene of milking parlor, and utility room were positively correlated with superior product quality, mainly with respect to SCC, TBC, BAB, FPD, FFA, and SED. Animal health or veterinary drugs management (i.e., drug treatment recording, marking of treated animals, and storage of veterinary drugs) related to SCC, FPD, FFA, and SED. The availability of drinking water was related to TBC, BAB, FFA, and SED, whereas maintenance of the milking equipment was related mainly to SCC, FPD, and FFA. In summary, bulk milk quality and farm audit outcomes are, to some degree, associated: if dairy farms are assessed negatively on specific audit aspects, the bulk milk quality is more likely to be inferior. However, the proportion of the total variance in milk test results explained by audits ranged between 4 and 13% (depending on the specific bulk milk test), showing that auditing dairy farms provides additional information but has a limited association with the outcome of a product quality control program. This study suggests that farm audits could be streamlined to include only relevant checklist items and that bulk milk quality monitoring could be used as a basis of selecting farms for more or less frequent audits. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Design optimization of steel frames using an enhanced firefly algorithm

NASA Astrophysics Data System (ADS)

Carbas, Serdar

2016-12-01

Mathematical modelling of real-world-sized steel frames under the Load and Resistance Factor Design-American Institute of Steel Construction (LRFD-AISC) steel design code provisions, where the steel profiles for the members are selected from a table of steel sections, turns out to be a discrete nonlinear programming problem. Finding the optimum design of such design optimization problems using classical optimization techniques is difficult. Metaheuristic algorithms provide an alternative way of solving such problems. The firefly algorithm (FFA) belongs to the swarm intelligence group of metaheuristics. The standard FFA has the drawback of being caught up in local optima in large-sized steel frame design problems. This study attempts to enhance the performance of the FFA by suggesting two new expressions for the attractiveness and randomness parameters of the algorithm. Two real-world-sized design examples are designed by the enhanced FFA and its performance is compared with standard FFA as well as with particle swarm and cuckoo search algorithms.

Bicellar systems as a new colloidal delivery strategy for skin.

PubMed

Rubio, L; Rodríguez, G; Barbosa-Barros, L; Alonso, C; Cócera, M; de la Maza, A; Parra, J L; López, O

2012-04-01

The presented work evaluates the use of bicellar systems as new delivery vectors for controlled release of compounds through the skin. Two different active principles were introduced into the bicellar systems: diclofenac diethylamine (DDEA) and flufenamic acid (Ffa). Bicellar systems are discoidal aggregates formed by long and short alkyl chain phospholipids. Characterization of the bicellar systems by dynamic light scattering (DLS) and cryogenic transmission electron microscopy (Cryo-TEM) showed that particle size decreased when DDEA was encapsulated and increased when Ffa was included in the bicellar systems. Percutaneous absorption studies demonstrated a lower penetration of DDEA and Ffa through the skin when the drugs were included in the bicellar systems than when the drugs were applied in an aqueous solution (DDEA) and in an ethanolic solution (Ffa); the reduction in penetration was more pronounced with Ffa. These bicellar systems may have retardant effects on percutaneous absorption, which result in a promising strategy for future drug or cosmetic delivery applications. Copyright © 2011 Elsevier B.V. All rights reserved.

Dynamic Encoding of Face Information in the Human Fusiform Gyrus

PubMed Central

Ghuman, Avniel Singh; Brunet, Nicolas M.; Li, Yuanning; Konecky, Roma O.; Pyles, John A.; Walls, Shawn A.; Destefino, Vincent; Wang, Wei; Richardson, R. Mark

2014-01-01

Humans’ ability to rapidly and accurately detect, identify, and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing, however temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly upon FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200-500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses. PMID:25482825

Dynamic encoding of face information in the human fusiform gyrus.

PubMed

Ghuman, Avniel Singh; Brunet, Nicolas M; Li, Yuanning; Konecky, Roma O; Pyles, John A; Walls, Shawn A; Destefino, Vincent; Wang, Wei; Richardson, R Mark

2014-12-08

Humans' ability to rapidly and accurately detect, identify and classify faces under variable conditions derives from a network of brain regions highly tuned to face information. The fusiform face area (FFA) is thought to be a computational hub for face processing; however, temporal dynamics of face information processing in FFA remains unclear. Here we use multivariate pattern classification to decode the temporal dynamics of expression-invariant face information processing using electrodes placed directly on FFA in humans. Early FFA activity (50-75 ms) contained information regarding whether participants were viewing a face. Activity between 200 and 500 ms contained expression-invariant information about which of 70 faces participants were viewing along with the individual differences in facial features and their configurations. Long-lasting (500+ms) broadband gamma frequency activity predicted task performance. These results elucidate the dynamic computational role FFA plays in multiple face processing stages and indicate what information is used in performing these visual analyses.

Activity in the fusiform face area supports expert perception in radiologists and does not depend upon holistic processing of images

NASA Astrophysics Data System (ADS)

Engel, Stephen A.; Harley, Erin M.; Pope, Whitney B.; Villablanca, J. Pablo; Mazziotta, John C.; Enzmann, Dieter

2009-02-01

Training in radiology dramatically changes observers' ability to process images, but the neural bases of this visual expertise remain unexplored. Prior imaging work has suggested that the fusiform face area (FFA), normally selectively responsive to faces, becomes responsive to images in observers' area of expertise. The FFA has been hypothesized to be important for "holistic" processing that integrates information across the entire image. Here, we report a cross-sectional study of radiologists that used functional magnetic resonance imaging to measure neural activity in first-year radiology residents, fourth-year radiology residents, and practicing radiologists as they detected abnormalities in chest radiographs. Across subjects, activity in the FFA correlated with visual expertise, measured as behavioral performance during scanning. To test whether processing in the FFA was holistic, we measured its responses both to intact radiographs and radiographs that had been divided into 25 square pieces whose locations were scrambled. Activity in the FFA was equal in magnitude for intact and scrambled images, and responses to both kinds of stimuli correlated reliably with expertise. These results suggest that the FFA is one of the cortical regions that provides the basis of expertise in radiology, but that its contribution is not holistic processing of images.

The role of the fusiform face area in social cognition: implications for the pathobiology of autism.

PubMed Central

Schultz, Robert T; Grelotti, David J; Klin, Ami; Kleinman, Jamie; Van der Gaag, Christiaan; Marois, René; Skudlarski, Pawel

2003-01-01

A region in the lateral aspect of the fusiform gyrus (FG) is more engaged by human faces than any other category of image. It has come to be known as the 'fusiform face area' (FFA). The origin and extent of this specialization is currently a topic of great interest and debate. This is of special relevance to autism, because recent studies have shown that the FFA is hypoactive to faces in this disorder. In two linked functional magnetic resonance imaging (fMRI) studies of healthy young adults, we show here that the FFA is engaged by a social attribution task (SAT) involving perception of human-like interactions among three simple geometric shapes. The amygdala, temporal pole, medial prefrontal cortex, inferolateral frontal cortex and superior temporal sulci were also significantly engaged. Activation of the FFA to a task without faces challenges the received view that the FFA is restricted in its activities to the perception of faces. We speculate that abstract semantic information associated with faces is encoded in the FG region and retrieved for social computations. From this perspective, the literature on hypoactivation of the FFA in autism may be interpreted as a reflection of a core social cognitive mechanism underlying the disorder. PMID:12639338

Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury.

PubMed

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2014-04-01

Carbon tetrachloride (CCl4) is a potent hepatotoxic agent causing hepatic necrosis and it is widely used in animal models for induction of acute and chronic liver damage. The antioxidative and hepatoprotective effects of chitosan from Sepia kobiensis against CCl4 induced liver toxicity in Wistar rats was studied by measuring the activity of lipid peroxidation (TBARS, lipid hydroperoxides), non enzymatic antioxidant (GSH), antioxidant enzyme activities (SOD, CAT and GPx), liver marker enzymes (ALT and AST), lipid profile (FFA, TG, cholesterol and HDL cholesterol) and histopathological changes. Rats treated with chitosan against CCl4 toxicity showed significantly decreased levels of ALT and AST activities, total cholesterol, triglyceride and free fatty acid in plasma and tissue. Whereas the treatment with chitosan along with CCl4 showed markedly increased level of hepatic and circulatory in SOD, CAT, GPx and reduced glutathione and decreased the malondialdehyde level. Histopathological observations proved the marked hepatoprotective effect of chitosan. The CCl4 induced alterations in circulatory and hepatic antioxidant defense system were normalized by chitosan and it could be concluded that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity.

PubMed

Yokoyama, Kunihiro; Tatsumi, Yasuaki; Hayashi, Kazuhiko; Goto, Hidemi; Ishikawa, Tetsuya; Wakusawa, Shinya

2017-01-01

In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate. The level of ROS was quantified using 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA), and the activation of the PI3K/Akt signaling pathway was determined by Western blotting assay using appropriate antibodies. The intracellular ROS levels were increased by palmitate but were reduced by treatment with UDCA and insulin. Furthermore, insulin significantly stimulated the phosphorylation of Akt. When the cells were pre-treated with palmitate, insulin-induced Akt-phosphorylation was markedly inhibited. However, when the cells were treated with palmitate and UDCA, the effects of insulin were partially restored. UDCA may have protective effects against palmitate-induced decreases in responsiveness to insulin.

Metabolic Effects of Chronic Cannabis Smoking

PubMed Central

Muniyappa, Ranganath; Sable, Sara; Ouwerkerk, Ronald; Mari, Andrea; Gharib, Ahmed M.; Walter, Mary; Courville, Amber; Hall, Gail; Chen, Kong Y.; Volkow, Nora D.; Kunos, George; Huestis, Marilyn A.; Skarulis, Monica C.

2013-01-01

OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT). RESULTS Self-reported cannabis use was: 9.5 (2–38) years; joints/day: 6 (3–30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups. CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance. PMID:23530011

High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance

PubMed Central

McGugin, Rankin Williams; Gatenby, J. Christopher; Gore, John C.; Gauthier, Isabel

2012-01-01

The fusiform face area (FFA) is a region of human cortex that responds selectively to faces, but whether it supports a more general function relevant for perceptual expertise is debated. Although both faces and objects of expertise engage many brain areas, the FFA remains the focus of the strongest modular claims and the clearest predictions about expertise. Functional MRI studies at standard-resolution (SR-fMRI) have found responses in the FFA for nonface objects of expertise, but high-resolution fMRI (HR-fMRI) in the FFA [Grill-Spector K, et al. (2006) Nat Neurosci 9:1177–1185] and neurophysiology in face patches in the monkey brain [Tsao DY, et al. (2006) Science 311:670–674] reveal no reliable selectivity for objects. It is thus possible that FFA responses to objects with SR-fMRI are a result of spatial blurring of responses from nonface-selective areas, potentially driven by attention to objects of expertise. Using HR-fMRI in two experiments, we provide evidence of reliable responses to cars in the FFA that correlate with behavioral car expertise. Effects of expertise in the FFA for nonface objects cannot be attributed to spatial blurring beyond the scale at which modular claims have been made, and within the lateral fusiform gyrus, they are restricted to a small area (200 mm2 on the right and 50 mm2 on the left) centered on the peak of face selectivity. Experience with a category may be sufficient to explain the spatially clustered face selectivity observed in this region. PMID:23027970

Free fatty acid receptor 3 is a key target of short chain fatty acid. What is the impact on the sympathetic nervous system?

PubMed

López Soto, Eduardo Javier; Gambino, Luisina Ongaro; Mustafá, Emilio Román

2014-01-01

Nervous system (NS) activity participates in metabolic homeostasis by detecting peripheral signal molecules derived from food intake and energy balance. High quality diets are thought to include fiber-rich foods like whole grain rice, breads, cereals, and grains. Several studies have associated high consumption of fiber-enriched diets with a reduced risk of diabetes, obesity, and gastrointestinal disorders. In the lower intestine, anaerobic fermentation of soluble fibers by microbiota produces short chain fatty acids (SCFAs), key energy molecules that have a recent identified leading role in the intestinal gluconeogenesis, promoting beneficial effects on glucose tolerance and insulin resistance. SCFAs are also signaling molecules that bind to specific G-protein coupled receptors (GPCRs) named Free Fatty Acid Receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43). However, how SCFAs impact NS activity through their GPCRs is poorly understood. Recently, studies have demonstrated the presence of FFA2 and FFA3 in the sympathetic NS of rat, mouse and human. Two studies have showed that FFA3 activation by SCFAs increases firing and norepinephrine (NE) release from sympathetic neurons. However, the recent study from the Ikeda Laboratory revealed that activation of FFA3 by SCFAs impairs N-type calcium channel (NTCC) activity, which contradicts the idea of FFA3 activation leading to increased action potential evoked NE release. Here we will discuss the scope of the latter study and the putative physiological role of SCFAs and FFAs in the sympathetic NS.

High-resolution imaging of expertise reveals reliable object selectivity in the fusiform face area related to perceptual performance.

PubMed

McGugin, Rankin Williams; Gatenby, J Christopher; Gore, John C; Gauthier, Isabel

2012-10-16

The fusiform face area (FFA) is a region of human cortex that responds selectively to faces, but whether it supports a more general function relevant for perceptual expertise is debated. Although both faces and objects of expertise engage many brain areas, the FFA remains the focus of the strongest modular claims and the clearest predictions about expertise. Functional MRI studies at standard-resolution (SR-fMRI) have found responses in the FFA for nonface objects of expertise, but high-resolution fMRI (HR-fMRI) in the FFA [Grill-Spector K, et al. (2006) Nat Neurosci 9:1177-1185] and neurophysiology in face patches in the monkey brain [Tsao DY, et al. (2006) Science 311:670-674] reveal no reliable selectivity for objects. It is thus possible that FFA responses to objects with SR-fMRI are a result of spatial blurring of responses from nonface-selective areas, potentially driven by attention to objects of expertise. Using HR-fMRI in two experiments, we provide evidence of reliable responses to cars in the FFA that correlate with behavioral car expertise. Effects of expertise in the FFA for nonface objects cannot be attributed to spatial blurring beyond the scale at which modular claims have been made, and within the lateral fusiform gyrus, they are restricted to a small area (200 mm(2) on the right and 50 mm(2) on the left) centered on the peak of face selectivity. Experience with a category may be sufficient to explain the spatially clustered face selectivity observed in this region.

Kinetics study of Jatropha oil esterification with ethanol in the presence of tin (II) chloride catalyst for biodiesel production

NASA Astrophysics Data System (ADS)

Kusumaningtyas, Ratna Dewi; Ratrianti, Naomi; Purnamasari, Indah; Budiman, Arief

2017-01-01

Jatropha oil is one of the promising feedstocks for biodiesel production. Jatropha oil is non-edible oil hence utilization of this oil would not compete with the needs of food. However, crude jatropha oil usually has high free fatty acid (FFA) content. Due to this fact, direct alkaline-catalyzed transesterification of crude jatropha oil for biodiesel production cannot be performed. FFA in crude jatropha oil will react with a base catalyst, resulting in soap as by product and hindering methyl ester (biodiesel) production. Therefore, prior to a transesterification reaction, it is crucial to run a pretreatment step of jatropha oil which can lower the FFA content in the oil. In this work, the pretreatment process was conducted through the esterification reaction of FFA contained in crude jatropha oil with ethanol over tin (II) chloride catalyst to reduce the acid value of the feedstock. The feedstock was Indonesia crude jatropha oil containing 12.03% of FFA. The esterification reaction was carried out in a batch reactor with a molar ratio of FFA to ethanol was 1:60 and total reaction time was 180 minutes. Tin (II) chloride catalyst was varied at 2.5, 5, 7.5, and 10% wt, whereas the effect of the reaction temperature was studied at 35, 34, 55, and 65 °C. The best reaction conversion was 71.55%, achieved at the following condition: a reaction temperature of 65 °C, catalyst concentration of 10% wt, the reaction time of 180 min, and the molar ratio of FFA to ethanol was 1:60. Kinetics study was also conducted in this work. It was found that esterification reaction of jatropha oil FFA with ethanol catalyzed by tin(II) chloride fitted the first-order pseudo-homogeneous kinetics model. It was also revealed that the frequency factor (A) and the activation energy (Ea) were 4.3864 × 106 min-1 and 56.2513 kJ/mole, respectively.

Frontal Fibrosing Alopecia and Vitiligo: Coexistence or True Association?

PubMed

Katoulis, Alexandros C; Diamanti, Konstantina; Sgouros, Dimitrios; Liakou, Aikaterini I; Alevizou, Antigoni; Bozi, Evangelia; Damaskou, Vasileia; Panayiotides, Ioannis; Rigopoulos, Dimitrios

2017-01-01

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia characterized by a progressive band-like recession of the frontotemporal hairline and frequent loss of the eyebrows. It predominantly affects postmenopausal women. Coexistence of FFA and vitiligo is rarely reported in the literature. We retrospectively studied 20 cases diagnosed with FFA in a 14-month period in our Department. Among them, there were 2 cases, a 72-year-old woman and a 48-year-old man, who developed FFA on preexisting vitiligo of the forehead. Anatomical colocalization of the two dermatoses supports the notion that a causal link may exist and their association may not be coincidental. We suggest that interrelated immunologic events and pathologic processes may underlie both these skin conditions.

[Two cases of frontal fibrosing alopecia in postmenopausal women].

PubMed

Herrmann, Anke; Bormann, Gisela; Marsch, Wolfgang Christian; Wohlrab, Johannes

2004-08-01

Frontal fibrosing alopecia (FFA) is an uncommon, slowly progressive, cicatricial alopecia which mainly affects postmenopausal women. It is considered to be a variant of lichen planopilaris. We describe two postmenopausal women who developed over 11 and 24 months an asymptomatic atrophic alopecia, restricted to the frontal hairline. The diagnosis of FFA was confirmed by biopsy showing a perifollicular lymphocytic infiltrate with fibrosis. Topical corticosteroids, in one case combined with minoxidil, administered for 3 months arrested the hair loss. The treatment of FFA is often difficult. In most cases, the disease resolves spontaneously after several years. Immunomodulators such as corticosteroids and calcineurin antagonists should be tried in the early stage of FFA (frontal effluvium with perifollicular erythema) in order to arrest the disease in its inflammatory phase.

Association of Temperament and Acute Stress Responsiveness with Productivity, Feed Efficiency, and Methane Emissions in Beef Cattle: An Observational Study

PubMed Central

Llonch, Pol; Somarriba, Miguel; Duthie, Carol-Anne; Haskell, Marie J.; Rooke, John A.; Troy, Shane; Roehe, Rainer; Turner, Simon P.

2016-01-01

The aim of this study was to assess individual differences in temperament and stress response and quantify their impact on feed efficiency, performance, and methane (CH4) emissions in beef cattle. Eighty-four steers (castrated males) (Charolais or Luing) were used. Temperament was assessed using two standardized tests: restlessness when restrained [crush score (CS)] and flight speed (FS) on release from restraint. Over a 56-day period individual animal dry matter intake (DMI) and weekly body weight was measured. Ultrasound fat depth was measured at the end of 56 days. Average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) were calculated. After the 56-day test period, animals were transported in groups of six/week to respiration chamber facilities. Blood samples were taken before and 0, 3, 6, and 9 h after transport. Plasma cortisol, creatine kinase (CK), glucose, and free fatty acids (FFA) were determined to assess physiological stress response. Subsequently, CH4 emissions were measured over a 3-day period in individual respiration chambers. CS (1.7 ± 0.09) and FS (1.6 ± 0.60 m/s) were repeatable (0.63 and 0.51, respectively) and correlated (r = 0.36, P < 0.001). Plasma cortisol, CK, and FFA concentrations increased after transport (P = 0.038, P = 0.006, and P < 0.001, respectively). Temperament (CS) and CK concentration were correlated (r = 0.29; P = 0.015). The extreme group analysis reveals that excitable animals (FS; P = 0.032) and higher stress response (cortisol, P = 0.007; FFA, P = 0.007; and CK, P = 0.003) were associated with lower DMI. ADG was lower in more temperamental animals (CS, P = 0.097, and FS, P = 0.030). Fat depth was greater in steers showing calmer CS (P = 0.026) and lower plasma CK (P = 0.058). Temperament did not show any relationship with RFI or CH4 emissions. However, steers with higher cortisol showed improved feed efficiency (lower FCR and RFI) (P < 0.05) and greater CH4 emissions (P = 0.017). In conclusion, agitated temperament and higher stress responsiveness is detrimental to productivity. A greater stress response is associated with a reduction in feed intake that may both increase the efficiency of consumed feed and the ratio of CH4 emissions/unit of feed. Therefore, temperament and stress response should be considered when designing strategies to improve efficiency and mitigate CH4 emissions in beef cattle. PMID:27379246

Association of Temperament and Acute Stress Responsiveness with Productivity, Feed Efficiency, and Methane Emissions in Beef Cattle: An Observational Study.

PubMed

Llonch, Pol; Somarriba, Miguel; Duthie, Carol-Anne; Haskell, Marie J; Rooke, John A; Troy, Shane; Roehe, Rainer; Turner, Simon P

2016-01-01

The aim of this study was to assess individual differences in temperament and stress response and quantify their impact on feed efficiency, performance, and methane (CH4) emissions in beef cattle. Eighty-four steers (castrated males) (Charolais or Luing) were used. Temperament was assessed using two standardized tests: restlessness when restrained [crush score (CS)] and flight speed (FS) on release from restraint. Over a 56-day period individual animal dry matter intake (DMI) and weekly body weight was measured. Ultrasound fat depth was measured at the end of 56 days. Average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) were calculated. After the 56-day test period, animals were transported in groups of six/week to respiration chamber facilities. Blood samples were taken before and 0, 3, 6, and 9 h after transport. Plasma cortisol, creatine kinase (CK), glucose, and free fatty acids (FFA) were determined to assess physiological stress response. Subsequently, CH4 emissions were measured over a 3-day period in individual respiration chambers. CS (1.7 ± 0.09) and FS (1.6 ± 0.60 m/s) were repeatable (0.63 and 0.51, respectively) and correlated (r = 0.36, P < 0.001). Plasma cortisol, CK, and FFA concentrations increased after transport (P = 0.038, P = 0.006, and P < 0.001, respectively). Temperament (CS) and CK concentration were correlated (r = 0.29; P = 0.015). The extreme group analysis reveals that excitable animals (FS; P = 0.032) and higher stress response (cortisol, P = 0.007; FFA, P = 0.007; and CK, P = 0.003) were associated with lower DMI. ADG was lower in more temperamental animals (CS, P = 0.097, and FS, P = 0.030). Fat depth was greater in steers showing calmer CS (P = 0.026) and lower plasma CK (P = 0.058). Temperament did not show any relationship with RFI or CH4 emissions. However, steers with higher cortisol showed improved feed efficiency (lower FCR and RFI) (P < 0.05) and greater CH4 emissions (P = 0.017). In conclusion, agitated temperament and higher stress responsiveness is detrimental to productivity. A greater stress response is associated with a reduction in feed intake that may both increase the efficiency of consumed feed and the ratio of CH4 emissions/unit of feed. Therefore, temperament and stress response should be considered when designing strategies to improve efficiency and mitigate CH4 emissions in beef cattle.

Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats.

PubMed

Gao, Yu; Song, Guang-Yao; Ma, Hui-Juan; Zhang, Wen-Jie; Zhou, Yu

2007-06-25

The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n=14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total triglyceride (TG), free fatty acid (FFA), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO2(-)/NO3(-)) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L-arginine (L-Arg), N(omega)-nitro-L-arginine (L-NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 micromol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P<0.05). It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P<0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P<0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L-Arg and decreased when incubated with L-NNA and MB in both high-fatty acid diet groups (P<0.05, P<0.01). But no difference was found before and after incubation with L-Arg, L-NNA and MB in the control rats. In the mean time, endothelium-independent maximal vasorelaxation response of renal arteries to NTP and renal arterial contractile responses to cumulative dose of NA were assayed, and there was no difference among the three groups (P>0.05). Endothelium-dependent vasorelaxation was negatively correlated with systolic blood pressure and TG, and positively correlated with NO2(-)/NO3(-) and GIR. There was a significantly negative correlation between FFA and NO2(-)/NO3(-). The present study suggests that both high-saturated and unsaturated fatty acid diets result in hypertension associated with significantly decreased endothelium-dependent vasorelaxation, dyslipidemia and IR, and that decreased endothelium-dependent vasorelaxation induced by high fatty acid diets is associated with impaired L-Arg-NO-cGMP pathways.

[Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes].

PubMed

Zou, Xin; Liu, De-Liang; Lu, Fu-Er; Dong, Hui; Xu, Li-Jun; Luo, Yun-Huan; Wang, Kai-Fu

2014-06-01

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats.

PubMed

Said, Hyder; Akiba, Yasutada; Narimatsu, Kazuyuki; Maruta, Koji; Kuri, Ayaka; Iwamoto, Ken-Ichi; Kuwahara, Atsukazu; Kaunitz, Jonathan D

2017-08-01

Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO 3 - secretion. We thus investigated the effects of synthetic selective FFA3 agonists with consequent GLP-2 release on NSAID-induced enteropathy. We measured duodenal HCO 3 - secretion in isoflurane-anesthetized rats in a duodenal loop perfused with the selective FFA3 agonists MQC or AR420626 (AR) while measuring released GLP-2 in the portal vein (PV). Intestinal injury was produced by indomethacin (IND, 10 mg/kg, sc) with or without MQC (1-10 mg/kg, ig) or AR (0.01-0.1 mg/kg, ig or ip) treatment. Luminal perfusion with MQC or AR (0.1-10 µM) dose-dependently augmented duodenal HCO 3 - secretion accompanied by increased GLP-2 concentrations in the PV. The effect of FFA3 agonists was inhibited by co-perfusion of the selective FFA3 antagonist CF3-MQC (30 µM). AR-induced augmented HCO 3 - secretion was reduced by iv injection of the GLP-2 receptor antagonist GLP-2(3-33) (3 nmol/kg), or by pretreatment with the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR inh -172 (1 mg/kg, ip). IND-induced small intestinal ulcers were dose-dependently inhibited by intragastric administration of MQC or AR. GLP-2(3-33) (1 mg/kg, ip) or CF3-MQC (1 mg/kg, ig) reversed AR-associated reduction in IND-induced enteropathy. In contrast, ip injection of AR had no effect on enteropathy. These results suggest that luminal FFA3 activation enhances mucosal defenses and prevents NSAID-induced enteropathy via the GLP-2 pathway. The selective FFA3 agonist may be a potential therapeutic candidate for NSAID-induced enteropathy.

A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice.

PubMed

Sairyo, Masami; Kobayashi, Takuya; Masuda, Daisaku; Kanno, Koutaro; Zhu, Yinghong; Okada, Takeshi; Koseki, Masahiro; Ohama, Tohru; Nishida, Makoto; Sakata, Yasushi; Yamashita, Shizuya

2018-02-01

Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism. Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups. Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate. K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.

ω-3 Polyunsaturated fatty acids accelerate airway repair by activating FFA4 in club cells.

PubMed

Lee, Kyoung-Pil; Park, Soo-Jin; Kang, Saeromi; Koh, Jung-Min; Sato, Koichi; Chung, Hae-Young; Okajima, Fumikazu; Im, Dong-Soon

2017-06-01

A G protein-coupled receptor (GPCR) named free fatty acid receptor 4 (FFA4, also known as GPR120) was found to act as a GPCR for ω-3 polyunsaturated fatty acids. Its expression has been reported in lung epithelial club cells. We investigated whether supplementation of the ω-3 fatty acids benefits lung health. Omacor (7.75 mg/kg), clinically prescribed preparation of ω-3 fatty acids, and FFA4-knockout mice were utilized in a naphthalene-induced mouse model of acute airway injury (1 injection of 30 mg/kg ip). Naphthalene injection induced complete destruction of bronchiolar epithelial cells within a day. Appearance of bronchiolar epithelial cells was observed after 21 days in control mice. It was found, however, that supplementation of Omacor accelerated the recovery. The appearance of bronchiolar epithelial cells was observed between 7 and 14 days after naphthalene injury in Omacor-treated mice. In isolated club cells, ω-3 fatty acids were found to stimulate cell proliferation and migration but to inhibit cell differentiation. With the use of pharmacological tools and FFA4-knockout mice, FFA4 was found to be responsible for ω-3 fatty acids-induced proliferation in vitro in club cells. Furthermore, accelerated recovery from naphthalene-induced airway injury in Omacor-treated mice was not observed in FFA4-knockout mice in vivo. Present findings indicate that ω-3 fatty acids-induced proliferation of bronchiole epithelial cells through FFA4 is responsible for Omacor-induced accelerated recovery from airway injury. Therefore, intermittent administration of Omacor needs to be tested for acute airway injury because ω-3 fatty acids stimulate proliferation but inhibit differentiation of club cells. Copyright © 2017 the American Physiological Society.

Characterization of the extracellular bactericidal factors of rat alveolar lining material.

PubMed Central

Coonrod, J D; Lester, R L; Hsu, L C

1984-01-01

The surfactant fraction (55,000-g pellet) of leukocyte-free rat bronchoalveolar lavage fluid contains factors that rapidly kill and lyse pneumococci. These factors were purified and identified biochemically by using a quantitative bactericidal test to monitor fractionation procedures. 91% of the antipneumococcal activity of rat surfactant was recovered in chloroform after extraction of rat surfactant with chloroform-methanol (Bligh-Dyer procedure). After chromatography on silicic acid with chloroform, acetone, and methanol, all detectable antibacterial activity (approximately 80% of the initial activity) eluted with the neutral lipids in chloroform. When rechromatographed on silicic acid with hexane, hexane-chloroform, and chloroform, the antibacterial activity eluted with FFA. Thin-layer chromatography (TLC) established that the antibacterial activity was confined to the FFA fraction. Gas-liquid chromatography showed that the fatty acid fraction contained a mixture of long-chain FFA (C12 to C22) of which 66.7% were saturated and 32.4% were unsaturated. The quantity of TLC-purified FFA needed to kill 50% of 10(8) pneumococci under standardized conditions (one bactericidal unit) was 10.6 +/- 0.5 micrograms. Purified FFA acted as detergents, causing release of [3H]choline from pneumococcal cell walls and increased bacterial cell membrane permeability, evidenced by rapid unloading of 3-O-[3H]methyl-D-glucose. FFA acting as detergents appear to account for the bactericidal and bacteriolytic activity of rat pulmonary surfactant for pneumococci. PMID:6548228

Frontal fibrosing alopecia treatment options.

PubMed

Fertig, Raymond; Tosti, Antonella

2016-11-01

Frontal fibrosing alopecia (FFA) is a rare dermatologic disease that causes scarring and hair loss and is increasing in prevalence worldwide. FFA patients typically present with hair loss in the frontal scalp region and eyebrows which may be associated with sensations of itching or burning. FFA is a clinically distinct variant of lichen planopilaris (LPP) that affects predominantly postmenopausal women, although men and premenopausal women may also be affected. Early diagnosis and prompt treatment are necessary to prevent definitive scarring and permanent hair loss. Data from retrospective studies indicate that 5-alpha-reductase inhibitors (5aRIs) are effective in stabilizing the disease. In our clinical experience, we have seen optimal results treating FFA patients with oral finasteride in conjunction with hydroxychloroquine, topical calcineurin inhibitors (tacrolimus) and excimer laser in patients with signs of active inflammation.

Dynamic Stability Parameters

DTIC Science & Technology

1981-05-01

2 € BBP a " Bm (t.) + Cn (;,)cos 0 sin 0 The analogous matches for the coefficients in Cn(t) may be obtained from Eq. (46) by replacing Cm. with Cni...but using only the moment equations of motion). 7.3 FFA , Stockholm Some of the free oscillation mechanisms used at FFA are shown in Fig. 25. In I...FIG. 28 FREE-SPIN HIGH ALPHA ROLL FIG. 29 STEADY-ROLL APPARATUS. FFA APPARATUS. AEDC-VKF. (REF. 27) 3-18 BALANCX WEIGHTS CALE 95-AY AND SUPPORT - SLIP

Pan evaporation prediction using a hybrid multilayer perceptron-firefly algorithm (MLP-FFA) model: case study in North Iran

NASA Astrophysics Data System (ADS)

Ghorbani, M. A.; Deo, Ravinesh C.; Yaseen, Zaher Mundher; H. Kashani, Mahsa; Mohammadi, Babak

2017-08-01

An accurate computational approach for the prediction of pan evaporation over daily time horizons is a useful decisive tool in sustainable agriculture and hydrological applications, particularly in designing the rural water resource systems, water use allocations, utilization and demand assessments, and the management of irrigation systems. In this study, a hybrid predictive model (Multilayer Perceptron-Firefly Algorithm (MLP-FFA)) based on the FFA optimizer that is embedded within the MLP technique is developed and evaluated for its suitability for the prediction of daily pan evaporation. To develop the hybrid MLP-FFA model, the pan evaporation data measured between 2012 and 2014 for two major meteorological stations (Talesh and Manjil) located at Northern Iran are employed to train and test the predictive model. The ability of the hybrid MLP-FFA model is compared with the traditional MLP and support vector machine (SVM) models. The results are evaluated using five performance criteria metrics: root mean square error (RMSE), mean absolute error (MAE), Nash-Sutcliffe efficiency (NS), and the Willmott's Index (WI). Taylor diagrams are also used to examine the similarity between the observed and predicted pan evaporation data in the test period. Results show that an optimal MLP-FFA model outperforms the MLP and SVM model for both tested stations. For Talesh, a value of WI = 0.926, NS = 0.791, and RMSE = 1.007 mm day-1 is obtained using MLP-FFA model, compared with 0.912, 0.713, and 1.181 mm day-1 (MLP) and 0.916, 0.726, and 1.153 mm day-1 (SVM), whereas for Manjil, a value of WI = 0.976, NS = 0.922, and 1.406 mm day-1 is attained that contrasts 0.972, 0.901, and 1.583 mm day-1 (MLP) and 0.971, 0.893, and 1.646 mm day-1 (SVM). The results demonstrate the importance of the Firefly Algorithm applied to improve the performance of the MLP-FFA model, as verified through its better predictive performance compared to the MLP and SVM model.

Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats.

PubMed

Kang, Hyun; Koppula, Sushruta

2015-03-01

Houttuynia cordata Thunb. (Saururaceae) is used traditionally in Asian countries to treat various disease symptoms. To study the effect of H. cordata ethyl acetate (HC-EA) extract on high-fat diet (HFD)-induced hepatic steatosis. HFD fed rats were orally dosed with HC-EA (100, 200, or 300 mg/kg) once daily for 8 weeks and the lipid profiles and protein expressions in hepatocytes were evaluated. HFD rats showed an increase (p < 0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), free fatty acids (FFAs), and reduced the high-density lipoprotein (HDL) levels. Treatment with HC-EA extract (300 mg/kg) restored the changes in plasma lipid levels of TC, TG, LDL, FFA, and HDL in HFD-fed rats by 34.8, 31.1, 51.4, 32.4, and 56.3%, respectively, compared with control rats (p < 0.01). HC-EA treatment also decreased the hepatic lipid accumulation (p < 0.001 at 300 mg/kg) and improved hepatic histological lesions. HC-EA extract enhanced AMPK phosphorylation and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated the gene expression of carnitine palmitoyl transferase-1 (CPT-1), and down-regulated sterol regulatory element binding protein 1, fatty acid synthase, and glutamate pyruvate transaminase protein levels in the livers of HFD-fed rats. Further, the increased expression of hepatic cytochrome P450 (CYP) composition such as CYP2E1 and CYP4A was also suppressed. Data suggest that HC-EA extract might act by regulating the AMPK-dependent pathway and related mediators and might be used in treating obesity-related liver diseases.

Theme: Teaching Agrimarketing.

ERIC Educational Resources Information Center

Leising, James; And Others

1993-01-01

Includes "Teaching Agrimarketing" (Leising); "Agrisales and Marketing" (Downey, McFarland); "Agrimarketing: A Tool Every Agriculture Student Needs" (Barrett); "Using FFA (Future Farmers of America) Activities to Teach Agrimarketing" (Egan); "FFA Commodity Marketing Activity" (Moore, Day); and…

Horticulture and the FFA

ERIC Educational Resources Information Center

Nelson, Clifford L.

1975-01-01

The article offers teachers of vocational horticulture a number of specific suggestions for organizing FFA horticulture chapters that will appeal to urban and suburban students and that will improve the quality of their learning. (AJ)

Comparison of free fatty acid content of human milk from Taiwanese mothers and infant formula.

PubMed

Chuang, Chih-Kuang; Yeung, Chun-Yan; Jim, Wai-Tim; Lin, Shuan-Pei; Wang, Tuen-Jen; Huang, Sung-Fa; Liu, Hsuan-Liang

2013-12-01

Few studies on the free fatty acid (FFA) content of milk from non-Caucasian mothers have been published. We compared the FFA concentrations in human milk (HM) from Taiwanese mothers of preterm (PTHM) and full-term infants (FTHM) and in infant formula (IF). Thirty-eight HM samples were collected from 23 healthy lactating mothers and 15 mothers who gave birth prematurely (range 29-35 weeks, mean 33 weeks). The regular formula and preterm infant formula (PTIF) for three brands of powdered IF were also evaluated. Milk samples were extracted and methylated for analysis by gas chromatography/mass spectrometry (GC/MS). Reference values for individual FFAs in breast milk from Taiwanese mothers were determined. The mean total FFAs were significantly higher in IF (21,554 μmol/L) and PTIF (19,836 μmol/L) than in FTHM (8,540 μmol/L) and PTHM (9,259 μmol/L) (p < 0.05). Saturated FAs were predominant in all types of milk (43.1% for FTHM, 42.8% for PTHM, 45.5% for IF and 45.3% for PTIF). Monounsaturated FAs were significantly higher in IF and PTIF (42.6% and 43.9%) than in FTHM and PTHM (37.7% and 39.5%), and polyunsaturated FAs in FTHM and PTHM (20% and 18.2%) were higher than in IF and PTIF (11.9% and 10.9%). HM had a more desirable linoleic acid/α-linolenic acid ratio than IF. No significant differences in individual FFAs in FTHM were observed among three lactating periods. FFA levels in HM from Taiwanese mothers are in agreement with results for different geographically distinct populations. Nevertheless, the FFA content in IF did not meet well with HM, particularly, the excess additives of saturated and monounsaturated FAs, and the shortage of polyunsaturated FAs. The effect of variations in FFA content in IF on future unfavorable outcomes such as obesity, atopic syndrome, and less optimal infant neurodevelopment should be further investigated. Copyright © 2013. Published by Elsevier B.V.

Experimental and clinical experience with iodine 123-labeled iodophenylpentadecanoic acid in cardiology.

PubMed

Reske, S N

1994-01-01

Iodine 123-labeled iodophenylpentadecanoic acid (IPPA) has been synthesized for investigating myocardial free fatty acid (FFA) metabolism. The diagnostic application of labeled FFA in heart disease may be important, because FFA is the preferred substrate of cardiac energy metabolism at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation, which is extremely sensitive to oxygen deprivation. This article outlines basic physiologic pathways of cardiac IPPA metabolism in normal, acutely ischemic, and reperfused viable myocardium and summarizes the results of experimental studies in animals, validating the application of IPPA as an 123I-labeled fatty acid analog. In addition, the most important clinical studies indicating the clinical use of IPPA for diagnosis of coronary heart disease and myocardial viability are presented.

Investigating the Influence of Polymers on Supersaturated Flufenamic Acid Cocrystal Solutions.

PubMed

Guo, Minshan; Wang, Ke; Hamill, Noel; Lorimer, Keith; Li, Mingzhong

2016-09-06

The development of enabling formulations is a key stage when demonstrating the effectiveness of pharmaceutical cocrystals to maximize the oral bioavailability for poorly water soluble drugs. Inhibition of drug crystallization from a supersaturated cocrystal solution through a fundamental understanding of the nucleation and crystal growth is important. In this study, the influence of the three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a copolymer of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the flufenamic acid (FFA) crystallization from three different supersaturated solutions of the pure FFA and two cocrystals of FFA-NIC CO and FFA-TP CO has been investigated by measuring nucleation induction times and desupersaturation rates in the presence and absence of seed crystals. It was found that the competition of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and coformer/polymer was a key factor responsible for maintaining supersaturation through nucleation inhibition and crystal growth modification in a cocrystal solution. The supersaturated cocrystal solutions with predissolved PEG demonstrated more effective stabilization in comparison to the pure FFA in the presence of the same polymer. In contrast, neither of the two cocrystal solutions, in the presence of PVP or PVP-VA, exhibited a better performance than the pure FFA with the same predissolved polymer. The study suggests that the selection of a polymeric excipient in a cocrystal formulation should not be solely dependent on the interplay of the parent drug and polymer without considering the coformer effects.

Prevalence of cystic macular lesions in patients with Usher II syndrome.

PubMed

Walia, S; Fishman, G A; Hajali, M

2009-05-01

To evaluate the prevalence of cystic macular lesions in patients with Usher II syndrome. All Usher type II patients seen in the inherited eye disease clinic at the University of Illinois at Chicago between January 2002 and December 2007 were included (n=76). Each participating patient underwent a detailed clinical examination, including best-corrected visual acuity, slit-lamp biomicroscopy and dilated fundus examination. The presence of cystoid lesions was determined by optical coherence tomography (OCT), fundus fluorescein angiogram (FFA), fundus photographs and/or clinical examination. A cystic-appearing macular change was observed in at least one eye in 19 out of the 76 patients (25%), 13 on the basis of OCT, five using FFA (two solely with the use of FFA and three based on clinical notes and FFA findings) and one based solely on clinical notes. Of the 18 patients with CME, determined by OCT or FFA, five (27.8%) showed either a funduscopically normal-appearing macula (n=4) or an atrophic appearing macular change (n=1). One-fourth of our total cohort of Usher II patients had cystic macular lesions. Moreover, a funduscopically normal-appearing macula was observed in 22% (n=4) of our 18 patients with cystic-appearing macular lesions on OCT and/or FFA testing. On the basis of the reasonably high prevalence of cystic macular lesions in our cohort, it would seem prudent to evaluate Usher II patients for the presence of cystoid macular oedema.

An investigation of pulsar searching techniques with the fast folding algorithm

NASA Astrophysics Data System (ADS)

Cameron, A. D.; Barr, E. D.; Champion, D. J.; Kramer, M.; Zhu, W. W.

2017-06-01

Here, we present an in-depth study of the behaviour of the fast folding algorithm (FFA), an alternative pulsar searching technique to the fast Fourier transform (FFT). Weaknesses in the FFT, including a susceptibility to red noise, leave it insensitive to pulsars with long rotational periods (P > 1 s). This sensitivity gap has the potential to bias our understanding of the period distribution of the pulsar population. The FFA, a time-domain based pulsar searching technique, has the potential to overcome some of these biases. Modern distributed-computing frameworks now allow for the application of this algorithm to all-sky blind pulsar surveys for the first time. However, many aspects of the behaviour of this search technique remain poorly understood, including its responsiveness to variations in pulse shape and the presence of red noise. Using a custom CPU-based implementation of the FFA, ffancy, we have conducted an in-depth study into the behaviour of the FFA in both an ideal, white noise regime as well as a trial on observational data from the High Time Resolution Universe South Low Latitude pulsar survey, including a comparison to the behaviour of the FFT. We are able to both confirm and expand upon earlier studies that demonstrate the ability of the FFA to outperform the FFT under ideal white noise conditions, and demonstrate a significant improvement in sensitivity to long-period pulsars in real observational data through the use of the FFA.

Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells.

PubMed

Rodríguez-Enríquez, Sara; Hernández-Esquivel, Luz; Marín-Hernández, Alvaro; El Hafidi, Mohammed; Gallardo-Pérez, Juan Carlos; Hernández-Reséndiz, Ileana; Rodríguez-Zavala, José S; Pacheco-Velázquez, Silvia C; Moreno-Sánchez, Rafael

2015-08-01

Oxidative phosphorylation (OxPhos) is functional and sustains tumor proliferation in several cancer cell types. To establish whether mitochondrial β-oxidation of free fatty acids (FFAs) contributes to cancer OxPhos functioning, its protein contents and enzyme activities, as well as respiratory rates and electrical membrane potential (ΔΨm) driven by FFA oxidation were assessed in rat AS-30D hepatoma and liver (RLM) mitochondria. Higher protein contents (1.4-3 times) of β-oxidation (CPT1, SCAD) as well as proteins and enzyme activities (1.7-13-times) of Krebs cycle (KC: ICD, 2OGDH, PDH, ME, GA), and respiratory chain (RC: COX) were determined in hepatoma mitochondria vs. RLM. Although increased cholesterol content (9-times vs. RLM) was determined in the hepatoma mitochondrial membranes, FFAs and other NAD-linked substrates were oxidized faster (1.6-6.6 times) by hepatoma mitochondria than RLM, maintaining similar ΔΨm values. The contents of β-oxidation, KC and RC enzymes were also assessed in cells. The mitochondrial enzyme levels in human cervix cancer HeLa and AS-30D cells were higher than those observed in rat hepatocytes whereas in human breast cancer biopsies, CPT1 and SCAD contents were lower than in human breast normal tissue. The presence of CPT1 and SCAD in AS-30D mitochondria and HeLa cells correlated with an active FFA utilization in HeLa cells. Furthermore, the β-oxidation inhibitor perhexiline blocked FFA utilization, OxPhos and proliferation in HeLa and other cancer cells. In conclusion, functional mitochondria supported by FFA β-oxidation are essential for the accelerated cancer cell proliferation and hence anti-β-oxidation therapeutics appears as an alternative promising approach to deter malignant tumor growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implicit Race Bias Decreases the Similarity of Neural Representations of Black and White Faces

PubMed Central

Brosch, Tobias; Bar-David, Eyal; Phelps, Elizabeth A.

2013-01-01

Implicit race bias has been shown to affect decisions and behaviors. It may also change perceptual experience by increasing perceived differences between social groups. We investigated how this phenomenon may be expressed at the neural level by testing whether the distributed blood-oxygenation-level-dependent (BOLD) patterns representing Black and White faces are more dissimilar in participants with higher implicit race bias. We used multivoxel pattern analysis to predict the race of faces participants were viewing. We successfully predicted the race of the faces on the basis of BOLD activation patterns in early occipital visual cortex, occipital face area, and fusiform face area (FFA). Whereas BOLD activation patterns in early visual regions, likely reflecting different perceptual features, allowed successful prediction for all participants, successful prediction on the basis of BOLD activation patterns in FFA, a high-level face-processing region, was restricted to participants with high pro-White bias. These findings suggest that stronger implicit pro-White bias decreases the similarity of neural representations of Black and White faces. PMID:23300228

Diurnal variations in blood gases and metabolites for draught Zebu and Simmental oxen.

PubMed

Zanzinger, J; Hoffmann, I; Becker, K

1994-01-01

In previous articles it has been shown that blood parameters may be useful to assess physical fitness in draught cattle. The aim of the present study was to detect possible variations in baseline values for the key metabolites: lactate and free fatty acids (FFA), and for blood gases in samples drawn from a catheterized jugular vein. Sampling took place immediately after venipuncture at intervals of 3 min for 1 hr in Simmental oxen (N = 6) and during a period of 24 hr at intervals of 60 min for Zebu (N = 4) and Simmental (N = 6) oxen. After puncture of the vein, plasma FFA and oxygen (pvO2) were elevated for approximately 15 min. All parameters returned to baseline values within 1 hr of the catheter being inserted. Twenty-four-hour mean baseline values for all measured parameters were significantly different (P < or = 0.001) between Zebu and Simmental. All parameters elicited diurnal variations which were mainly related to feed intake. The magnitude of these variations is comparable to the responses to light draught work. It is concluded that a strict standardization of blood sampling, at least in respect of time after feeding, is required for a reliable interpretation of endurance-indicating blood parameters measured under field conditions.

Structure, enzymatic transformation, anticancer activity of fucoidan and sulphated fucooligosaccharides from Sargassum horneri.

PubMed

Silchenko, Artem S; Rasin, Anton B; Kusaykin, Mikhail I; Kalinovsky, Anatoly I; Miansong, Zhang; Changheng, Liu; Malyarenko, Olesya; Zueva, Anastasiya O; Zvyagintseva, Tatyana N; Ermakova, Svetlana P

2017-11-01

Structure and anticancer activity of fucoidan from Sargassum horneri and from products of its enzymatic transformation were investigated. A gene that encodes fucoidanase ffa1 in the marine bacteria F. algae was identified, cloned and the protein (FFA1) was produced in Escherichia coli. The mass of the gene product FFA1 is 111kDa. Sequence analysis has revealed that fucoidanase FFA1 belongs to the GH107 (CAZy) family. Recombinant fucoidanase FFA1 was used to produce fucooligosaccharides. Structure of 5 sulphated oligosaccharides with polymerization degree 4-10 was established by NMR-spectroscopy. The fucoidan extracted from S. horneri is almost pure fucan. The main chain of the fucoidan is established to consist mostly of the repeating →3-α-l-Fucp(2SO 3 - )-1→4-α-l-Fucp(2,3SO 3 - )-1→ fragment, with insertions of →3-α-l-Fucp(2,4SO 3 - )-1→ fragment. Unsulphated side chains with the α-l-Fucp-1→2-α-l-Fucp-1→ structure connect to the main one at the C4 of monosaccharide residue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Meeting record for FFA working meeting of November 15, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stejskal, G.F.

1992-01-03

This document provides a meeting record of the Federal Facility Agreement (FFA) working meeting to discuss progress on old issues and further required actions regarding environmental impacts of the Savannah River Facility. (FI)

Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study.

PubMed

Sachse, Benjamin; Meinl, Walter; Sommer, Yasmin; Glatt, Hansruedi; Seidel, Albrecht; Monien, Bernhard H

2016-01-01

5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent rodent carcinogens that are present in thermally processed foodstuffs. The carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)-mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous SULT forms substantially differ in substrate specificity and tissue distribution. This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and rats. The catalytic efficiencies (k cat/K M) of HMF sulfoconjugation of human SULT1A1 (13.7 s(-1) M(-1)), mouse Sult1a1 (15.8 s(-1) M(-1)) and 1d1 (4.8 s(-1) M(-1)) and rat Sult1a1 (5.3 s(-1) M(-1)) were considerably higher than those of all other SULT forms investigated (≤0.73 s(-1 )M(-1)). FFA sulfoconjugation was monitored using adenosine as a nucleophilic scavenger for the reactive 2-sulfoxymethylfuran (t 1/2 = 20 s at 37 °C). The resulting adduct N (6)-((furan-2-yl)methyl)-adenosine (N (6)-MF-A) was quantified by isotope-dilution UPLC-MS/MS. The rates of N (6)-MF-A formation showed that hSULT1A1 and its orthologues in mice and rats were also the most important contributors to FFA sulfoconjugation in each of the species. Taken together, the catalytic capacity of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which carcinogenic effects of HMF and FFA were detected. This is of primary concern due to the expression of hSULT1A1 in many different tissues.

Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography.

PubMed

Kendziorra, Kai; Wolf, Henrike; Meyer, Philipp Mael; Barthel, Henryk; Hesse, Swen; Becker, Georg Alexander; Luthardt, Julia; Schildan, Andreas; Patt, Marianne; Sorger, Dietlind; Seese, Anita; Gertz, Herman-Josef; Sabri, Osama

2011-03-01

Postmortem studies indicate a loss of nicotinic acetylcholine receptor (nAChRs) in Alzheimer's disease (AD). In order to establish whether these changes in the cholinergic system occur at an early stage of AD, we carried out positron emission tomography (PET) with a specific radioligand for the α4β2* nicotinic acetylcholine receptor (α4β2* nAChR) in patients with mild to moderate AD and in patients with amnestic mild cognitive impairment (MCI), who have a high risk to progress to AD. Nine patients with moderate AD, eight patients with MCI and seven age-matched healthy controls underwent 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BP(ND)) of 2-[(18)F]FA-85380 was calculated using either the corpus callosum or the cerebellum as reference regions. PET data were analysed by region of interest analysis and by voxel-based analysis. Both patients with AD and MCI showed a significant reduction in 2-[(18)F]FA-85380 BP(ND) in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[(18)F]FA-85380 BP(ND) correlated with the severity of cognitive impairment. Only MCI patients that converted to AD in the later course (n = 5) had a reduction in 2-[(18)F]FA-85380 BP(ND). 2-[(18)F]FA-85380 PET appears to be a sensitive and feasible tool for the detection of a reduction in α4β2* nAChRs which seems to be an early event in AD. In addition, 2-[(18)F]FA-85380 PET might give prognostic information about a conversion from MCI to AD.

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation.

PubMed

Jocken, J W E; Blaak, E E; Schiffelers, S; Arner, P; van Baak, M A; Saris, W H M

2007-05-01

Obesity is associated with a blunted beta-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the beta (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein beta (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation. Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m(2)) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective beta-agonist isoprenaline (ISO). In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation. These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo beta-adrenoceptor-mediated lipolysis and fat oxidation during beta-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.

Free fatty acid effects on myokine production in combination with exercise mimetics.

PubMed

Sánchez, Juana; Nozhenko, Yuriy; Palou, Andreu; Rodríguez, Ana M

2013-08-01

We aimed to study the effects of free fatty acids (FFAs) alone and combined with the exercise mimetics adrenaline and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in the production of IL6, IL15 and Irisin in muscle cells, using a time-sequential model. Differentiated C2C12 myotubes were treated with FFA, adrenaline or AICAR alone for 0, 1, 3, 8, 12 and 24 h and with double or triple combinations for 0, 3 and 24 h. Levels of mRNA in cells and protein in the medium were measured. Adrenaline, AICAR and FFA showed no significant effects on Irisin expression, while the presence in the culture of adrenaline and/or AICAR decreased IL15 mRNA expression. On contrary, the three signals showed a deep, rapid impact on the IL6 induction, especially when both AICAR and FFA were present. The different response in IL6 versus IL15 regulation may be explained by their different energy-activating versus muscle-cell-hypertrophy suggested roles, considering that adrenaline and AMPK are involved in the activation of energy-generating pathways. Moreover, the results suggest FFAs are components that may regulate IL6 production and may have a role in muscle-adipose tissue crosstalk. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimising the operational parameters of a spherical steriliser for the treatment of oil palm fresh fruit bunch

NASA Astrophysics Data System (ADS)

Kumaradevan, D.; Chuah, K. H.; Moey, L. K.; Mohan, V.; Wan, W. T.

2015-09-01

The extraction of crude palm oil (CPO) begins with the sterilization of oil palm fresh fruit bunch (FFB) in a pressurized, saturated-steam chamber. Sterilization loosens the palm fruits from the stalks and deactivates the free fatty acid (FFA)-producing enzymes. Operational parameters affecting the quality and yield of CPO from an industrial spherical sterilizer are studied at a palm oil mill. The factors are the ripeness of FFB, the number of days before treatment of FFB, and the number of pressure peaks applied in the sterilization process. The results indicate that the degree of ripeness of FFB is the most important parameter affecting the quality and yield of CPO. Ripeness is graded based on the fruits’ colour and the presence of loose fruits. Over ripe FFB that goes for the sterilization process has higher FFA content in CPO and more oil loss to the condensate chamber. The spontaneous reaction on FFB due to accumulation at the loading ramp also gives rise to higher FFA content. Oil loss to condensate chamber is reduced using a two-peak sterilization technique for over ripe FFB; the peak refers to the pressure level of stream after a flushing and refilling cycle. Overall, the generated solution improves the quality and yield of the palm oil mill.

Ferric sulphate catalysed esterification of free fatty acids in waste cooking oil.

PubMed

Gan, Suyin; Ng, Hoon Kiat; Ooi, Chun Weng; Motala, Nafisa Osman; Ismail, Mohd Anas Farhan

2010-10-01

In this work, the esterification of free fatty acids (FFA) in waste cooking oil catalysed by ferric sulphate was studied as a pre-treatment step for biodiesel production. The effects of reaction time, methanol to oil ratio, catalyst concentration and temperature on the conversion of FFA were investigated on a laboratory scale. The results showed that the conversion of FFA reached equilibrium after an hour, and was positively dependent on the methanol to oil molar ratio and temperature. An optimum catalyst concentration of 2 wt.% gave maximum FFA conversion of 59.2%. For catalyst loadings of 2 wt.% and below, this catalysed esterification was proposed to follow a pseudo-homogeneous pathway akin to mineral acid-catalysed esterification, driven by the H(+) ions produced through the hydrolysis of metal complex [Fe(H(2)O)(6)](3+) (aq). Copyright 2010 Elsevier Ltd. All rights reserved.

Processing of configural and componential information in face-selective cortical areas.

PubMed

Zhao, Mintao; Cheung, Sing-Hang; Wong, Alan C-N; Rhodes, Gillian; Chan, Erich K S; Chan, Winnie W L; Hayward, William G

2014-01-01

We investigated how face-selective cortical areas process configural and componential face information and how race of faces may influence these processes. Participants saw blurred (preserving configural information), scrambled (preserving componential information), and whole faces during fMRI scan, and performed a post-scan face recognition task using blurred or scrambled faces. The fusiform face area (FFA) showed stronger activation to blurred than to scrambled faces, and equivalent responses to blurred and whole faces. The occipital face area (OFA) showed stronger activation to whole than to blurred faces, which elicited similar responses to scrambled faces. Therefore, the FFA may be more tuned to process configural than componential information, whereas the OFA similarly participates in perception of both. Differences in recognizing own- and other-race blurred faces were correlated with differences in FFA activation to those faces, suggesting that configural processing within the FFA may underlie the other-race effect in face recognition.

Adsorption of Free Fatty Acid (FFA) in Low-Grade Cooking Oil Used Activated Natural Zeolite as Adsorbent

NASA Astrophysics Data System (ADS)

Larasati Tres Ayu Putranti, Monika; Kompiang Wirawan, Sang; Made Bendiyasa, I.

2018-01-01

Adsorption of free fatty acid (FFA) in low-grade cooking oil using active natural zeolite adsorbent was done as an effort to improve the quality of low-grade cooking oil so that it can fulfill the standard of fried oil which has been set on SNI 01-3741-2013. Adsorption was carried out with natural zeolite which activated with HCl and NaOH solution followed by the calcination process. The results showed that the NaOH activated zeolite decreased FFA content in low-grade cooking oil more than the HCl activated natural zeolite, with optimum NaOH concentration was 0.75 M. In the adsorption equilibrium analysis with temperature variation (25 °C, 40 °C, 80 °C ), obtained that adsorption of FFA with NaOH activated natural zeolite follows Adsorption Isotherm Freundlich Model with equilibrium constant value was 20,5873; 0,9629 dan 0,8053.

Neural Decoding Reveals Impaired Face Configural Processing in the Right Fusiform Face Area of Individuals with Developmental Prosopagnosia

PubMed Central

Zhang, Jiedong; Liu, Jia

2015-01-01

Most of human daily social interactions rely on the ability to successfully recognize faces. Yet ∼2% of the human population suffers from face blindness without any acquired brain damage [this is also known as developmental prosopagnosia (DP) or congenital prosopagnosia]). Despite the presence of severe behavioral face recognition deficits, surprisingly, a majority of DP individuals exhibit normal face selectivity in the right fusiform face area (FFA), a key brain region involved in face configural processing. This finding, together with evidence showing impairments downstream from the right FFA in DP individuals, has led some to argue that perhaps the right FFA is largely intact in DP individuals. Using fMRI multivoxel pattern analysis, here we report the discovery of a neural impairment in the right FFA of DP individuals that may play a critical role in mediating their face-processing deficits. In seven individuals with DP, we discovered that, despite the right FFA's preference for faces and it showing decoding for the different face parts, it exhibited impaired face configural decoding and did not contain distinct neural response patterns for the intact and the scrambled face configurations. This abnormality was not present throughout the ventral visual cortex, as normal neural decoding was found in an adjacent object-processing region. To our knowledge, this is the first direct neural evidence showing impaired face configural processing in the right FFA in individuals with DP. The discovery of this neural impairment provides a new clue to our understanding of the neural basis of DP. PMID:25632131

Study of UltraHigh Performance Supercritical Fluid Chromatography to measure free fatty acids with out fatty acid ester preparation.

PubMed

Ashraf-Khorassani, M; Isaac, G; Rainville, P; Fountain, K; Taylor, L T

2015-08-01

Most lipids are best characterized by their fatty acids which may differ in (a) chain length, (b) degree of unsaturation, (c) configuration and position of the double bonds, and (d) the presence of other functionalities. Thus, a fast, simple, and quantitative analytical technique to determine naturally occurring free fatty acids (FFA) in different samples is very important. Just as for saponified acylglycerols, the determination of FFA's has generally been carried out by high resolution gas chromatography (HRGC). The use of an open tubular capillary column coupled with a flame ionization or mass spectrometric detector provides for both high resolution and quantification of FFA's but only after conversion of all free fatty acids to fatty acid methyl esters (FAME) or pentafluorobenzyl esters. Unfortunately, volatilization of labile ester derivatives of mono- and poly-unsaturated FFA's can cause both thermal degradation and isomerization of the fatty acid during HRGC. The employment of a second generation instrument (here referred to as UltraHigh Performance Supercritical Fluid Chromatograph, UHPSFC) with high precision for modified flow and repeated back pressure adjustment in conjunction with sub-2μm various bonded silica particles (coupled with evaporative light scattering, ELSD, and mass spectrometric, MS, detection) for separation and detection of the following mixtures is described: (a) 31 free fatty acids, (b) isomeric FFA's, and (c) lipophilic materials in two real world fish oil samples. Limits of detection for FFA's via UHPSFC/MS and UHPSFC/ELSD versus detection of FAME's via HRGC/MS are quantitatively compared. Copyright © 2015 Elsevier B.V. All rights reserved.

Expectation and Surprise Determine Neural Population Responses in the Ventral Visual Stream

PubMed Central

Egner, Tobias; Monti, Jim M.; Summerfield, Christopher

2014-01-01

Visual cortex is traditionally viewed as a hierarchy of neural feature detectors, with neural population responses being driven by bottom-up stimulus features. Conversely, “predictive coding” models propose that each stage of the visual hierarchy harbors two computationally distinct classes of processing unit: representational units that encode the conditional probability of a stimulus and provide predictions to the next lower level; and error units that encode the mismatch between predictions and bottom-up evidence, and forward prediction error to the next higher level. Predictive coding therefore suggests that neural population responses in category-selective visual regions, like the fusiform face area (FFA), reflect a summation of activity related to prediction (“face expectation”) and prediction error (“face surprise”), rather than a homogenous feature detection response. We tested the rival hypotheses of the feature detection and predictive coding models by collecting functional magnetic resonance imaging data from the FFA while independently varying both stimulus features (faces vs houses) and subjects’ perceptual expectations regarding those features (low vs medium vs high face expectation). The effects of stimulus and expectation factors interacted, whereby FFA activity elicited by face and house stimuli was indistinguishable under high face expectation and maximally differentiated under low face expectation. Using computational modeling, we show that these data can be explained by predictive coding but not by feature detection models, even when the latter are augmented with attentional mechanisms. Thus, population responses in the ventral visual stream appear to be determined by feature expectation and surprise rather than by stimulus features per se. PMID:21147999

Biodiesel production from vegetable oil and waste animal fats in a pilot plant.

PubMed

Alptekin, Ertan; Canakci, Mustafa; Sanli, Huseyin

2014-11-01

In this study, corn oil as vegetable oil, chicken fat and fleshing oil as animal fats were used to produce methyl ester in a biodiesel pilot plant. The FFA level of the corn oil was below 1% while those of animal fats were too high to produce biodiesel via base catalyst. Therefore, it was needed to perform pretreatment reaction for the animal fats. For this aim, sulfuric acid was used as catalyst and methanol was used as alcohol in the pretreatment reactions. After reducing the FFA level of the animal fats to less than 1%, the transesterification reaction was completed with alkaline catalyst. Due to low FFA content of corn oil, it was directly subjected to transesterification. Potassium hydroxide was used as catalyst and methanol was used as alcohol for transesterification reactions. The fuel properties of methyl esters produced in the biodiesel pilot plant were characterized and compared to EN 14214 and ASTM D6751 biodiesel standards. According to the results, ester yield values of animal fat methyl esters were slightly lower than that of the corn oil methyl ester (COME). The production cost of COME was higher than those of animal fat methyl esters due to being high cost biodiesel feedstock. The fuel properties of produced methyl esters were close to each other. Especially, the sulfur content and cold flow properties of the COME were lower than those of animal fat methyl esters. The measured fuel properties of all produced methyl esters met ASTM D6751 (S500) biodiesel fuel standards. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hazard Assessment Computer System HACS/UIM Users’ Operation Manual. Volume II.

DTIC Science & Technology

1981-09-01

AMMONIUM OXALATE FAS FERROUS AMMONIUM SULFATE FCL FERRIC CHLORIDE FCP FERRIC GLYCEROPHOSPHATE FEC FERROUS CHLORIDE FFA FURFURAL FFB FERROUS FLUOROBORATE...FAL FFA FFBi FMA FNS FSA FSL FXX BAK GAT SAY SCM GCR GCS SOC SOS SPL SRF GSR STA J-2 HAC HAI HAL HEIR HCC HCL HCN HDC HE’S HDZ HFA HFX HMD HMI HPA...ENP EOEI EOP EOT EPC ETA ETC ETD ETf3 ETI FAL FFA FFB FMA FMS VSL OCR GOS GIA MAC HAI HCL Ht’Z HFA HMD HMI HPA HPdkt HPO HSS HXG IAA IAC IAL IAN IBR

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles.

PubMed

Lara, Giovanna Gomes; Cipreste, Marcelo Fernandes; Andrade, Gracielle Ferreira; Silva, Wellington Marcos da; Sousa, Edésia Martins Barros de

2018-01-09

Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium-iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones.

Functional organization of the face-sensitive areas in human occipital-temporal cortex.

PubMed

Shao, Hanyu; Weng, Xuchu; He, Sheng

2017-08-15

Human occipital-temporal cortex features several areas sensitive to faces, presumably forming the biological substrate for face perception. To date, there are piecemeal insights regarding the functional organization of these regions. They have come, however, from studies that are far from homogeneous with regard to the regions involved, the experimental design, and the data analysis approach. In order to provide an overall view of the functional organization of the face-sensitive areas, it is necessary to conduct a comprehensive study that taps into the pivotal functional properties of all the face-sensitive areas, within the context of the same experimental design, and uses multiple data analysis approaches. In this study, we identified the most robustly activated face-sensitive areas in bilateral occipital-temporal cortices (i.e., AFP, aFFA, pFFA, OFA, pcSTS, pSTS) and systemically compared their regionally averaged activation and multivoxel activation patterns to 96 images from 16 object categories, including faces and non-faces. This condition-rich and single-image analysis approach critically samples the functional properties of a brain region, allowing us to test how two basic functional properties, namely face-category selectivity and face-exemplar sensitivity are distributed among these regions. Moreover, by examining the correlational structure of neural responses to the 96 images, we characterize their interactions in the greater face-processing network. We found that (1) r-pFFA showed the highest face-category selectivity, followed by l-pFFA, bilateral aFFA and OFA, and then bilateral pcSTS. In contrast, bilateral AFP and pSTS showed low face-category selectivity; (2) l-aFFA, l-pcSTS and bilateral AFP showed evidence of face-exemplar sensitivity; (3) r-OFA showed high overall response similarities with bilateral LOC and r-pFFA, suggesting it might be a transitional stage between general and face-selective information processing; (4) r-aFFA showed high face-selective response similarity with r-pFFA and r-OFA, indicating it was specifically involved in processing face information. Results also reveal two properties of these face sensitive regions across the two hemispheres: (1) the averaged left intra-hemispheric response similarity for the images was lower than the averaged right intra-hemispheric and the inter-hemispheric response similarity, implying convergence of face processing towards the right hemisphere, and (2) the response similarities between homologous regions in the two hemispheres decreased as information processing proceeded from the early, more posterior, processing stage (OFA), indicating an increasing degree of hemispheric specialization and right hemisphere bias for face information processing. This study contributes to an emerging picture of how faces are processed within the occipital and temporal cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

Salubrious effect of Kalpaamruthaa, a modified indigenous preparation in adjuvant-induced arthritis in rats--a biochemical approach.

PubMed

Mythilypriya, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanadam

2008-05-28

Interactions between the phytochemicals and drugs and their combinations are capable of providing longer remissions and perhaps a complete cure for many diseases including rheumatoid arthritis (RA). In addition to articular manifestations in RA, extra-articular signs involving reticuloendothelial and hepatic systems are an indication of more severe disease and thus, have prognostic value. The present study was designed to illustrate the beneficial outcome of the drug Kalpaamruthaa (constituting Semecarpus anacardium nut milk extract, fresh dried powder of Emblica officinalis fruit and honey) in adjuvant-induced arthritic rat model with respect to the changes in extra-articular manifestation involving hematological and cellular constituents. Levels of hematological parameters, cellular constituents, activities of marker enzymes and the level of DNA damage were assessed in control, arthritis-induced, SA, KA and drug control treated rats. Significant decrease (p<0.005) in the levels of Hb, RBC, PCV, total protein, albumin, A/G ratio, plasma uric acid, urinary urea, uric acid, creatinine, FFA, HDL and significant increase (p<0.05) in the levels of WBC, platelet count, ESR, globulin, plasma creatinine, blood glucose, urea, AST, ALT, ALP, TC, FC, TG, PL, LDL and VLDL were observed in arthritic rats. No other significant change was observed in tissue DNA and RNA levels of control and experimental animals. On the contrary an increase in DNA damage was observed in arthritic rats when compared to control animals. The above said derangements were brought back to near normal levels upon SA and KA treatments and KA revealed a profound beneficial effect than SA. The enhanced effect of KA might be attributed to the combined effects of phytoconstituents such as flavonoids, tannins and other compounds such as vitamin C present in KA. Thus KA via this preliminary protective effect might contribute to the amelioration of the disease process.

Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.

PubMed

Yang, Weichun; Shi, He; Zhang, Jianfen; Shen, Ziyi; Zhou, Guangyu; Hu, Minyu

2017-01-31

The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P < 0.05) and the expression of IL-1, TNF-α and GFAP in the brains had increased (P < 0.05). In the second week, the expression of FFA and APP in the brains, and the amount of apoptotic neurons, had increased (P < 0.05). In the third week, the levels of VEGF, Ox-LDL and Aβ had increased, and the expression of Claudin-5 had decreased in the brains (P < 0.05). In the fourth week, the levels of TC, LDL-C and the amount of apoptotic neurons had increased (P < 0.05). The correlation analysis showed a positive correlation among FFA, TNF-α, VEGF, ox-LDL, Aβ, GFAP and neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P < 0.05). Hyperlipidemia may activate astrocytes by means of high levels of TG that will have direct toxic effects on the cerebral vessels and neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight junction protein Claudin-5 and change the permeability of blood-brain barriers to factors that could damage cerebral vessels and neurons.

Transport of 13C-oleate in adipocytes measured using multi imaging mass spectrometry.

PubMed

Kleinfeld, Alan M; Kampf, J Patrick; Lechene, Claude

2004-11-01

The mechanism of long chain free fatty acid (FFA) transport across cell membranes is under active investigation. Here we describe the use of multi imaging mass spectrometry (MIMS) to monitor intracellular concentrations of FFA and provide new insight into FFA transport in cultured adipocytes. Cells were incubated with 13C-oleate:BSA and either dried directly or dried after washing with a medium deprived of 13C-oleate:BSA. Cells were analyzed with MIMS using a scanning primary Cs+ ion beam and 12C-, 13C-, 12C14N-, 13C14N-) (or 12C 15N-) were imaged simultaneously. From these quantitative images the values of the 13C/ 12C ratios were determined in the intracellular lipid droplets, in the cytoplasm and outside the 3T3F442A adipocytes. The results indicate that after incubation with 13C-oleate:BSA the droplet 13C/ 12C ratio was 15 +/- 6%. This value is about 14-fold higher than the 13C/ 12C terrestrial ratio (1.12%). After washing the 13C-oleate:BSA, the droplet 13C/ 12C ratios decreased to 1.6 +/- 0.1%, about 40% greater than the natural abundance. Results for washed cells indicate that relatively little FFA was esterified. The unwashed cell results, together with the value of the lipid water partition coefficient, reveal that intracellular unbound FFA (FFAu) concentrations were on average about 4.5-fold greater than the extracellular FFAu concentrations. These results are consistent with the possibility that FFA may be pumped into adipocytes against their electro-chemical potential. This work demonstrates that MIMS can be used to image and quantitate stable isotope labeled fatty acid in intracellular lipid droplets.

Detection of retinal capillary nonperfusion in fundus fluorescein angiogram of diabetic retinopathy.

PubMed

Rasta, Seyed Hossein; Nikfarjam, Shima; Javadzadeh, Alireza

2015-01-01

Retinal capillary nonperfusion (CNP) is one of the retinal vascular diseases in diabetic retinopathy (DR) patients. As there is no comprehensive detection technique to recognize CNP areas, we proposed a different method for computing detection of ischemic retina, non-perfused (NP) regions, in fundus fluorescein angiogram (FFA) images. Whilst major vessels appear as ridges, non-perfused areas are usually observed as ponds that are surrounded by healthy capillaries in FFA images. A new technique using homomorphic filtering to correct light illumination and detect the ponds surrounded in healthy capillaries on FFA images was designed and applied on DR fundus images. These images were acquired from the diabetic patients who had referred to the Nikookari hospital and were diagnosed for diabetic retinopathy during one year. Our strategy was screening the whole image with a fixed window size, which is small enough to enclose areas with identified topographic characteristics. To discard false nominees, we also performed a thresholding operation on the screen and marked images. To validate its performance we applied our detection algorithm on 41 FFA diabetic retinopathy fundus images in which the CNP areas were manually delineated by three clinical experts. Lesions were found as smooth regions with very high uniformity, low entropy, and small intensity variations in FFA images. The results of automated detection method were compared with manually marked CNP areas so achieved sensitivity of 81%, specificity of 78%, and accuracy of 91%.The result was present as a Receiver operating character (ROC) curve, which has an area under the curve (AUC) of 0.796 with 95% confidence intervals. This technique introduced a new automated detection algorithm to recognize non-perfusion lesions on FFA. This has potential to assist detecting and managing of ischemic retina and may be incorporated into automated grading diabetic retinopathy structures.

[Fundus fluorescein angiography in metastatic choroidal carcinomas and differentiating metastatic choroidal carcinomas from primary choroidal melanomas].

PubMed

Li, Lei; Wang, Wen-Ji; Chen, Rong-Jia; Qian, Jiang; Luo, Chuan-Qi; Zhang, Yong-Jin; Shen, Ying; Ye, Xiao-Feng; Gao, Qiao-Yun

2011-01-01

To investigate the characteristics of fundus fluorescein angiography (FFA) in metastatic choroidal carcinomas and determine the value of FFA in differentiating metastatic choroidal carcinomas from primary choroidal melanomas. It was a retrospective case series. The retrospective analysis of clinical data and FFA findings was performed in 23 eyes of 22 patients with metastatic choroidal carcinomas and 31 eyes of 31 patients with primary choroidal melanomas as the control. Ocular fundus findings of metastatic choroidal carcinomas were divided into three types: solitary flat (tumor thickness less than 3 mm), solitary elevated (tumor thickness more than 3 mm) or diffuse type. FFA of the three types showed hypofluorescence during the arterial phase and progressive hyperfluorescence during the subsequent phases. The border of the lesions revealed retinal capillary dilation during the arteriovenous phase and persistent pinpoint leakage throughout the angiogram. Retinal capillary dilation and pinpoint leakage were more frequently presented in the solitary flat type. Simultaneous visualization of retinal and tumor circulation (the so called double circulation) was more frequently presented in the solitary elevated type. Pinpoint leakage could be detected in 17 (73.91%) eyes of metastatic choroidal carcinomas and in 5 (16.13%) eyes of primary choroidal melanomas. The difference between the visibility of pinpoint leakage in metastatic choroidal carcinomas and primary choroidal melanomas was statistically significant (P = 0.0000). When pinpoint leakage of FFA was used to differentiate metastatic choroidal carcinomas from primary choroidal melanomas, the sensitivity, specificity, accuracy, positive and negative predictive values were 73.91%, 83.87%, 79.63%, 77.27%, 81.25% respectively. FFA is helpful for the diagnosis of metastatic choroidal carcinomas. Pinpoint leakage on the border of lesions has some value in differentiating metastatic choroidal carcinomas from primary choroidal melanomas.

Potentially conflicting metabolic demands of diving and exercise in seals.

PubMed

Castellini, M A; Murphy, B J; Fedak, M; Ronald, K; Gofton, N; Hochachka, P W

1985-02-01

Metabolic replacement rates (Ra) for glucose and free fatty acids (FFA) were determined during rest, exercise, and diving conditions in the gray seal using bolus injections of radiotracers. In the exercise experiments the seal swam at a metabolic rate elevated twofold over resting Ra for glucose and FFA while resting were similar to values found in terrestrial mammals and other marine mammal species. During exercise periods glucose turnover increased slightly while FFA turnover changes were variable. However, the energetic demands of exercise could not be met by the increase in the replacement rates of glucose or FFA even if both were completely oxidized. Under diving conditions the tracer pool displayed radically different specific activity curves indicative of the changes in perfusion and metabolic rate associated with a strong dive response. Since the radiotracer curves during exercise and diving differed qualitatively and quantitatively, it is possible that similar studies on freely diving animals can be used to assess the role of the diving response during underwater swimming in nature.

Role of fusiform and anterior temporal cortical areas in facial recognition.

PubMed

Nasr, Shahin; Tootell, Roger B H

2012-11-15

Recent fMRI studies suggest that cortical face processing extends well beyond the fusiform face area (FFA), including unspecified portions of the anterior temporal lobe. However, the exact location of such anterior temporal region(s), and their role during active face recognition, remain unclear. Here we demonstrate that (in addition to FFA) a small bilateral site in the anterior tip of the collateral sulcus ('AT'; the anterior temporal face patch) is selectively activated during recognition of faces but not houses (a non-face object). In contrast to the psychophysical prediction that inverted and contrast reversed faces are processed like other non-face objects, both FFA and AT (but not other visual areas) were also activated during recognition of inverted and contrast reversed faces. However, response accuracy was better correlated to recognition-driven activity in AT, compared to FFA. These data support a segregated, hierarchical model of face recognition processing, extending to the anterior temporal cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

Time course and specificity of lipolysis in Swiss cheese.

PubMed

Dherbécourt, Julien; Bourlieu, Claire; Maillard, Marie-Bernadette; Aubert-Frogerais, Lydie; Richoux, Romain; Thierry, Anne

2010-11-24

Controlling lipolysis in cheese is necessary to ensure the formation of desirable flavor. To get a better understanding of the mechanism of lipolysis in Swiss cheese, cheeses were manufactured with and without (control) the addition of Propionibacterium freudenreichii. Products of lipolysis were quantified throughout ripening. Half of the free fatty acids (FFA) released in milk (3.66 mg/g fat), in particular the short-chain FFA, were lost in the whey during curd drainage, whereas diglycerides and monoglycerides were retained within the curd. P. freudenreichii was responsible for the release of most FFA during ripening (10.84 and 0.39 mg/g fat in propionibacteria-containing and control cheeses, respectively). Indices of lipolysis displayed low specificity. All types of FFA were released, but butyric and palmitic acids more significantly, which could be due to a low sn-1,3 regioselectivity. All glycerides were hydrolyzed in the following order: monoglycerides>diglycerides>triglycerides. The results of this study show the quantitative and qualitative contributions of the different lipolytic agents to Swiss cheese lipolysis.

Response to glucose and lipid infusions in sepsis: a kinetic analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, J.H.; Wolfe, R.R.

The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U-/sup 14/C-glucose and 1,2, /sup 13/C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of themore » control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model.« less

Support vector machine firefly algorithm based optimization of lens system.

PubMed

Shamshirband, Shahaboddin; Petković, Dalibor; Pavlović, Nenad T; Ch, Sudheer; Altameem, Torki A; Gani, Abdullah

2015-01-01

Lens system design is an important factor in image quality. The main aspect of the lens system design methodology is the optimization procedure. Since optimization is a complex, nonlinear task, soft computing optimization algorithms can be used. There are many tools that can be employed to measure optical performance, but the spot diagram is the most useful. The spot diagram gives an indication of the image of a point object. In this paper, the spot size radius is considered an optimization criterion. Intelligent soft computing scheme support vector machines (SVMs) coupled with the firefly algorithm (FFA) are implemented. The performance of the proposed estimators is confirmed with the simulation results. The result of the proposed SVM-FFA model has been compared with support vector regression (SVR), artificial neural networks, and generic programming methods. The results show that the SVM-FFA model performs more accurately than the other methodologies. Therefore, SVM-FFA can be used as an efficient soft computing technique in the optimization of lens system designs.

Role of Fusiform and Anterior Temporal Cortical Areas in Facial Recognition

PubMed Central

Nasr, Shahin; Tootell, Roger BH

2012-01-01

Recent FMRI studies suggest that cortical face processing extends well beyond the fusiform face area (FFA), including unspecified portions of the anterior temporal lobe. However, the exact location of such anterior temporal region(s), and their role during active face recognition, remain unclear. Here we demonstrate that (in addition to FFA) a small bilateral site in the anterior tip of the collateral sulcus (‘AT’; the anterior temporal face patch) is selectively activated during recognition of faces but not houses (a non-face object). In contrast to the psychophysical prediction that inverted and contrast reversed faces are processed like other non-face objects, both FFA and AT (but not other visual areas) were also activated during recognition of inverted and contrast reversed faces. However, response accuracy was better correlated to recognition-driven activity in AT, compared to FFA. These data support a segregated, hierarchical model of face recognition processing, extending to the anterior temporal cortex. PMID:23034518

Changes in oxidation indices and minor components of low free fatty acid and freshly extracted crude palm oils under two different storage conditions.

PubMed

Tan, Choon-Hui; Ariffin, Abdul A; Ghazali, Hasanah M; Tan, Chin-Ping; Kuntom, Ainie; Choo, Adrian Cheng-Yong

2017-06-01

This article reports on the changes of oxidation indices and minor components of low free fatty acid (FFA) and freshly extracted crude palm oils after storage at ambient (28 ± 1 C) and 60 C for 77 days. The changes in peroxide value (PV), FFA, extinction coefficient at 233 and 269 nm ( K 233 and K 269 ), bleachability index (DOBI), carotene and vitamin E contents were monitored. PV, FFA, K 233 and K 269 of both oil samples increased as storage progressed while the values of carotene and vitamin E contents decreased. At the end of storage period at 60 °C, the carotene content of low FFA crude palm oil was 4.24 ppm. The storage conditions used led to the loss of entire vitamin E fractions of both oil samples as well as a reduction in DOBI values except for freshly extracted crude palm oil stored at ambient temperature.

The Modification of Fluorescein Angiography and Its Applications in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

PubMed

Peng, Qing; Chen, Yutong; Hua, Rui

2018-06-07

To establish a novel retinal angiography method, red-free angiography (RFA), to investigate retinal changes in age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Following the venous phase of fundus fluorescein angiography (FFA), the detection mode was switched to red-free reflectance to acquire RFA images using the same parameters. RFA showed subretinal fluid, polyps, and outer retinal tubulation, with a higher definition than the FFA and red-free reflectance results. The absorption coefficients in RFA provided more detailed images for AMD and PCV diagnosis. RFA is therefore a promising approach to supplement FFA. © 2018 S. Karger AG, Basel.

Neovascular glaucoma in a patient with X-linked juvenile retinoschisis.

PubMed

Zuo, Chengguo; Chen, Changzheng; Xing, Yiqiao; Du, Lei

2005-09-01

To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS.

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

PubMed

Reyna, Sara M; Ghosh, Sangeeta; Tantiwong, Puntip; Meka, C S Reddy; Eagan, Phyllis; Jenkinson, Christopher P; Cersosimo, Eugenio; Defronzo, Ralph A; Coletta, Dawn K; Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.

Student Leadership Practices of Georgia FFA Success Conference Participants

ERIC Educational Resources Information Center

Ricketts, John C.; Priest, Kerry; Lastly, Ben

2007-01-01

The purpose of this study was to assess the leadership practices or behaviors of FFA members participating in a leadership development workshop known as the Success Conference in Georgia. Leadership practices were determined using the "Student Leadership Practices Inventory" (LPI) (Kouzes & Posner, 1998). While success conference…

Explaining neural signals in human visual cortex with an associative learning model.

PubMed

Jiang, Jiefeng; Schmajuk, Nestor; Egner, Tobias

2012-08-01

"Predictive coding" models posit a key role for associative learning in visual cognition, viewing perceptual inference as a process of matching (learned) top-down predictions (or expectations) against bottom-up sensory evidence. At the neural level, these models propose that each region along the visual processing hierarchy entails one set of processing units encoding predictions of bottom-up input, and another set computing mismatches (prediction error or surprise) between predictions and evidence. This contrasts with traditional views of visual neurons operating purely as bottom-up feature detectors. In support of the predictive coding hypothesis, a recent human neuroimaging study (Egner, Monti, & Summerfield, 2010) showed that neural population responses to expected and unexpected face and house stimuli in the "fusiform face area" (FFA) could be well-described as a summation of hypothetical face-expectation and -surprise signals, but not by feature detector responses. Here, we used computer simulations to test whether these imaging data could be formally explained within the broader framework of a mathematical neural network model of associative learning (Schmajuk, Gray, & Lam, 1996). Results show that FFA responses could be fit very closely by model variables coding for conditional predictions (and their violations) of stimuli that unconditionally activate the FFA. These data document that neural population signals in the ventral visual stream that deviate from classic feature detection responses can formally be explained by associative prediction and surprise signals.

Age-dependent atypicalities in body- and face-sensitive activation of the EBA and FFA in individuals with ASD.

PubMed

Okamoto, Yuko; Kosaka, Hirotaka; Kitada, Ryo; Seki, Ayumi; Tanabe, Hiroki C; Hayashi, Masamichi J; Kochiyama, Takanori; Saito, Daisuke N; Yanaka, Hisakazu T; Munesue, Toshio; Ishitobi, Makoto; Omori, Masao; Wada, Yuji; Okazawa, Hidehiko; Koeda, Tatsuya; Sadato, Norihiro

2017-06-01

Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene. To examine various aspects, we performed individual region of interest (ROI) analysis, as well as conventional random effect group analysis. At individual ROI analysis, we examined the ratio of participants showing a category-sensitive response, the size of regions, location and activation patterns among the four object categories. Adults with ASD showed no atypicalities in activation of the EBA and FFA, whereas children with ASD showed atypical activation in these regions. Specifically, a smaller percentage of children with ASD showed face-sensitive activation of the FFA than TD children. Moreover, the size of the EBA was smaller in children with ASD than in TD children. Our results revealed atypicalities in both the FFA and EBA in children with ASD but not in adults with ASD. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH.

PubMed

Barbero-Becerra, Varenka J; Giraudi, Pablo J; Chávez-Tapia, Norberto C; Uribe, Misael; Tiribelli, Claudio; Rosso, Natalia

2015-10-01

A complex interplay exists between hepatocytes and hepatic stellate cells (HSC) in hepatic fibrogenesis. The activation of HSCs after liver injury leads to production of extracellular matrix (ECM). Co-culture models could be useful to mimic the liver microenvironment. This study evaluates the effect of free fatty acids (FFA) on HSC cells and the interplay with hepatocytes via both soluble-mediator and cell-cell contact. The human hepatocyte cell line (HuH7) and HSC cells (LX2) were exposed to FFA for 24 h in 3 different experimental set-ups: (A) monoculture of HSC; (B) Transwell® system (effect of soluble mediators); and (C) Simultaneous Co-Culture (SCC) (cell-to-cell connections). Intracellular FFA accumulation was assessed qualitatively (microscopy) and quantitatively (flow cytometry); the activation of HSC (alpha smooth muscle actin, α-SMA) expression of ECM components were quantified by RT-PCR. FFA exposure induces intracellular fat accumulation in all the experimental set-up but the expression of α-SMA was significantly increased only in SCC. On the contrary, the expression of ECM was substantially decreased in the transwell® system. The HSC activation is independent of FFA accumulation but requires cell-to-cell interaction with hepatocyte. On the contrary, the gene regulation of ECM components seems to occur through paracrine mediators. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dissociated neural basis of two behavioral hallmarks of holistic face processing: The whole-part effect and composite-face effect.

PubMed

Li, Jin; Huang, Lijie; Song, Yiying; Liu, Jia

2017-07-28

It has been long proposed that our extraordinary face recognition ability stems from holistic face processing. Two widely-used behavioral hallmarks of holistic face processing are the whole-part effect (WPE) and composite-face effect (CFE). However, it remains unknown whether these two effects reflect similar or different aspects of holistic face processing. Here we investigated this question by examining whether the WPE and CFE involved shared or distinct neural substrates in a large sample of participants (N=200). We found that the WPE and CFE showed hemispheric dissociation in the fusiform face area (FFA), that is, the WPE was correlated with face selectivity in the left FFA, while the CFE was correlated with face selectivity in the right FFA. Further, the correlation between the WPE and face selectivity was largely driven by the FFA response to faces, whereas the association between the CFE and face selectivity resulted from suppressed response to objects in the right FFA. Finally, we also observed dissociated correlation patterns of the WPE and CFE in other face-selective regions and across the whole brain. These results suggest that the WPE and CFE may reflect different aspects of holistic face processing, which shed new light on the behavioral dissociations of these two effects demonstrated in literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles

PubMed Central

Lara, Giovanna Gomes; Andrade, Gracielle Ferreira; da Silva, Wellington Marcos

2018-01-01

Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium–iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones. PMID:29315235

Total Program Efficacy: A Comparison of Traditionally and Alternatively Certified Agriculture Teachers

ERIC Educational Resources Information Center

Duncan, Dennis W.; Ricketts, John C.

2008-01-01

The purpose of this study was to determine agriculture teachers' perceived levels of efficacy as they relate to managing the total program of agricultural education, both for traditionally and alternatively certified teachers. The constructs used in this study were technical content, FFA/leadership development/SAE, teaching and learning, and…

A framework for multivariate data-based at-site flood frequency analysis: Essentiality of the conjugal application of parametric and nonparametric approaches

NASA Astrophysics Data System (ADS)

Vittal, H.; Singh, Jitendra; Kumar, Pankaj; Karmakar, Subhankar

2015-06-01

In watershed management, flood frequency analysis (FFA) is performed to quantify the risk of flooding at different spatial locations and also to provide guidelines for determining the design periods of flood control structures. The traditional FFA was extensively performed by considering univariate scenario for both at-site and regional estimation of return periods. However, due to inherent mutual dependence of the flood variables or characteristics [i.e., peak flow (P), flood volume (V) and flood duration (D), which are random in nature], analysis has been further extended to multivariate scenario, with some restrictive assumptions. To overcome the assumption of same family of marginal density function for all flood variables, the concept of copula has been introduced. Although, the advancement from univariate to multivariate analyses drew formidable attention to the FFA research community, the basic limitation was that the analyses were performed with the implementation of only parametric family of distributions. The aim of the current study is to emphasize the importance of nonparametric approaches in the field of multivariate FFA; however, the nonparametric distribution may not always be a good-fit and capable of replacing well-implemented multivariate parametric and multivariate copula-based applications. Nevertheless, the potential of obtaining best-fit using nonparametric distributions might be improved because such distributions reproduce the sample's characteristics, resulting in more accurate estimations of the multivariate return period. Hence, the current study shows the importance of conjugating multivariate nonparametric approach with multivariate parametric and copula-based approaches, thereby results in a comprehensive framework for complete at-site FFA. Although the proposed framework is designed for at-site FFA, this approach can also be applied to regional FFA because regional estimations ideally include at-site estimations. The framework is based on the following steps: (i) comprehensive trend analysis to assess nonstationarity in the observed data; (ii) selection of the best-fit univariate marginal distribution with a comprehensive set of parametric and nonparametric distributions for the flood variables; (iii) multivariate frequency analyses with parametric, copula-based and nonparametric approaches; and (iv) estimation of joint and various conditional return periods. The proposed framework for frequency analysis is demonstrated using 110 years of observed data from Allegheny River at Salamanca, New York, USA. The results show that for both univariate and multivariate cases, the nonparametric Gaussian kernel provides the best estimate. Further, we perform FFA for twenty major rivers over continental USA, which shows for seven rivers, all the flood variables followed nonparametric Gaussian kernel; whereas for other rivers, parametric distributions provide the best-fit either for one or two flood variables. Thus the summary of results shows that the nonparametric method cannot substitute the parametric and copula-based approaches, but should be considered during any at-site FFA to provide the broadest choices for best estimation of the flood return periods.

Global changes in the proteome of Cupriavidus necator H16 during poly-(3-hydroxybutyrate) synthesis from various biodiesel by-product substrates.

PubMed

Sharma, Parveen K; Fu, Jilagamazhi; Spicer, Victor; Krokhin, Oleg V; Cicek, Nazim; Sparling, Richard; Levin, David B

2016-12-01

Synthesis of poly-[3-hydroxybutyrate] (PHB) by Cupriavidus necator H16 in batch cultures was evaluated using three biodiesel-derived by-products as the sole carbon sources: waste glycerol (REG-80, refined to 80 % purity with negligible free fatty acids); glycerol bottom (REG-GB, with up to 65 % glycerol and 35 % free fatty acids), and free fatty acids (REG-FFA, with up to 75 % FFA and no glycerol). All the three substrates supported growth and PHB production by C. necator, with polymer accumulation ranging from 9 to 84 % cell dry weight (cdw), depending on the carbon source. To help understand these differences, proteomic analysis indicated that although C. necator H16 was able to accumulate PHB during growth on all three biodiesel by-products, no changes in the levels of PHB synthesis enzymes were observed. However, significant changes in the levels of expression were observed for two Phasin proteins involved with PHB accumulation, and for a number of gene products in the fatty acid β-oxidation pathway, the Glyoxylate Shunt, and the hydrogen (H2) synthesis pathways in C. necator cells cultured with different substrates. The glycerol transport protein (GlpF) was induced in REG-GB and REG-80 glycerol cultures only. Cupriavidus necator cells cultured with REG-GB and REG-FFA showed up-regulation of β-oxidation and Glyoxylate Shunt pathways proteins at 24 h pi, but H2 synthesis pathways enzymes were significantly down-regulated, compared with cells cultured with waste glycerol. Our data confirmed earlier observations of constitutive expression of PHB synthesis proteins, but further suggested that C. necator H16 cells growing on biodiesel-derived glycerol were under oxidative stress.

Metabolic fate of glucose and candidate signaling and excess-fuel detoxification pathways in pancreatic β-cells

PubMed Central

Mugabo, Yves; Zhao, Shangang; Lamontagne, Julien; Al-Mass, Anfal; Peyot, Marie-Line; Corkey, Barbara E.; Joly, Erik; Madiraju, S. R. Murthy; Prentki, Marc

2017-01-01

Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mm glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mm glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose-dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS-1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to triglycerides and cholesterol esters. PMID:28280244

26 CFR 1.597-5 - Taxable Transfers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... has a positive balance in a deferred FFA account (see § 1.597-2(c)(4)(v) regarding the optional accelerated recapture of deferred FFA); or (iv) With respect to a Consolidated Subsidiary, while the... Guarantees, yield maintenance payments, cost to carry or cost of funds reimbursement payments, or expense...

26 CFR 1.597-5 - Taxable Transfers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... has a positive balance in a deferred FFA account (see § 1.597-2(c)(4)(v) regarding the optional accelerated recapture of deferred FFA); or (iv) With respect to a Consolidated Subsidiary, while the... Guarantees, yield maintenance payments, cost to carry or cost of funds reimbursement payments, or expense...

26 CFR 1.597-5 - Taxable Transfers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... has a positive balance in a deferred FFA account (see § 1.597-2(c)(4)(v) regarding the optional accelerated recapture of deferred FFA); or (iv) With respect to a Consolidated Subsidiary, while the... Guarantees, yield maintenance payments, cost to carry or cost of funds reimbursement payments, or expense...

26 CFR 1.597-5 - Taxable Transfers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... has a positive balance in a deferred FFA account (see § 1.597-2(c)(4)(v) regarding the optional accelerated recapture of deferred FFA); or (iv) With respect to a Consolidated Subsidiary, while the... Guarantees, yield maintenance payments, cost to carry or cost of funds reimbursement payments, or expense...

Isolation of the molecular species of monogalactosyldiacylglycerols from brown edible seaweed Sargassum horneri and their inhibitory effects on triglyceride accumulation in 3T3-L1 adipocytes.

PubMed

Ma, Ai-Cui; Chen, Zhen; Wang, Tao; Song, Ni; Yan, Qian; Fang, Yu-Chun; Guan, Hua-Shi; Liu, Hong-Bing

2014-11-19

The chemical composition of monogalactosyldiacylglycerols (MGDGs) from brown alga Sargassum horneri and their inhibitory effects on lipid accumulation were investigated in this study. A total of 10 molecular species of MGDGs were identified using nuclear magnetic resonance, alkaline hydrolysis, gas chromatography-flame ionization detector, and high-performance liquid chromatography-tandem mass spectrometry methods. Individual molecular species of MGDGs, including (2S)-1-O-myristoyl-2-O-palmitoleoyl-3-O-β-D-galactopyranosyl-sn-glycerol (1), (2S)-1-O-myristoyl-2-O-linoleyl-3-O-β-D-galactopyranosyl-sn-glycerol (3), (2S)-1-O-palmitoyl-2-O-linolenoyl-3-O-β-D-galactopyranosyl-sn-glycerol (5), (2S)-1-O-myristoyl-2-O-oleyl-3-O-β-D-galactopyranosyl-sn-glycerol (7), (2S)-1-O-palmitoyl-2-O-palmitoleoyl-3-O-β-D-galactopyranosyl-sn-glycerol (8), (2S)-1-O-palmitoyl-2-O-linoleyl-3-O-β-D-galactopyranosyl-sn-glycerol (9), and (2S)-1-O-palmitoyl-2-O-oleyl-3-O-β-D-galactopyranosyl-sn-glycerol (10), were then furnished using semi-preparative high-performance liquid chromatography, and their inhibitory effects on triglyceride (TG) accumulation and free fatty acid (FFA) levels in 3T3-L1 adipocytes were evaluated. Compounds 3 and 9 showed inhibitory effects on TG and FFA accumulation, with TG levels of 1.568 ± 0.2808 and 1.701 ± 0.1460 μmol/L and FFA levels of 0.149 ± 0.0258 and 0.198 ± 0.0229 mequiv/L, respectively, which were more effective than other compounds. The primary structure-activity relationship suggested that linoleyl [18:2(ω-6)] in the sn-2 position played an important role on triglyceride accumulation inhibition.

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated proteinmore » kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty acid. • Honokiol induces the phosphorylation of AMPK and ACC and inhibits SREBP-1c maturation. • LKB1–AMPK signaling pathway mediates anti-lipogenic effect of honokiol in hepatocyte. • Honokiol activates LKB1 and AMPK and inhibits nonalcoholic steatosis in HFD-fed mice.« less

Proceedings of the Annual National Agricultural Education Research Meeting (12th, Atlanta, Georgia, December 6, 1985).

ERIC Educational Resources Information Center

American Vocational Association, Arlington, VA. Agricultural Education Div.

These proceedings include the following papers: "An Assessment of the National FFA Public Service Announcement Program" (Sutphin, Dillon, and Rush); "Educational Objectives and Administrative Criteria for the National FFA Contest Program" (Smith and Kahler); "A National Profile of Agricultural Teacher Educators and State Supervisors of Vocational…

Texas Future Farmers of America Poultry Judging Handbook. Revised.

ERIC Educational Resources Information Center

Bradley, J. W.; And Others

This handbook is designed to help students in Texas prepare for Future Farmers of America (FFA) poultry judgings. The handbook is organized into five major sections that cover the following topics: organization of the Texas FFA poultry judging contest; judging production hens; judging production pullets; grading ready-to-cook broilers, fryers, or…

A Comparative Analysis of College Readiness Assessment Results of Illinois High School Agriculture Students

ERIC Educational Resources Information Center

Mouser, David M.; Sheng, Zhaohui; Thoron, Andrew C.; Baker, Andy; Bacon, Kevin J.

2017-01-01

Agricultural education is defined by a best practice three-component model of instruction that includes a classroom experience, leadership development and FFA involvement, and an experience-based activity through a Supervised Agricultural Experience program (SAE). Based on program of activities award criteria, each year state FFA associations…

Youth Leadership Development through School-Based Civic Engagement Activities: A Case Study

ERIC Educational Resources Information Center

Horstmeier, Robin Peiter; Ricketts, Kristina G.

2009-01-01

Leadership development through a civic engagement activity in a local FFA chapter is explored. Through a case study design, researchers illuminate a project that encouraged youth leadership development through the creation and execution of a civic engagement project in their own local community. Holistically, FFA members viewed the project as a…

Chapter Innovators Guide, 2000: Models of Innovation Award Winners.

ERIC Educational Resources Information Center

National FFA Organization, Indianapolis, IN.

This guide presents the Future Farmers of America (FFA) 2000 Model of Innovation award winners' projects. Chapters demonstrated abilities to identify goals and objectives, create a workable plan of action, attain and evaluate results, and identify items learned and ways to improve. Chapter 1 discusses the FFA National Chapter Award program that…

26 CFR 1.597-2 - Taxation of Federal financial assistance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this section. (4) Deferred FFA—(i) Maintenance of account. An Institution must establish a deferred FFA... currently under certain circumstances and provides rules for the deferred inclusion in income of amounts in... not currently included in income under paragraph (c)(2) or (c)(3) of this section to its deferred FFA...

26 CFR 1.597-2 - Taxation of Federal financial assistance.

Code of Federal Regulations, 2012 CFR

2012-04-01

... this section. (4) Deferred FFA—(i) Maintenance of account. An Institution must establish a deferred FFA... currently under certain circumstances and provides rules for the deferred inclusion in income of amounts in... not currently included in income under paragraph (c)(2) or (c)(3) of this section to its deferred FFA...

26 CFR 1.597-2 - Taxation of Federal financial assistance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this section. (4) Deferred FFA—(i) Maintenance of account. An Institution must establish a deferred FFA... currently under certain circumstances and provides rules for the deferred inclusion in income of amounts in... not currently included in income under paragraph (c)(2) or (c)(3) of this section to its deferred FFA...

Leadership Curriculum and Materials Used by High School Agricultural Science Teachers: A National Study of the Pre-"LifeKnowledge" Days

ERIC Educational Resources Information Center

Morgan, A. Christian; Fuhrman, Nicholas E.; King, Diana L.; Flanders, Frank B.; Rudd, Rick D.

2013-01-01

Agricultural science programs have provided many opportunities for leadership education through classroom, supervised agricultural experience (SAE), and FFA Organization activities. Past studies have focused on leadership developed through activities such as career development events (CDE), SAE activities, FFA Organization conventions, and other…

Distinct representations of configural and part information across multiple face-selective regions of the human brain

PubMed Central

Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

2015-01-01

Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

One-step production of biodiesel from rice bran oil catalyzed by chlorosulfonic acid modified zirconia via simultaneous esterification and transesterification.

PubMed

Zhang, Yue; Wong, Wing-Tak; Yung, Ka-Fu

2013-11-01

Due to the high content (25-50%) of free fatty acid (FFA), crude rice bran oil usually requires a two steps conversion or one step conversion with very harsh condition for simultaneous esterification and transesterification. In this study, chlorosulfonic acid modified zirconia (HClSO3-ZrO2) with strong acidity and durability is prepared and it shows excellent catalytic activity toward simultaneous esterification and transesterification. Under a relative low reaction temperature of 120 °C, HClSO3-ZrO2 catalyzes a complete conversion of simulated crude rice bran oil (refined oil with 40 wt% FFA) into biodiesel and the conversion yield keep at above 92% for at least three cycles. Further investigation on the tolerance towards FFA and water reveals that it maintains high activity even with the presence of 40 wt% FFA and 3 wt% water. It shows that HClSO3-ZrO2 is a robust and durable catalyst which shows high potential to be commercial catalyst for biodiesel production from low grade feedstock. Copyright © 2013 Elsevier Ltd. All rights reserved.

River flow simulation using a multilayer perceptron-firefly algorithm model

NASA Astrophysics Data System (ADS)

Darbandi, Sabereh; Pourhosseini, Fatemeh Akhoni

2018-06-01

River flow estimation using records of past time series is importance in water resources engineering and management and is required in hydrologic studies. In the past two decades, the approaches based on the artificial neural networks (ANN) were developed. River flow modeling is a non-linear process and highly affected by the inputs to the modeling. In this study, the best input combination of the models was identified using the Gamma test then MLP-ANN and hybrid multilayer perceptron (MLP-FFA) is used to forecast monthly river flow for a set of time intervals using observed data. The measurements from three gauge at Ajichay watershed, East Azerbaijani, were used to train and test the models approach for the period from January 2004 to July 2016. Calibration and validation were performed within the same period for MLP-ANN and MLP-FFA models after the preparation of the required data. Statistics, the root mean square error and determination coefficient, are used to verify outputs from MLP-ANN to MLP-FFA models. The results show that MLP-FFA model is satisfactory for monthly river flow simulation in study area.

Effective connectivity of facial expression network by using Granger causality analysis

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Xiaoting

2013-10-01

Functional magnetic resonance imaging (fMRI) is an advanced non-invasive data acquisition technique to investigate the neural activity in human brain. In addition to localize the functional brain regions that is activated by specific cognitive task, fMRI can also be utilized to measure the task-related functional interactions among the active regions of interest (ROI) in the brain. Among the variety of analysis tools proposed for modeling the connectivity of brain regions, Granger causality analysis (GCA) measure the directions of information interactions by looking for the lagged effect among the brain regions. In this study, we use fMRI and Granger Causality analysis to investigate the effective connectivity of brain network induced by viewing several kinds of expressional faces. We focus on four kinds of facial expression stimuli: fearful, angry, happy and neutral faces. Five face selective regions of interest are localized and the effective connectivity within these regions is measured for the expressional faces. Our result based on 8 subjects showed that there is significant effective connectivity from STS to amygdala, from amygdala to OFA, aFFA and pFFA, from STS to aFFA and from pFFA to aFFA. This result suggested that there is an information flow from the STS to the amygdala when perusing expressional faces. This emotional expressional information flow that is conveyed by STS and amygdala, flow back to the face selective regions in occipital-temporal lobes, which constructed a emotional face processing network.

Morphological and topographical appearance of microaneurysms on optical coherence tomography angiography.

PubMed

Schreur, Vivian; Domanian, Artin; Liefers, Bart; Venhuizen, Freerk G; Klevering, B Jeroen; Hoyng, Carel B; de Jong, Eiko K; Theelen, Thomas

2018-06-20

To investigate retinal microaneurysms in patients with diabetic macular oedema (DME) by optical coherence tomography angiography (OCTA) according to their location and morphology in relationship to their clinical properties, leakage on fundus fluorescein angiography (FFA) and retinal thickening on structural OCT. OCTA and FFA images of 31 eyes of 24 subjects were graded for the presence of microaneurysms. The topographical and morphological appearance of microaneurysms on OCTA was evaluated and classified. For each microaneurysm, the presence of focal leakage on FFA and associated retinal thickening on OCT was determined. Of all microaneurysms flagged on FFA, 295 out of 513 (58%) were also visible on OCTA. Microaneurysms with focal leakage and located in a thickened retinal area were more likely to be detected on OCTA than not leaking microaneurysms in non-thickened retinal areas (p=0.001). Most microaneurysms on OCTA were seen in the intermediate (23%) and deep capillary plexus (22%). Of all microaneurysms visualised on OCTA, saccular microaneurysms were detected most often (31%), as opposed to pedunculated microaneurysms (9%). Irregular, fusiform and mixed fusiform/saccular-shaped microaneurysms had the highest likeliness to leak and to be located in thickened retinal areas (p<0.001, p<0.001 and p=0.001). Retinal microaneurysms in DME could be classified topographically and morphologically by OCTA. OCTA detected less microaneurysms than FFA, and this appeared to be dependent on leakage activity and retinal thickening. Morphological appearance of microaneurysms (irregular, fusiform and mixed saccular/fusiform) was associated with increased leakage activity and retinal thickening.

Liver free fatty acid (FFA) accumulation as an indicator of ischemic injury during cold preservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemoto, E.M.; Kang, Y.; DeWolf, A.M.

1987-05-01

Reliable assessment of hepatic viability prior to harvest and transplant could improve graft success and aid in evaluating the efficacy of liver preservation techniques. Hepatic tissue metabolites, protein (Pr) synthesis, and ATP have been studied, but none reliably correlate with hepatic viability. Therefore, they studied changes in liver FFA relative to changes in ATP and Pr synthesis during cold ischemic preservation. Rats mechanically ventilated on 0.5% isoflurane/70% N/sub 2/O/30% O/sub 2/ were heparinized and their livers perfused with air-equilibrated Euro-Collins solution (ECS) at 0-4/sup 0/C and kept on ice. A piece of the liver was removed after 0, 2, 6,more » 8, 12, 24, 36 and 48 h of preservation for ATP and FFA analysis. A portion of the liver was sliced (250 ..mu..m thick) and incubated in vitro for /sup 14/C-lysine incorporation in albumin. ATP, FFA and Pr synthesis were unchanged in the first 8 h, but markedly decreased between 8 and 12 h with little change thereafter. In contrast, between 8 and 48 h, arachidonic and stearic acids increased by 5 and 2-fold, respectively. Changes in ATP and Pr synthesis correlate with the empirically derived clinical maximum of 8 to 12 h preservation. FFA accumulation appears to reflect hepatic ischemic injury and may be a means of evaluating the quality of a donor liver.« less

Reducing uncertainty with flood frequency analysis: The contribution of paleoflood and historical flood information

NASA Astrophysics Data System (ADS)

Lam, Daryl; Thompson, Chris; Croke, Jacky; Sharma, Ashneel; Macklin, Mark

2017-03-01

Using a combination of stream gauge, historical, and paleoflood records to extend extreme flood records has proven to be useful in improving flood frequency analysis (FFA). The approach has typically been applied in localities with long historical records and/or suitable river settings for paleoflood reconstruction from slack-water deposits (SWDs). However, many regions around the world have neither extensive historical information nor bedrock gorges suitable for SWDs preservation and paleoflood reconstruction. This study from subtropical Australia demonstrates that confined, semialluvial channels such as macrochannels provide relatively stable boundaries over the 1000-2000 year time period and the preserved SWDs enabled paleoflood reconstruction and their incorporation into FFA. FFA for three sites in subtropical Australia with the integration of historical and paleoflood data using Bayesian Inference methods showed a significant reduction in uncertainty associated with the estimated discharge of a flood quantile. Uncertainty associated with estimated discharge for the 1% Annual Exceedance Probability (AEP) flood is reduced by more than 50%. In addition, sensitivity analysis of possible within-channel boundary changes shows that FFA is not significantly affected by any associated changes in channel capacity. Therefore, a greater range of channel types may be used for reliable paleoflood reconstruction by evaluating the stability of inset alluvial units, thereby increasing the quantity of temporal data available for FFA. The reduction in uncertainty, particularly in the prediction of the ≤1% AEP design flood, will improve flood risk planning and management in regions with limited temporal flood data.

Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R.

PubMed

Sundqvist, Martina; Christenson, Karin; Holdfeldt, André; Gabl, Michael; Mårtensson, Jonas; Björkman, Lena; Dieckmann, Regis; Dahlgren, Claes; Forsman, Huamei

2018-05-01

GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo. In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances

PubMed Central

Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

2013-01-01

The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p < 0.05. The following results were obtained from this study; 1. In the change of fatigue substances : Serotonin in the EXP tended to decreased at the 10 min before exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in the CON was significantly greater than the EXP at the10 min before exercise and recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30 min into exercise, and post exercise, but significantly decreased at the recovery 30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the 10 min before exercise, 30 min into exercise, and post exercise (p < 0.05). Lactate in the EXP was significantly increased at the 30 min into exercise and significantly decreased at the post exercise and recovery 30 min. Lactate in the CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In the change of muscle damage substances : CK in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. CK in the CON was greater than the EXP. LDH in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. LDH in the CON was higher than the EXP. 3. In the change of energy metabolism substances :Glucose in the EXP tended to decrease at the 10 min before exercise, 30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both EXP and CON was increased at the post exercise and recovery 30 min. % increase for FFA in the EXP was greater than the CON at the post exercise and recovery 30 min. 4. The relationship of the fatigue substances, muscle damage substances and energy metabolism substances after endurance exercise indicated strongly a positive relationship between LDH and ammonia and a negative relationship between LDH and FFA in the EXP. Also, there were a strong negative relationship between glucose and FFA and a positive relationship between glucose and serotonin in the EXP. There was a strong positive relationship between CK and LDH and a strong negative relationship between FFA and glucose in the CON. These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise. PMID:25566428

Effect of BCAA intake during endurance exercises on fatigue substances, muscle damage substances, and energy metabolism substances.

PubMed

Kim, Dong-Hee; Kim, Seok-Hwan; Jeong, Woo-Seok; Lee, Ha-Yan

2013-12-01

The increase rate of utilization of branched-chain amino acids (BCAA) by muscle is reduced to its plasma concentration during prolonged exercise leading to glycogen. BCAA supplementation would reduce the serum activities of intramuscular enzymes associated with muscle damage. To examine the effects of BCAA administration on fatigue substances (serotonin, ammonia and lactate), muscle damage substances (CK and LDH) and energy metabolism substances (FFA and glucose) after endurance exercise. Subjects (n = 26, college-aged males) were randomly divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group. Subjects both EXP and CON performed a bout of cycle training (70% VO2max intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg·w) prior to the bout of cycle exercise. Fatigue substances, muscle damage substances and energy metabolism substances were measured before ingesting BCAAs and placebos, 10 min before exercise, 30 min into exercise, immediately after exercise, and 30 min after exercise. Data were analyzed by two-way repeated measure ANCOVA, correlation and statistical significance was set at p < 0.05. The following results were obtained from this study; 1. In the change of fatigue substances : Serotonin in the EXP tended to decreased at the 10 min before exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in the CON was significantly greater than the EXP at the10 min before exercise and recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30 min into exercise, and post exercise, but significantly decreased at the recovery 30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the 10 min before exercise, 30 min into exercise, and post exercise (p < 0.05). Lactate in the EXP was significantly increased at the 30 min into exercise and significantly decreased at the post exercise and recovery 30 min. Lactate in the CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In the change of muscle damage substances : CK in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. CK in the CON was greater than the EXP. LDH in the EXP was decreased at the 10 min before exercise and increased at the 30 min into exercise and then decreased at the post exercise and recovery 30 min. LDH in the CON was higher than the EXP. 3. In the change of energy metabolism substances :Glucose in the EXP tended to decrease at the 10 min before exercise, 30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both EXP and CON was increased at the post exercise and recovery 30 min. % increase for FFA in the EXP was greater than the CON at the post exercise and recovery 30 min. 4. The relationship of the fatigue substances, muscle damage substances and energy metabolism substances after endurance exercise indicated strongly a positive relationship between LDH and ammonia and a negative relationship between LDH and FFA in the EXP. Also, there were a strong negative relationship between glucose and FFA and a positive relationship between glucose and serotonin in the EXP. There was a strong positive relationship between CK and LDH and a strong negative relationship between FFA and glucose in the CON. These results indicate that supplementary BCAA decreased serum concentrations of the intramuscular enzymes as CK and LDH following exhaustive exercise. This observation suggests that BCAA supplementation may reduce the muscle damage associated with endurance exercise.

Career Development Event Preparation and Experiential Learning Strategies Employed by Pennsylvania Secondary Agricultural Education Teachers

ERIC Educational Resources Information Center

Ewing, John C.; Clark, Robert W.; Threeton, Mark D.

2014-01-01

Career development events are an important facet of the National FFA organization as well as the teaching and learning segment of the national research agenda for Career and Technical Education (Lambeth, Elliot & Joerger, 2008). Students are often prepared to compete in these events by their FFA advisor. Career development events provide…

Perceived Leadership Life Skills Developed through Participation at the Arkansas FFA Leadership Conference: A Program Evaluation

ERIC Educational Resources Information Center

Ahrens, Chelsey Ann; Cox, Casandra Kay; Burris, Scott; Dykes, Mollie

2015-01-01

Youth leadership life skills are the "development of life skills necessary to perform leadership functions in real life" (Miller, 1976, p.2). A model developed by Kapostasy indicates life skills should be taught through FFA [formerly Future Farmers of America] (Staller, 2001). Thus, it is important to evaluate youth leadership life…

Chapter Innovators Guide, 2001: Models of Innovation Award Winners.

ERIC Educational Resources Information Center

National FFA Organization, Indianapolis, IN.

This document presents the activities that received Future Farmers of America's (FFA's) Model of Innovation awards in 2001. The booklet begins with an overview of the FFA National Chapter Award program and a list of the 2001 Models of Innovation Winners. The next three sections profile award-winning activities in the following areas of the three…

Fundraising: Does It Have To Be Painful?

ERIC Educational Resources Information Center

Rush, Michael G.

Some guidelines can make fundraising by Future Farmers of America (FFA) chapters easier and more productive. The first question to be asked is what the FFA chapter wants to accomplish and how much it will cost. Once the goal is set, an appropriate project can be adopted. Criteria for selecting projects include the following: (1) Does the project…

Shuttle program. STS-7 feasibility assessment: IUS/TDRS-A

NASA Technical Reports Server (NTRS)

1979-01-01

This Space Transportation System 7 (STS-7) Flight Feasibility Assessment (FFA) provides a base from which the various design, operation, and integration elements associated with Tracking and Data Relay Satellite-A can perform mission planning and analysis. The STS-7 FFA identifies conflicts, issues, and concerns associated with the integrated flight design requirements and constraints.

A contrarian view of the five-factor approach to personality description.

PubMed

Block, J

1995-03-01

The 5-factor approach (FFA) to personality description has been represented as a comprehensive and compelling rubric for assessment. In this article, various misgivings about the FFA are delineated. The algorithmic method of factor analysis may not provide dimensions that are incisive. The "discovery" of the five factors may be influenced by unrecognized constraints on the variable sets analyzed. Lexical analyses are based on questionable conceptual and methodological assumptions, and have achieved uncertain results. The questionnaire version of the FFA has not demonstrated the special merits and sufficiencies of the five factors settled upon. Serious uncertainties have arisen in regard to the claimed 5-factor structure and the substantive meanings of the factors. Some implications of these problems are drawn.

Dissecting contributions of prefrontal cortex and fusiform face area to face working memory.

PubMed

Druzgal, T Jason; D'Esposito, Mark

2003-08-15

Interactions between prefrontal cortex (PFC) and stimulus-specific visual cortical association areas are hypothesized to mediate visual working memory in behaving monkeys. To clarify the roles for homologous regions in humans, event-related fMRI was used to assess neural activity in PFC and fusiform face area (FFA) of subjects performing a delay-recognition task for faces. In both PFC and FFA, activity increased parametrically with memory load during encoding and maintenance of face stimuli, despite quantitative differences in the magnitude of activation. Moreover, timing differences in PFC and FFA activation during memory encoding and retrieval implied a context dependence in the flow of neural information. These results support existing neurophysiological models of visual working memory developed in the nonhuman primate.

Impaired glucose tolerance in patients with amyotrophic lateral sclerosis.

PubMed

Pradat, Pierre-Francois; Bruneteau, Gaelle; Gordon, Paul H; Dupuis, Luc; Bonnefont-Rousselot, Dominique; Simon, Dominique; Salachas, Francois; Corcia, Philippe; Frochot, Vincent; Lacorte, Jean-Marc; Jardel, Claude; Coussieu, Christiane; Le Forestier, Nadine; Lacomblez, Lucette; Loeffler, Jean-Philippe; Meininger, Vincent

2010-01-01

Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

Glycidyl esters in refined palm (Elaeis guineensis) oil and related fractions. Part II: practical recommendations for effective mitigation.

PubMed

Craft, Brian D; Nagy, Kornél; Seefelder, Walburga; Dubois, Mathieu; Destaillats, Frédéric

2012-05-01

In a previous work, it was shown that at high temperatures (up to 280°C) glycidyl esters (GE) are formed from diacylglycerols (DAG) via elimination of free fatty acid (FFA). In the present study, the impact of DAG content and temperature on the formation of GE using a model vacuum system mimicking industrial edible oil deodorization is investigated. These deodorization experiments confirmed that the formation of GE from DAG is extensive at temperatures above 230-240°C, and therefore, this value should be considered as an upper limit for refining operations. Furthermore, experimental data suggest that the formation of GE accelerates in particular when the DAG levels in refined oils exceed 3-4% of total lipids. Analysis of the lipid composition of crude palm oil (CPO) samples allowed the estimation that this critical DAG content corresponds to about 1.9-2.5% of FFA, which is the conventional quality marker of CPO. Moreover, high levels (>100ppm) of GE were also found in palm fatty acid distillate samples, which may indicate that the level of GE in fully refined palm oils also depends on the elimination rate of GE into the fatty acid distillate. Copyright © 2011 Elsevier Ltd. All rights reserved.

Seeing Jesus in toast: Neural and behavioral correlates of face pareidolia

PubMed Central

Liu, Jiangang; Li, Jun; Feng, Lu; Li, Ling; Tian, Jie; Lee, Kang

2014-01-01

Face pareidolia is the illusory perception of non-existent faces. The present study, for the first time, contrasted behavioral and neural responses of face pareidolia with those of letter pareidolia to explore face-specific behavioral and neural responses during illusory face processing. Participants were shown pure-noise images but were led to believe that 50% of them contained either faces or letters; they reported seeing faces or letters illusorily 34% and 38% of the time, respectively. The right fusiform face area (rFFA) showed a specific response when participants “saw” faces as opposed to letters in the pure-noise images. Behavioral responses during face pareidolia produced a classification image that resembled a face, whereas those during letter pareidolia produced a classification image that was letter-like. Further, the extent to which such behavioral classification images resembled faces was directly related to the level of face-specific activations in the right FFA. This finding suggests that the right FFA plays a specific role not only in processing of real faces but also in illusory face perception, perhaps serving to facilitate the interaction between bottom-up information from the primary visual cortex and top-down signals from the prefrontal cortex (PFC). Whole brain analyses revealed a network specialized in face pareidolia, including both the frontal and occipito-temporal regions. Our findings suggest that human face processing has a strong top-down component whereby sensory input with even the slightest suggestion of a face can result in the interpretation of a face. PMID:24583223

Association of postalimentary lipemia with atherosclerotic manifestations.

PubMed

Tentor, J; Nakamura, R T; Gidlund, M; Barros-Mazon, S; Harada, L M; Zago, V S; Oba, J F; Faria, E C de

2012-11-01

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Multivariate pattern dependence

PubMed Central

Saxe, Rebecca

2017-01-01

When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD): a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each brain region as trajectories in region-specific multidimensional spaces, and models the multivariate relationship between these trajectories. We applied MVPD to the posterior superior temporal sulcus (pSTS) and to the fusiform face area (FFA), using a searchlight approach to reveal interactions between these seed regions and the rest of the brain. Across two different experiments, MVPD identified significant statistical dependence not detected by standard functional connectivity. Additionally, MVPD outperformed univariate connectivity in its ability to explain independent variance in the responses of individual voxels. In the end, MVPD uncovered different connectivity profiles associated with different representational subspaces of FFA: the first principal component of FFA shows differential connectivity with occipital and parietal regions implicated in the processing of low-level properties of faces, while the second and third components show differential connectivity with anterior temporal regions implicated in the processing of invariant representations of face identity. PMID:29155809

Effects of plasma adrenaline on hormone-sensitive lipase at rest and during moderate exercise in human skeletal muscle

PubMed Central

Watt, Matthew J; Stellingwerff, Trent; Heigenhauser, George J F; Spriet, Lawrence L

2003-01-01

We investigated the effect of increased plasma adrenaline on hormone-sensitive lipase (HSL) activity and extracellular regulated kinase (ERK) 1/2 phosphorylation during exercise. Seven untrained men rested for 20 min and exercised for 10 min at 60 % peak pulmonary oxygen uptake on three occasions: with adrenaline infusion throughout rest and exercise (ADR), with no adrenaline infusion (CON) and with adrenaline infusion commencing after 3 min of exercise (EX+ADR). Muscle samples were obtained at rest before (Pre, −20 min) and after (0 min) infusion, and at 3 and 10 min of cycling. Exogenous adrenaline infusion increased (P < 0.05) plasma adrenaline at rest during ADR, which resulted in greater HSL activity (Pre, 2.14 ± 0.10 mmol min−1 (kg dry matter (dm))−1; 0 min, 2.74 ± 0.20 mmol min−1 (kg dm)−1). Subsequent exercise had no effect on HSL activity. During exercise in CON, HSL activity was increased (P < 0.05) above rest at 3 min but was not increased further by 10 min. The infusion of exogenous adrenaline at 3 min of exercise in EX+ADR resulted in a marked elevation in plasma adrenaline levels (3 min, 0.57 ± 0.12 nM; 10 min, 10.08 ± 0.84 nM) and increased HSL activity by 25 %. HSL activity at 10 min was greater (P < 0.05) in EX+ADR compared with CON. There were no changes between trials in the plasma concentrations of insulin and free fatty acids (FFA) and the muscle contents of free AMP, all putative regulators of HSL activity. ERK1/2 phosphorylation increased at 3 min in CON and EX+ADR. Because HSL activity did not increase during exercise when adrenaline was infused prior to exercise (ADR) and because HSL activity increased when adrenaline was infused during exercise (EX+ADR), we conclude that (1) high adrenaline levels can stimulate HSL activity regardless of the metabolic milieu and (2) large increases in adrenaline during exercise, independent of changes in other putative regulators, are able to further stimulate the contraction-induced increase in HSL activity. The results also demonstrate that increased ERK 1/2 phosphorylation coincides with elevated HSL activity, indicating that ERK 1/2 may mediate the contraction-induced increase in HSL activity early in exercise. PMID:12730334

Regulatory mechanism of mineral-balanced deep sea water on hypocholesterolemic effects in HepG2 hepatic cells.

PubMed

Lee, Kyu-Shik; Kwon, Yun-Suk; Kim, Soyoung; Moon, Deok-Soo; Kim, Hyeon Ju; Nam, Kyung-Soo

2017-02-01

Several previous studies have shown the benefits of deep sea water (DSW) in lipid metabolism. However, the effects of DSW on cellular cholesterol accumulation and synthesis induced by high glucose or free fatty acid plus high glucose [4.5g/L] (FFA/glucose) have not been fully elucidated to date. Herein, we showed the effects of mineral-balanced DSW [magnesium (Mg):calcium (Ca)=3:1] (MB-DSW) on cholesterol metabolism induced by high glucose or FFA/glucose in HepG2 hepatic cells. Moreover, the effects of high ratio Mg DSW [Mg:Ca=40:1] (Mg40) were also investigated. MB-DSW and Mg40 prevented the increase of cellular total cholesterol content in high glucose- or FFA/glucose-treated HepG2 hepatic cells. Furthermore, the inhibition by MB-DSW was closely related to the down-regulation of 3-hydroxy-3-methylglutatryl-CoA reductase (HMGCR) expression and an increase in the AMP-activated protein kinase (AMPK) phosphorylation, leading to decreased cholesterol synthesis in both high glucose- and FFA/glucose-treated conditions. However, this effect was not seen in case of Mg40. In addition, both MB-DSW and Mg40 induced the low-density lipoprotein receptor (LDLR) and diminished the proprotein convertase subtilisin/kexin type 9 (PCSK9) transcriptions in high glucose-treated HepG2 hepatic cells. This result demonstrates that the hypocholesterolemic effects of MB-DSW and Mg40 are mediated with LDL-c clearance through increases of LDLR and its transcription factors, such as peroxisome proliferator-activated receptor-α (PPAR-α), sterol regulatory element-binding protein (SREBP)-1a, and SREBP-2, mRNA synthesis and suppression of PCSK9 transcription. Moreover, apolipoprotein (Apo) A1 transcription was enhanced by MB-DSW and Mg40 without decreasing the expression of Apo B in high glucose-treated HepG2 hepatic cells. However, ApoA1 protein expression was not changed. Taken together, the present investigation suggests that DSW may prevent the high glucose- or FFA/glucose-induced increase of cellular cholesterol levels by inducing LDLR and ApoA1 transcriptions and inhibiting PCSK9 mRNA expression in HepG2 hepatic cells. Additionally, the ratio of Mg in DSW is an important factor that determines whether HMGCR expression and/or AMPK phosphorylation participate in the hypocholesterolemic effects of DSW. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Decreased serum protein binding of diazepam and its major metabolite in the neonate during the first postnatal week relate to increased free fatty acid levels.

PubMed Central

Nau, H; Luck, W; Kuhnz, W

1984-01-01

The protein binding of diazepam (D) and its major active metabolite N-desmethyl diazepam (DD) was investigated in vitro in the serum of 14 mothers at birth, 21 foetuses at birth, in 100 neonates between 1 and 11 days of age and in 16 control subjects. The free (unbound) fractions of D and DD in the foetus were similar to those in the controls, but lower than those in the mothers. During the first day of life the free fractions of D and DD doubled in the neonates and subsequently declined slowly to reach near control levels at 1 week of age. The sharp increase and slow decrease of the free fractions of D and DD during the first postnatal week was closely paralleled by sharply increasing and decreasing free fatty acid (FFA) concentrations. Bilirubin and albumin levels were of lower importance in regard to the protein binding of D and DD. These results indicate that the greatly increased FFA levels shortly after birth result in increased free fractions of D and DD. Because of the known immaturity of the neonatal hepatic elimination capacity, these elevated free fractions may result in elevated free concentrations of the two compounds, which may help to explain the adverse effects observed clinically in some D-exposed neonates. PMID:6419763

Effects of dietary supplementation with L-carnitine and fat on blood acid-base responses to handling in slaughter weight pigs.

PubMed

Bertol, T M; Ellis, M; Hamilton, D N; Johnson, E W; Ritter, M J

2005-01-01

Blood acid-base responses to handling were evaluated in slaughter weight pigs fed diets supplemented with l-carnitine and fat. The study was carried out as a randomized block design with a 2 x 2 factorial arrangement of treatments: 1) dietary L-carnitine supplementation (0 vs. 150 ppm, as-fed basis); and 2) dietary fat supplementation (0 vs. 5%, as-fed basis). Sixty pigs (91.1 +/- 5.14 kg BW) were housed in mixed-gender groups of five and had ad libitum access to test diets (0.68% true ileal digestible lysine, 3,340 kcal of ME/kg, as-fed basis) for 3 wk. At the end of the feeding period (110.3 +/- 7.52 kg BW), pigs were subjected to a standard handling procedure, which consisted of moving individual animals through a facility (12.2 m long x 0.91 m wide) for eight laps (up and down the facility), using electric prods (two times per lap). There was no interaction between dietary L-carnitine and fat supplementation for any measurement. Pigs fed 150 ppm of supplemental L-carnitine had lower baseline blood glucose (P < 0.05) and higher baseline blood lactate (P < 0.05) concentrations than the nonsupplemented pigs. After handling, pigs fed L-carnitine-supplemented diets had a higher (P < 0.05) blood pH and showed a smaller (P < 0.05) decrease in blood pH and base excess than those fed the nonsupplemental diets. Baseline plasma FFA concentrations were higher (P < 0.01) in pigs fed the 5% fat diet. After the handling procedure, blood glucose, lactate, and plasma FFA were higher (P < 0.05) in pigs fed the 5 vs. 0% fat diets, but blood pH, bicarbonate, and base excess were not affected by dietary fat. The handling procedure decreased (P < 0.01) blood pH, bicarbonate, base excess, and total carbon dioxide and increased (P < 0.01) blood lactate, partial pressure of oxygen, and glucose, and also increased (P < 0.01) rectal temperature. Free fatty acid concentrations were increased by handling in pigs fed both 0 and 5% fat and 150 ppm L-carnitine. In conclusion, dietary L-carnitine supplementation at the level and for the feeding period evaluated in the current study had a relatively small but positive effect on decreasing blood pH changes in finishing pigs submitted to handling stress; however, dietary fat supplementation had little effect on blood acid-base balance.

Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity

PubMed Central

Arulmozhi, Vadivel; Krishnaveni, Mani; Karthishwaran, Kandhan; Dhamodharan, Ganesan; Mirunalini, Sankaran

2010-01-01

The possible protective effect of Solanum nigrum fruit extract (SNFEt) was investigated for its antioxidant and antihyperlipidemic activity against ethanol-induced toxicity in rats. The experimental animals were intoxicated with 20% ethanol (7.9 g/kg/day) for 30 days via gastric intubation. SNFEt was administered at the dose of 250 mg/kg body weight along with the daily dose of ethanol for 30 days. From the result it was observed that ethanol-induced rats showed a significant elevation in the levels of Thiobarbituric acid reactive substances (TBARS), which lowered the antioxidant defense systems, such as, reduced glutathione (GSH) and vitamins C and E, when compared to the controls. In the lipid profiles, the levels of total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL), free fatty acids (FFA), and phospholipids were significantly elevated in the ethanol-induced group, whereas, the high density lipoproteins (HDL) were found to be reduced in the plasma, and the phospholipid levels were significantly decreased in the tissues. Supplementation of SNFEt improved the antioxidant status by decreasing the levels of TBARS and altering the lipid profiles to near normal. These activities were also compared to the standard drug silymarin (25 mg/kg body weight). Thus the findings of the present study indicated a significant antioxidant and antihyperlipidemic activity of Solanum nigrum fruits, which offered protection against ethanol-induced toxicity. PMID:20548935

A microfluidic device for the automated derivatization of free fatty acids to fatty acid methyl esters.

PubMed

Duong, Cindy T; Roper, Michael G

2012-02-21

Free fatty acid (FFA) compositions are examined in feedstock for biodiesel production, as source-specific markers in soil, and because of their role in cellular signaling. However, sample preparation of FFAs for gas chromatography-mass spectrometry (GC-MS) analysis can be time and labor intensive. Therefore, to increase sample preparation throughput, a glass microfluidic device was developed to automate derivatization of FFAs to fatty acid methyl esters (FAMEs). FFAs were delivered to one input of the device and methanolic-HCl was delivered to a second input. FAME products were produced as the reagents traversed a 29 μL reaction channel held at 55 °C. A Design of Experiment protocol was used to determine the combination of derivatization time (T(der)) and ratio of methanolic-HCl:FFA (R(der)) that maximized the derivatization efficiencies of tridecanoic acid and stearic acid to their methyl ester forms. The combination of T(der) = 0.8 min and R(der) = 4.9 that produced optimal derivatization conditions for both FFAs within a 5 min total sample preparation time was determined. This combination of T(der) and R(der) was used to derivatize 12 FFAs with a range of derivatization efficiencies from 18% to 93% with efficiencies of 61% for tridecanoic acid and 84% for stearic acid. As compared to a conventional macroscale derivatization of FFA to FAME, the microfluidic device decreased the volume of methanolic-HCl and FFA by 20- and 1300-fold, respectively. The developed microfluidic device can be used for automated preparation of FAMEs to analyze the FFA compositions of volume-limited samples.

Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.

PubMed Central

Zhou, Y P; Grill, V E

1994-01-01

We tested effects of long-term exposure of pancreatic islets to free fatty acids (FFA) in vitro on B cell function. Islets isolated from male Sprague-Dawley rats were exposed to palmitate (0.125 or 0.25 mM), oleate (0.125 mM), or octanoate (2.0 mM) during culture. Insulin responses were subsequently tested in the absence of FFA. After a 48-h exposure to FFA, insulin secretion during basal glucose (3.3 mM) was several-fold increased. However, during stimulation with 27 mM glucose, secretion was inhibited by 30-50% and proinsulin biosynthesis by 30-40%. Total protein synthesis was similarly affected. Conversely, previous palmitate did not impair alpha-ketoisocaproic acid (5 mM)-induced insulin release. Induction and reversibility of the inhibitory effect on glucose-induced insulin secretion required between 6 and 24 h. Addition of the carnitine palmitoyltransferase I inhibitor etomoxir (1 microM) partially reversed (by > 50%) FFA-associated decrease in secretory as well as proinsulin biosynthetic responses to 27 mM glucose. The inhibitory effect of previous palmitate was similar when co-culture was performed with 5.5, 11, or 27 mM glucose. Exposure to palmitate or oleate reduced the production of 14CO2 from D-[U-14C]glucose, and of 14CO2 from D-[3,4-14C]-glucose, both effects being reversed by etomoxir. Conclusions: long-term exposure to FFA inhibits glucose-induced insulin secretion and biosynthesis probably through a glucose fatty acid cycle. PMID:8113418

Millennial and Non-Millennial Agriculture Teachers' Current and Ideal Emphasis on the Three Components of the Agricultural Education Program

ERIC Educational Resources Information Center

Shoulders, Catherine W.; Toland, Hannah

2017-01-01

Classroom and laboratory instruction, FFA, and SAE have long represented the complete agricultural education program via the three-component model. While the model depicts three circles of equal size to represent these components, the focus and level of emphasis of each component within the agriculture program is the decision of the agriculture…

Simultaneous conversion of free fatty acids and triglycerides to biodiesel by immobilized Aspergillus oryzae expressing Fusarium heterosporum lipase.

PubMed

Amoah, Jerome; Quayson, Emmanuel; Hama, Shinji; Yoshida, Ayumi; Hasunuma, Tomohisa; Ogino, Chiaki; Kondo, Akihiko

2017-03-01

The presence of high levels of free fatty acids (FFA) in oil is a barrier to one-step biodiesel production. Undesirable soaps are formed during conventional chemical methods, and enzyme deactivation occurs when enzymatic methods are used. This work investigates an efficient technique to simultaneously convert a mixture of free fatty acids and triglycerides (TAG). A partial soybean hydrolysate containing 73.04% free fatty acids and 24.81% triglycerides was used as a substrate for the enzymatic production of fatty acid methyl ester (FAME). Whole-cell Candida antarctica lipase B-expressing Aspergillus oryzae, and Novozym 435 produced only 75.2 and 73.5% FAME, respectively. Fusarium heterosporum lipase-expressing A. oryzae produced more than 93% FAME in 72 h using three molar equivalents of methanol. FFA and TAG were converted simultaneously in the presence of increasing water content that resulted from esterification. Therefore, F. heterosporum lipase with a noted high level of tolerance of water could be useful in the industrial production of biodiesel from feedstock that has high proportion of free fatty acids. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethanesulfonic acid-based esterification of industrial acidic crude palm oil for biodiesel production.

PubMed

Hayyan, Adeeb; Mjalli, Farouq S; Hashim, Mohd Ali; Hayyan, Maan; AlNashef, Inas M; Al-Zahrani, Saeed M; Al-Saadi, Mohammed A

2011-10-01

An industrial grade acidic crude palm oil (ACPO) pre-treatment process was carried out using ethanesulfonic acid (ESA) as a catalyst in the esterification reaction. ESA was used in different dosages to reduce free fatty acid (FFA) to a minimum level for the second stage of biodiesel production via alkaline transesterification reaction. Different process operating conditions were optimized such as ESA dosage (0.25-3.5% wt/wt), methanol to ACPO molar ratio (1:1-20:1), reaction temperature (40-70 °C), and reaction time (3-150 min). This study revealed the potential use of abundant quantities of ACPO from oil palm mills for biodiesel production. The lab scale results showed the effectiveness of the pre-treatment process using ESA catalyst. Three consecutive catalyst recycling runs were achieved without significant degradation in its performance. Second and third reuse runs needed more reaction time to achieve the target level of FFA content. Esterification and transesterification using ESA and KOH respectively is proposed for biodiesel industrial scale production. The produced biodiesel meets the international standards specifications for biodiesel fuel (EN 14214 and ASTM D6751). Copyright © 2011 Elsevier Ltd. All rights reserved.

A resolution commemorating 40 years of membership by women in the National FFA Organization and celebrating the achievements and contributions of female members of the National FFA Organization.

THOMAS, 111th Congress

Sen. Johanns, Mike [R-NE

2009-10-21

Senate - 10/21/2009 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (All Actions) Tracker: This bill has the status Agreed to in SenateHere are the steps for Status of Legislation:

A support vector regression-firefly algorithm-based model for limiting velocity prediction in sewer pipes.

PubMed

Ebtehaj, Isa; Bonakdari, Hossein

2016-01-01

Sediment transport without deposition is an essential consideration in the optimum design of sewer pipes. In this study, a novel method based on a combination of support vector regression (SVR) and the firefly algorithm (FFA) is proposed to predict the minimum velocity required to avoid sediment settling in pipe channels, which is expressed as the densimetric Froude number (Fr). The efficiency of support vector machine (SVM) models depends on the suitable selection of SVM parameters. In this particular study, FFA is used by determining these SVM parameters. The actual effective parameters on Fr calculation are generally identified by employing dimensional analysis. The different dimensionless variables along with the models are introduced. The best performance is attributed to the model that employs the sediment volumetric concentration (C(V)), ratio of relative median diameter of particles to hydraulic radius (d/R), dimensionless particle number (D(gr)) and overall sediment friction factor (λ(s)) parameters to estimate Fr. The performance of the SVR-FFA model is compared with genetic programming, artificial neural network and existing regression-based equations. The results indicate the superior performance of SVR-FFA (mean absolute percentage error = 2.123%; root mean square error =0.116) compared with other methods.

Removal of Free Fatty Acid from Plant Oil by the Adsorption Process

NASA Astrophysics Data System (ADS)

Chung, Tsair-Wang; Wu, Yi-Ling; Hsu, Shih-Hong

2018-05-01

The food oil refinery process for deacidification is ususally conducted by the neutralization after degumming. In this study, commercialized resins will be used as adsorbents to remove the free fatty acid (FFA) in food oil without using any solvent. Applying this environmental friendly green process, the energy efficiency will be increased and the waste water will be reduced compared to the traditional process. The selected adsorbent can be reused which may reduce the process cost. Instead of using alkali neutralization, the proposed process may reduce the concern of food oil security. The commercial resins A26OH and IRA900Cl were compared as adsorbents to remove the FFA in deacidification for refinery of food oil without adding any alkali chemicals. This process will be conducted to remove the FFA form peanut oil in this study. Besides, this study will get the adsorption isotherms for one of the better sorbents of A26OH or IRA900Cl to remove FFA from peanut oil under 25, 35, and 45°C. The Langmuir and Freundlich isotherm models were compared to fit the experimental data. The obtained isotherm data is important for the adsorption system design.

Facial color processing in the face-selective regions: an fMRI study.

PubMed

Nakajima, Kae; Minami, Tetsuto; Tanabe, Hiroki C; Sadato, Norihiro; Nakauchi, Shigeki

2014-09-01

Facial color is important information for social communication as it provides important clues to recognize a person's emotion and health condition. Our previous EEG study suggested that N170 at the left occipito-temporal site is related to facial color processing (Nakajima et al., [2012]: Neuropsychologia 50:2499-2505). However, because of the low spatial resolution of EEG experiment, the brain region is involved in facial color processing remains controversial. In the present study, we examined the neural substrates of facial color processing using functional magnetic resonance imaging (fMRI). We measured brain activity from 25 subjects during the presentation of natural- and bluish-colored face and their scrambled images. The bilateral fusiform face (FFA) area and occipital face area (OFA) were localized by the contrast of natural-colored faces versus natural-colored scrambled images. Moreover, region of interest (ROI) analysis showed that the left FFA was sensitive to facial color, whereas the right FFA and the right and left OFA were insensitive to facial color. In combination with our previous EEG results, these data suggest that the left FFA may play an important role in facial color processing. Copyright © 2014 Wiley Periodicals, Inc.

Decreasing high postprandial stearic acid in impaired fasting glucose by dietary regulation.

PubMed

Liu, L; Chu, X; Na, L; Yuan, F; Li, Y; Sun, C

2016-07-01

The objective of this study was to determine the postprandial change in free fatty acid (FFA) profiles in subjects with impaired fasting glucose (IFG), and to evaluate the effect of low glycemic index (GI) load on postprandial FFA profiles and inflammation. First, 50 IFG and 50 healthy subjects were recruited; and 2 -h postprandial changes in FFA profiles were determined. Second, the 50 IFG subjects then received three different loads: glucose load (GL), high glycemic index (HGI) load and low glycemic index (LGI) load, respectively. FFA profile, glucose, insulin, glucagon-like peptide 1 (GLP-1) and inflammatory biomarkers were assayed at 0, 30, 60, 90 and 120 min. Postprandial stearic acid (C18:0) increased compared with baseline in all subjects, whereas the change in postprandial C18:0 was more marked in IFG subjects than in healthy subjects. Compared with subjects who received the GL and HGI load, the area under the curve for insulin, GLP-1, C18:0 and tumor necrosis factor-alpha significantly decreased and adiponectin increased in subjects who received the LGI load. The rise in postprandial C18:0 in IFG subjects was inhibited by LGI load.

Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups.

PubMed

Punyadeera, C; van der Merwe, M T; Crowther, N J; Toman, M; Immelman, A R; Schlaphoff, G P; Gray, I P

2001-08-01

The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. Anthropometric and various metabolic indices were measured at fasting and during a 7 h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. Visceral fat levels were significantly higher (P<0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P<0.05 for both) and was found to correlate negatively with weight (r=-0.69, P<0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OGTT was 24+/-12% in OWW and -38+/-23% (P<0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120--420 min) was significantly higher in OWW than OBW (P<0.01) and LWW (P<0.01) and correlated positively with visceral fat mass independent of age (r=0.78, P<0.05) in the OWW only. Leptin levels were higher (P<0.01) both at fasting and during the course of the OGTT in obese women from both ethnic groups compared to the lean women. Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Does sterilization with fractionated electron beam irradiation prevent ACL tendon allograft from tissue damage?

PubMed

Schmidt, T; Grabau, D; Grotewohl, J H; Gohs, U; Pruß, A; Smith, M; Scheffler, S; Hoburg, A

2017-02-01

Allografts are frequently used for anterior cruciate ligament (ACL) reconstruction. However, due to the inherent risk of infection, a method that achieves complete sterilization of grafts is warranted without impairing their biomechanical properties. Fractionation of electron beam (FEbeam) irradiation has been shown to maintain similar biomechanical properties compared to fresh-frozen allografts (FFA) in vitro. Therefore, aim of this study was to evaluate the biomechanical properties and early remodelling of grafts that were sterilized with fractionated high-dose electron beam irradiation in an in vivo sheep model. ACL reconstruction was performed in 18 mature merino mix sheep. Sixteen were reconstructed with allografts sterilized with FEbeam irradiation (8 × 3.4 kGy) and two with FFA. Eight FFA from prior studies with identical surgical reconstruction and biomechanical and histological analyzes served as controls. Half of the animals were sacrificed at 6 and 12 weeks, and biomechanical testing was performed. Anterior-posterior laxity (APL) was assessed with an AP drawer test at 60° flexion, and load to failure testing was carried out. Histological evaluation of mid-substance samples was performed for descriptive analysis, cell count, crimp and vessel density. For statistical analysis a Kruskal-Wallis test was used for overall group comparison followed by a Mann-Whitney U test for pairwise comparison of the histological and biomechanical parameters. Biomechanical testing showed significantly decreased stiffness in FEbeam compared to FFA at both time points (p ≤ 0.004). APL was increased in FEbeam compared to FFA, which was significant at 6 weeks (p = 0.004). Median of failure loads was decreased in FEbeam grafts, with 12 reconstructions already failing during cyclic loading. Vessel density was decreased in FEbeam compared to FFA at both time points, with significant differences at 12 weeks (p = 0.015). Crimp length was significantly shorter in FEbeam compared to FFA at both time points (p ≤ 0.004) and decreased significantly in both groups from 6 to 12 weeks (p ≤ 0.025). ACL reconstruction with fractionated Ebeam sterilization significantly alters the biomechanical properties and the early remodelling process of treated grafts in vivo. Therefore, this sterilization method cannot be recommended for clinical application. As substantial changes in the remodelling are inherent in this study, care in the rehabilitation of even low-dose sterilized allografts, used for ACL reconstruction, is recommended.

Using Agriculture to Make a Difference

ERIC Educational Resources Information Center

Kidwai, Sabrina

2011-01-01

Growing up in Philadelphia, Jenna Moser always wanted to be like her dad, who was a member of FFA and grew up on a farm in western Pennsylvania. She took a big step in emulating her father when she enrolled at the W. B. Saul High School of Agricultural Sciences, and became a member of FFA herself, going on to serve as president during her senior…

A Quantitative and Standardized Method for the Evaluation of Choroidal Neovascularization Using MICRON III Fluorescein Angiograms in Rats

PubMed Central

Wigg, Jonathan P.; Zhang, Hong; Yang, Dong

2015-01-01

Introduction In-vivo imaging of choroidal neovascularization (CNV) has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD) in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch’s membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA) image analysis for CNV lesions. Methods Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories) over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated. Results CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p<0.001) and fluorescent intensity (p<0.001) than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p<0.001) in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049) and 3 weeks (p<0.001) post laser. Conclusion The presented method of in-vivo FFA quantification of CNV, including acquisition variable corrections, using the Micron III system and common use software establishes a reliable method for detecting and quantifying CNV enabling longitudinal studies and represents an important alternative to conventional CNV quantification methods. PMID:26024231

Broadband Spectral Modeling of the Extreme Gigahertz-peaked Spectrum Radio Source PKS B0008-421

NASA Astrophysics Data System (ADS)

Callingham, J. R.; Gaensler, B. M.; Ekers, R. D.; Tingay, S. J.; Wayth, R. B.; Morgan, J.; Bernardi, G.; Bell, M. E.; Bhat, R.; Bowman, J. D.; Briggs, F.; Cappallo, R. J.; Deshpande, A. A.; Ewall-Wice, A.; Feng, L.; Greenhill, L. J.; Hazelton, B. J.; Hindson, L.; Hurley-Walker, N.; Jacobs, D. C.; Johnston-Hollitt, M.; Kaplan, D. L.; Kudrayvtseva, N.; Lenc, E.; Lonsdale, C. J.; McKinley, B.; McWhirter, S. R.; Mitchell, D. A.; Morales, M. F.; Morgan, E.; Oberoi, D.; Offringa, A. R.; Ord, S. M.; Pindor, B.; Prabu, T.; Procopio, P.; Riding, J.; Srivani, K. S.; Subrahmanyan, R.; Udaya Shankar, N.; Webster, R. L.; Williams, A.; Williams, C. L.

2015-08-01

We present broadband observations and spectral modeling of PKS B0008-421 and identify it as an extreme gigahertz-peaked spectrum (GPS) source. PKS B0008-421 is characterized by the steepest known spectral slope below the turnover, close to the theoretical limit of synchrotron self-absorption, and the smallest known spectral width of any GPS source. Spectral coverage of the source spans from 0.118 to 22 GHz, which includes data from the Murchison Widefield Array and the wide bandpass receivers on the Australia Telescope Compact Array. We have implemented a Bayesian inference model fitting routine to fit the data with internal free-free absorption (FFA), single- and double-component FFA in an external homogeneous medium, FFA in an external inhomogeneous medium, or single- and double-component synchrotron self-absorption models, all with and without a high-frequency exponential break. We find that without the inclusion of a high-frequency break these models cannot accurately fit the data, with significant deviations above and below the peak in the radio spectrum. The addition of a high-frequency break provides acceptable spectral fits for the inhomogeneous FFA and double-component synchrotron self-absorption models, with the inhomogeneous FFA model statistically favored. The requirement of a high-frequency spectral break implies that the source has ceased injecting fresh particles. Additional support for the inhomogeneous FFA model as being responsible for the turnover in the spectrum is given by the consistency between the physical parameters derived from the model fit and the implications of the exponential spectral break, such as the necessity of the source being surrounded by a dense ambient medium to maintain the peak frequency near the gigahertz region. This implies that PKS B0008-421 should display an internal H i column density greater than 1020 cm-2. The discovery of PKS B0008-421 suggests that the next generation of low radio frequency surveys could reveal a large population of GPS sources that have ceased activity, and that a portion of the ultra-steep-spectrum source population could be composed of these GPS sources in a relic phase.

Marginal Vitamin B-6 Deficiency Decreases Plasma (n-3) and (n-6) PUFA Concentrations in Healthy Men and Women123

PubMed Central

Zhao, Mei; Lamers, Yvonne; Ralat, Maria A.; Coats, Bonnie S.; Chi, Yueh-Yun; Muller, Keith E.; Bain, James R.; Shankar, Meena N.; Newgard, Christopher B.; Stacpoole, Peter W.; Gregory, Jesse F.

2012-01-01

Previous animal studies showed that severe vitamin B-6 deficiency altered fatty acid profiles of tissue lipids, often with an increase of linoleic acid and a decrease of arachidonic acid. However, little is known about the extent to which vitamin B-6 deficiency affects human fatty acid profiles. The aim of this study was to determine the effects of marginal vitamin B-6 deficiency on fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy adults fed a 28-d, low-vitamin B-6 diet. Healthy participants (n = 23) received a 2-d, controlled, vitamin B-6–adequate diet followed by a 28-d, vitamin B-6–restricted diet to induce a marginal deficiency. Plasma HDL and LDL cholesterol concentrations, FFA concentrations, and erythrocyte and PBMC membrane fatty acid compositions did not significantly change from baseline after the 28-d restriction. Plasma total arachidonic acid, EPA, and DHA concentrations decreased from (mean ± SD) 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L [positive false discovery rate (pFDR) adjusted P < 0.05], respectively. The total (n-6):(n-3) PUFA ratio in plasma exhibited a minor increase from 15.4 ± 2.8 to 16.6 ± 3.1 (pFDR adjusted P < 0.05). These data indicate that short-term vitamin B-6 restriction decreases plasma (n-3) and (n-6) PUFA concentrations and tends to increase the plasma (n-6):(n-3) PUFA ratio. Such changes in blood lipids may be associated with the elevated risk of cardiovascular disease in vitamin B-6 insufficiency. PMID:22955512

Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo

PubMed Central

Liu, Zhengtao; Chen, Tianchi; Lu, Xiaoxiao; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

2016-01-01

Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3WT) and mutant 148M (PNPLA3I148M), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3I148M on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3I148M in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3I148M cells via upregulation of interleukin-6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3I148M cells incubated in low-dose FFA. In low oxidative stress, PNPLA3I148M initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3I148M cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant. PMID:27186262

Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo.

PubMed

Liu, Zhengtao; Chen, Tianchi; Lu, Xiaoxiao; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

2016-01-01

Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3(WT)) and mutant 148M (PNPLA3(I148M)), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3(I148M) on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3(I148M) in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (P<0.05). Low-dose FFA specifically activated JAK2/STAT3 phosphorylation of PNPLA3(I148M) cells via upregulation of interleukin-6. Animal study showed high-fat diet accelerated growth of xenografts derived from PNPLA3(I148M) cells incubated in low-dose FFA. In low oxidative stress, PNPLA3(I148M) initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3(I148M) cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant.

Expanding the spectrum of frontal fibrosing alopecia: a unifying concept.

PubMed

Chew, Ai-Lean; Bashir, Saqib J; Wain, E Mary; Fenton, David A; Stefanato, Catherine M

2010-10-01

In frontal fibrosing alopecia (FFA), scalp alopecia dominates the clinical picture. However, eyebrow loss and hair loss in other body sites may also occur; this has been documented clinically, but rarely histopathologically. We describe the clinicopathological findings of 13 cases of FFA, with histopathologic data from the scalp, eyebrow, and body hair. Thirteen patients with a diagnosis of FFA, seen between 2006 and 2008, were included. Scalp biopsies were performed in all patients for histology and direct immunofluorescence (DIF). Biopsy specimens for histology were taken from the eyebrow in 6 patients and from the upper limb in 5 patients. All 13 patients were female, 11 of whom were postmenopausal. The median age at onset of alopecia was 57 years. Clinical examination revealed a band of frontal hairline recession in all patients. Eyebrow loss was present clinically in all patients, with loss of body hair in 10 of 13. Histopathologic examination of the scalp, eyebrow, and upper limb skin biopsy specimens showed similar features, including a marked reduction in the number of hair follicles and a perifollicular lymphoid cell infiltrate with perifollicular fibrosis. Direct immunofluorescence was negative in all cases. Not all patients consented to biopsies of the eyebrows or upper limbs. Eyebrow and peripheral body hair loss is not uncommon in FFA-a finding that is likely underreported. We have demonstrated that alopecia of the upper limbs in FFA is indeed common and, histopathologically, shows features of lichen planopilaris and scarring, similar to findings in the scalp and eyebrows. Consequently, the process of lichen planopilaris with scarring alopecia is generalized rather than localized only to the frontal scalp and eyebrows.

Design, Implementation, and Wide Pilot Deployment of FitForAll: An Easy to use Exergaming Platform Improving Physical Fitness and Life Quality of Senior Citizens.

PubMed

Konstantinidis, Evdokimos I; Billis, Antonis S; Mouzakidis, Christos A; Zilidou, Vasiliki I; Antoniou, Panagiotis E; Bamidis, Panagiotis D

2016-01-01

Many platforms have emerged as response to the call for technology supporting active and healthy aging. Key requirements for any such e-health systems and any subsequent business exploitation are tailor-made design and proper evaluation. This paper presents the design, implementation, wide deployment, and evaluation of the low cost, physical exercise, and gaming (exergaming) FitForAll (FFA) platform system usability, user adherence to exercise, and efficacy are explored. The design of FFA is tailored to elderly populations, distilling literature guidelines and recommendations. The FFA architecture introduces standard physical exercise protocols in exergaming software engineering, as well as, standard physical assessment tests for augmented adaptability through adjustable exercise intensity. This opens up the way to next generation exergaming software, which may be more automatically/smartly adaptive. 116 elderly users piloted FFA five times/week, during an eight-week controlled intervention. Usability evaluation was formally conducted (SUS, SUMI questionnaires). Control group consisted of a size-matched elderly group following cognitive training. Efficacy was assessed objectively through the senior fitness (Fullerton) test, and subjectively, through WHOQoL-BREF comparisons of pre-postintervention between groups. Adherence to schedule was measured by attendance logs. The global SUMI score was 68.33±5.85%, while SUS was 77.7. Good usability perception is reflected in relatively high adherence of 82% for a daily two months pilot schedule. Compared to control group, elderly using FFA improved significantly strength, flexibility, endurance, and balance while presenting a significant trend in quality of life improvements. This is the first elderly focused exergaming platform intensively evaluated with more than 100 participants. The use of formal tools makes the findings comparable to other studies and forms an elderly exergaming corpus.

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma.

PubMed

O'Byrne, Paul M; Jacques, Loretta; Goldfrad, Caroline; Kwon, Namhee; Perrio, Michael; Yates, Louisa J; Busse, William W

2016-11-24

Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients. Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma. Safety data from 10 parallel-group, randomised, double-blind Phase II and III studies (including 3345 patients who received at least one dose of fluticasone furoate) were integrated to provide information on adverse events, withdrawals, laboratory assessments, vital signs and hypothalamic-pituitary-adrenal axis function. The efficacy of once-daily fluticasone furoate was evaluated in all included studies. Once-daily fluticasone furoate 100 μg and 200 μg safety profiles were consistent with those reported for other inhaled corticosteroids, and both doses consistently demonstrated efficacy versus placebo. In the integrated analysis, no dose-response relationship was observed for the overall incidence of adverse events and there were no significant effects of fluticasone furoate on hypothalamic-pituitary-adrenal axis function. Once-daily fluticasone furoate 100 μg and 200 μg had acceptable safety profiles and was efficacious in adult and adolescent patients with asthma. There was no evidence of cortisol suppression at studied doses. GSK (NCT01499446/FFA20001, NCT00398645/FFA106783, NCT00766090/112202, NCT00603746/FFA109684, NCT00603278/FFA109685, NCT00603382/FFA109687, NCT01436071/115283, NCT01436110/115285, NCT01159912/112059, NCT01431950/114496, NCT01165138/HZA106827, NCT01086384/106837, NCT01134042/HZA106829 and NCT01244984/1139879).

The acute effects of inulin and resistant-starch on postprandial serum short-chain fatty acids and second-meal glycaemic response in lean and overweight humans

PubMed Central

Rahat-Rozenbloom, Sari; Fernandes, Judlyn; Cheng, Ji; Gloor, Gregory B; Wolever, Thomas MS

2016-01-01

Background/Objectives Colonic-fermentation of dietary-fibre to short-chain fatty-acids (SCFA) may protect against obesity and diabetes, but excess production of colonic SCFA has been implicated in the promotion of obesity. We aimed to compare the effects of two fermentable-fibres on postprandial SCFA and second-meal glycaemic response in healthy overweight or obese (OWO) vs lean (LN) participants. Methods using a randomized cross-over design, 13 OWO and 12 LN overnight fasted participants were studied for 6h on 3 separate days after consuming 300mL water containing 75g glucose(GLU) as control or with 24g inulin(IN) or 28g resistant-starch(RS). A standard lunch was served 4h after the test-drink. Results Within the entire group, compared to control, IN significantly increased serum SCFA (p<0.001) but had no effect on FFA or second-meal glucose and insulin responses. In contrast, RS had no significant effect on SCFA but reduced FFA rebound (p<0.001) and second-meal glucose (p=0.002) and insulin responses (p=0.024). OWO had similar postprandial serum SCFA and glucose concentrations but significantly greater insulin and FFA than LN. However, the effects of IN and RS on SCFA, glucose, insulin and FFA responses were similar in LN and OWO. Conclusions Resistant-starch has favorable second-meal effects, likely related to changes in FFA rather than SCFA concentrations. However, a longer study may be needed to demonstrate an effect of RS on SCFA. We found no evidence that acute increases in SCFA after IN reduce glycaemic responses in humans, and we were unable to detect a significant difference in SCFA responses between OWO vs LN subjects. PMID:27966565

Metabolic fate of glucose and candidate signaling and excess-fuel detoxification pathways in pancreatic β-cells.

PubMed

Mugabo, Yves; Zhao, Shangang; Lamontagne, Julien; Al-Mass, Anfal; Peyot, Marie-Line; Corkey, Barbara E; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

2017-05-05

Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mm glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mm glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose-dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS-1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to triglycerides and cholesterol esters. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Intravenous Lipid Infusion Induces Endoplasmic Reticulum Stress in Endothelial Cells and Blood Mononuclear Cells of Healthy Adults.

PubMed

Tampakakis, Emmanouil; Tabit, Corey E; Holbrook, Monika; Linder, Erika A; Berk, Brittany D; Frame, Alissa A; Bretón-Romero, Rosa; Fetterman, Jessica L; Gokce, Noyan; Vita, Joseph A; Hamburg, Naomi M

2016-01-11

Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response may initially be protective, but when prolonged, have been implicated in atherogenesis in diabetic conditions. Triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to ER stress. We sought to evaluate the effect of acute FFA elevation on ER stress in endothelial and circulating white cells. Twenty-one healthy subjects were treated with intralipid (20%; 45 mL/h) plus heparin (12 U/kg/h) infusion for 5 hours. Along with increased triglyceride and FFA levels, intralipid/heparin infusion reduced the calf reactive hyperemic response without a change in conduit artery flow-mediated dilation consistent with microvascular dysfunction. To investigate the short-term effects of elevated triglycerides and FFA, we measured markers of ER stress in peripheral blood mononuclear cells (PBMCs) and vascular endothelial cells (VECs). In VECs, activating transcription factor 6 (ATF6) and phospho-inositol requiring kinase 1 (pIRE1) proteins were elevated after infusion (both P<0.05). In PBMCs, ATF6 and spliced X-box-binding protein 1 (XBP-1) gene expression increased by 2.0- and 2.5-fold, respectively (both P<0.05), whereas CHOP and GADD34 decreased by ≈67% and 74%, respectively (both P<0.01). ATF6 and pIRE1 protein levels also increased (both P<0.05), and confocal microscopy revealed the nuclear localization of ATF6 after infusion, suggesting activation. Along with microvascular dysfunction, intralipid infusion induced an early protective ER stress response evidenced by activation of ATF6 and IRE1 in both leukocytes and endothelial cells. Our results suggest a potential link between metabolic disturbances and ER stress that may be relevant to vascular disease. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Fatty Acid Oxidation Changes and the Correlation with Oxidative Stress in Different Preeclampsia-Like Mouse Models

PubMed Central

Ding, Xiaoyan; Yang, Zi; Han, Yiwei; Yu, Huan

2014-01-01

Background Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway. Methods PE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) and the antiphospholipid syndrome (APS) mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups). The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre) and mid-pregnancy (Mid) subgroups by injection time. Results All PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05). LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05) but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups. Conclusions Abnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway. PMID:25302499

Seeing Jesus in toast: neural and behavioral correlates of face pareidolia.

PubMed

Liu, Jiangang; Li, Jun; Feng, Lu; Li, Ling; Tian, Jie; Lee, Kang

2014-04-01

Face pareidolia is the illusory perception of non-existent faces. The present study, for the first time, contrasted behavioral and neural responses of face pareidolia with those of letter pareidolia to explore face-specific behavioral and neural responses during illusory face processing. Participants were shown pure-noise images but were led to believe that 50% of them contained either faces or letters; they reported seeing faces or letters illusorily 34% and 38% of the time, respectively. The right fusiform face area (rFFA) showed a specific response when participants "saw" faces as opposed to letters in the pure-noise images. Behavioral responses during face pareidolia produced a classification image (CI) that resembled a face, whereas those during letter pareidolia produced a CI that was letter-like. Further, the extent to which such behavioral CIs resembled faces was directly related to the level of face-specific activations in the rFFA. This finding suggests that the rFFA plays a specific role not only in processing of real faces but also in illusory face perception, perhaps serving to facilitate the interaction between bottom-up information from the primary visual cortex and top-down signals from the prefrontal cortex (PFC). Whole brain analyses revealed a network specialized in face pareidolia, including both the frontal and occipitotemporal regions. Our findings suggest that human face processing has a strong top-down component whereby sensory input with even the slightest suggestion of a face can result in the interpretation of a face. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beyond the FFA: The Role of the Ventral Anterior Temporal Lobes in Face Processing

PubMed Central

Collins, Jessica A.; Olson, Ingrid R.

2014-01-01

Extensive research has supported the existence of a specialized face-processing network that is distinct from the visual processing areas used for general object recognition. The majority of this work has been aimed at characterizing the response properties of the fusiform face area (FFA) and the occipital face area (OFA), which together are thought to constitute the core network of brain areas responsible for facial identification. Although accruing evidence has shown that face-selective patches in the ventral anterior temporal lobes (vATLs) are interconnected with the FFA and OFA, and that they play a role in facial identification, the relative contribution of these brain areas to the core face-processing network has remained unarticulated. Here we review recent research critically implicating the vATLs in face perception and memory. We propose that current models of face processing should be revised such that the ventral anterior temporal lobes serve a centralized role in the visual face-processing network. We speculate that a hierarchically organized system of face processing areas extends bilaterally from the inferior occipital gyri to the vATLs, with facial representations becoming increasingly complex and abstracted from low-level perceptual features as they move forward along this network. The anterior temporal face areas may serve as the apex of this hierarchy, instantiating the final stages of face recognition. We further argue that the anterior temporal face areas are ideally suited to serve as an interface between face perception and face memory, linking perceptual representations of individual identity with person-specific semantic knowledge. PMID:24937188

The short-chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis.

PubMed

Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M; Angueira, Anthony R; Brodsky, Michael; Hayes, M Geoffrey; Kovatcheva-Datchary, Petia; Bäckhed, Fredrik; Gilbert, Jack A; Lowe, William L; Layden, Brian T

2015-11-15

The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene (Ffar2) expression is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Together, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome.

PubMed

Lucero, Diego; Zago, Valeria; López, Graciela I; Graffigna, Mabel; Fainboim, Hugo; Miksztowicz, Verónica; Meroño, Tomás; Belli, Susana; Levalle, Oscar; Wikinski, Regina; Brites, Fernando; Berg, Gabriela; Schreier, Laura

2011-01-14

It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = -0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = -0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition. Copyright © 2010 Elsevier B.V. All rights reserved.

Differences in neural responses to ipsilateral stimuli in wide-view fields between face- and house-selective areas

PubMed Central

Li, Ting; Niu, Yan; Xiang, Jie; Cheng, Junjie; Liu, Bo; Zhang, Hui; Yan, Tianyi; Kanazawa, Susumu; Wu, Jinglong

2018-01-01

Category-selective brain areas exhibit varying levels of neural activity to ipsilaterally presented stimuli. However, in face- and house-selective areas, the neural responses evoked by ipsilateral stimuli in the peripheral visual field remain unclear. In this study, we displayed face and house images using a wide-view visual presentation system while performing functional magnetic resonance imaging (fMRI). The face-selective areas (fusiform face area (FFA) and occipital face area (OFA)) exhibited intense neural responses to ipsilaterally presented images, whereas the house-selective areas (parahippocampal place area (PPA) and transverse occipital sulcus (TOS)) exhibited substantially smaller and even negative neural responses to the ipsilaterally presented images. We also found that the category preferences of the contralateral and ipsilateral neural responses were similar. Interestingly, the face- and house-selective areas exhibited neural responses to ipsilateral images that were smaller than the responses to the contralateral images. Multi-voxel pattern analysis (MVPA) was implemented to evaluate the difference between the contralateral and ipsilateral responses. The classification accuracies were much greater than those expected by chance. The classification accuracies in the FFA were smaller than those in the PPA and TOS. The closer eccentricities elicited greater classification accuracies in the PPA and TOS. We propose that these ipsilateral neural responses might be interpreted by interhemispheric communication through intrahemispheric connectivity of white matter connection and interhemispheric connectivity via the corpus callosum and occipital white matter connection. Furthermore, the PPA and TOS likely have weaker interhemispheric communication than the FFA and OFA, particularly in the peripheral visual field. PMID:29451872

Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway.

PubMed

Chen, Qian; Liu, Mengyang; Yu, Haiyang; Li, Jian; Wang, Sijian; Zhang, Yi; Qiu, Feng; Wang, Tao

2018-06-01

Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-A y mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-A y mice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element binding protein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyl transferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.

Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease

PubMed Central

2012-01-01

Background In vitro exposure of liver cells to high concentrations of free fatty acids (FFA) results in fat overload which promotes inflammatory and fibrogenic response similar to those observed in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH). Since the mechanisms of this event have not been fully characterized, we aimed to analyze the fibrogenic stimuli in a new in vitro model of NASH. Methods HuH7 cells were cultured for 24 h in an enriched medium containing bovine serum albumin and increasing concentrations of palmitic and oleic acid at a molar ratio of 1:2 (palmitic and oleic acid, respectively). Cytotoxic effect, apoptosis, oxidative stress, and production of inflammatory and fibrogenic cytokines were measured. Results FFA induces a significant increment in the intracellular content of lipid droplets. The gene expression of interleukin-6, interleukin-8 and tumor necrosis factor alpha was significantly increased. The protein level of interleukin-8 was also increased. Intracellular lipid accumulation was associated to a significant up-regulation in the gene expression of transforming growth factor beta 1, alpha 2 macroglobulin, vascular endothelial growth factor A, connective tissue growth factor, insulin-like growth factor 2, thrombospondin 1. Flow cytometry analysis demonstrated a significant increment of early apoptosis and production of reactive oxygen species. Conclusions The exposure of hepatocytes to fatty acids elicits inflammation, increase of oxidative stress, apoptosis and production of fibrogenic cytokines. These data support a primary role of FFA in the pathogenesis of NAFLD and NASH. PMID:22380754

The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity.

PubMed

Doseyici, S; Mehmetoglu, I; Toker, A; Yerlikaya, F H; Erbay, E

2014-07-01

Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.

Extension of classical hydrological risk analysis to non-stationary conditions due to climate change - application to the Fulda catchment, Germany

NASA Astrophysics Data System (ADS)

Fink, G.; Koch, M.

2010-12-01

An important aspect in water resources and hydrological engineering is the assessment of hydrological risk, due to the occurrence of extreme events, e.g. droughts or floods. When dealing with the latter - as is the focus here - the classical methods of flood frequency analysis (FFA) are usually being used for the proper dimensioning of a hydraulic structure, for the purpose of bringing down the flood risk to an acceptable level. FFA is based on extreme value statistics theory. Despite the progress of methods in this scientific branch, the development, decision, and fitting of an appropriate distribution function stills remains a challenge, particularly, when certain underlying assumptions of the theory are not met in real applications. This is, for example, the case when the stationarity-condition for a random flood time series is not satisfied anymore, as could be the situation when long-term hydrological impacts of future climate change are to be considered. The objective here is to verify the applicability of classical (stationary) FFA to predicted flood time series in the Fulda catchment in central Germany, as they may occur in the wake of climate change during the 21st century. These discharge time series at the outlet of the Fulda basin have been simulated with a distributed hydrological model (SWAT) that is forced by predicted climate variables of a regional climate model for Germany (REMO). From the simulated future daily time series, annual maximum (extremes) values are computed and analyzed for the purpose of risk evaluation. Although the 21st century estimated extreme flood series of the Fulda river turn out to be only mildly non-stationary, alleviating the need for further action and concern at the first sight, the more detailed analysis of the risk, as quantified, for example, by the return period, shows non-negligent differences in the calculated risk levels. This could be verified by employing a new method, the so-called flood series maximum analysis (FSMA) method, which consists in the stochastic simulation of numerous trajectories of a stochastic process with a given GEV-distribution over a certain length of time (> larger than a desired return period). Then the maximum value for each trajectory is computed, all of which are then used to determine the empirical distribution of this maximum series. Through graphical inversion of this distribution function the size of the design flood for a given risk (quantile) and given life duration can be inferred. The results of numerous simulations show that for stationary flood series, the new FSMA method results, expectedly, in nearly identical risk values as the classical FFA approach. However, once the flood time series becomes slightly non-stationary - for reasons as discussed - and regardless of whether the trend is increasing or decreasing, large differences in the computed risk values for a given design flood occur. Or in other word, for the same risk, the new FSMA method would lead to different values in the design flood for a hydraulic structure than the classical FFA method. This, in turn, could lead to some cost savings in the realization of a hydraulic project.

Free fatty acid suppositories are as effective as docusate sodium and sorbitol enemas in treating constipation in children.

PubMed

Ormarsson, Orri Thor; Asgrimsdottir, Gudrun Marta; Loftsson, Thorsteinn; Stefansson, Einar; Lund, Sigrun Helga; Bjornsson, Einar Stefan

2016-06-01

A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Dynamic adjustments in prefrontal, hippocampal, and inferior temporal interactions with increasing visual working memory load.

PubMed

Rissman, Jesse; Gazzaley, Adam; D'Esposito, Mark

2008-07-01

The maintenance of visual stimuli across a delay interval in working memory tasks is thought to involve reverberant neural communication between the prefrontal cortex and posterior visual association areas. Recent studies suggest that the hippocampus might also contribute to this retention process, presumably via reciprocal interactions with visual regions. To characterize the nature of these interactions, we performed functional connectivity analysis on an event-related functional magnetic resonance imaging data set in which participants performed a delayed face recognition task. As the number of faces that participants were required to remember was parametrically increased, the right inferior frontal gyrus (IFG) showed a linearly decreasing degree of functional connectivity with the fusiform face area (FFA) during the delay period. In contrast, the hippocampus linearly increased its delay period connectivity with both the FFA and the IFG as the mnemonic load increased. Moreover, the degree to which participants' FFA showed a load-dependent increase in its connectivity with the hippocampus predicted the degree to which its connectivity with the IFG decreased with load. Thus, these neural circuits may dynamically trade off to accommodate the particular mnemonic demands of the task, with IFG-FFA interactions mediating maintenance at lower loads and hippocampal interactions supporting retention at higher loads.

Triglycerides produced in the livers of fasting rabbits are predominantly stored as opposed to secreted into the plasma

PubMed Central

Tuvdendorj, Demidmaa; Zhang, Xiao-jun; Chinkes, David L.; Wang, Lijian; Wu, Zhanpin; Rodriguez, Noe A.; Herndon, David N.; Wolfe, Robert R.

2015-01-01

Objective The liver plays a central role in regulating fat metabolism; however, it is not clear how the liver distributes the synthesized triglycerides (TGs) to storage and to the plasma. Materials and Methods We have measured the relative distribution of TGs produced in the liver to storage and the plasma by means of U-13C16-palmitate infusion in anesthetized rabbits after an overnight fast. Results The fractional synthesis rates of TGs stored in the liver and secreted into the plasma were not significantly different (Stored vs. Secreted: 31.9 ± 0.8 vs. 27.7 ± 2.6 %•h−1, p > 0.05. However, the absolute synthesis rates of hepatic stored and secreted TGs were 543 ± 158 and 27 ± 7 nmol·kg−1·min−1 respectively, indicating that in fasting rabbits the TGs produced in the liver were predominately stored (92±3%) rather than secreted (8±3%) into the plasma. This large difference was mainly due to the larger pool size of the hepatic TGs which was 21±9-fold that of plasma TGs. Plasma free fatty acids (FFAs) contributed 47±1% of the FA precursor for hepatic TG synthesis, and the remaining 53±1% was derived from hepatic lipid breakdown and possibly plasma TGs depending on the activity of hepatic lipase. Plasma palmitate concentration significantly correlated with hepatic palmitoyl-CoA and TG synthesis. Conclusion In rabbits, after an overnight fast, the absolute synthesis rate of hepatic stored TGs was significantly higher than that of secreted due to the larger pool size of hepatic TGs. The net synthesis rate of TG was approximately half the absolute rate. Plasma FFA is a major determinant of hepatic TG synthesis, and therefore hepatic TG storage. PMID:25682063

Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, R.R.; Shaw, J.H.; Durkot, M.J.

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with (2-/sup 3/H)glycerol and (1-/sup 14/C)palmitic acid, was used to trace VLDL kinetics and oxidation, and (1-/sup 13/C)palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an importantmore » contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. The authors conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.« less

Fatty acids trigger mitochondrion-dependent necrosis.

PubMed

Rockenfeller, Patrick; Ring, Julia; Muschett, Vera; Beranek, Andreas; Buettner, Sabrina; Carmona-Gutierrez, Didac; Eisenberg, Tobias; Khoury, Chamel; Rechberger, Gerald; Kohlwein, Sepp D; Kroemer, Guido; Madeo, Frank

2010-07-15

Obesity is characterised by lipid accumulation in non-adipose tissues, leading to organ degeneration and a wide range of diseases, including diabetes, heart attack and liver cirrhosis. Free fatty acids (FFA) are believed to be the principal toxic triggers mediating the adverse cellular effects of lipids. Here, we show that various cooking oils used in human nutrition cause cell death in yeast in the presence of a triacylglycerol lipase, mimicking the physiological microenvironment of the small intestine. Combining genetic and cell death assays, we demonstrate that elevated FFA concentrations lead to necrotic cell death, as evidenced by loss of membrane integrity and release of nuclear HMGB1. FFA-mediated necrosis depends on functional mitochondria and leads to the accumulation of reactive oxygen species. We conclude that lipotoxicity is executed via a mitochondrial necrotic pathway, challenging the dogma that the adverse effects of lipid stress are exclusively apoptotic.

A green recyclable SO(3)H-carbon catalyst derived from glycerol for the production of biodiesel from FFA-containing karanja (Pongamia glabra) oil in a single step.

PubMed

Prabhavathi Devi, B L A; Vijai Kumar Reddy, T; Vijaya Lakshmi, K; Prasad, R B N

2014-02-01

Simultaneous esterification and transesterification method is employed for the preparation of biodiesel from 7.5% free fatty acid (FFA) containing karanja (Pongamia glabra) oil using water resistant and reusable carbon-based solid acid catalyst derived from glycerol in a single step. The optimum reaction parameters for obtaining biodiesel in >99% yield by simultaneous esterification and transesterification are: methanol (1:45 mole ratio of oil), catalyst 20wt.% of oil, temperature 160°C and reaction time of 4h. After the reaction, the catalyst was easily recovered by filtration and reused for five times with out any deactivation under optimized conditions. This single-step process could be a potential route for biodiesel production from high FFA containing oils by simplifying the procedure and reducing costs and effluent generation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acidemia and blood free fatty acids: analysis of cardiovascular risk factors in a new context.

PubMed

Reis, António Heitor

2017-03-01

Following a hypothesis developed in an earlier paper, here it is discussed how deviations of blood pH from the normal range (namely states of acidemia) together with high blood levels of free fatty acids (FFA) may offer a rationale for many important risk factors for cardiovascular diseases (CVD) by shaping a context for formation of fatty acid micelles and vesicles with an acidic core, which fuse with the endothelia, disrupt vital cell processes, and thereby may initiate atherosclerotic plaque formation. Acidemia may arise primarily from dysregulation of the systemic buffers that control blood pH, chronic diseases of kidneys and lungs, inappropriate diet, or may be induced by some common drugs. The level of free fatty acids may be increased and maintained high by chronic stress, and adrenergic shocks. Elevated concentrations of blood FFA in a context of acidemia allow to understand important cardiovascular aspects: the increased risk of menopausal women, the protective effects of physical exercise, the changes in vascular behavior characteristic of metabolic acidosis/acidemia, the role of diet in the pH balance, on how some known medicines like metformin, steroids, NSAIDS, proton pump inhibitors, and calcium supplements may influence CVD risk, and an explanation is offered for the role of statins.

Adipose Triglyceride Lipase Is Implicated in Fuel- and Non-fuel-stimulated Insulin Secretion*

PubMed Central

Peyot, Marie-Line; Guay, Claudiane; Latour, Martin G.; Lamontagne, Julien; Lussier, Roxane; Pineda, Marco; Ruderman, Neil B.; Haemmerle, Guenter; Zechner, Rudolf; Joly, Érik; Madiraju, S. R. Murthy; Poitout, Vincent; Prentki, Marc

2009-01-01

Reduced lipolysis in hormone-sensitive lipase-deficient mice is associated with impaired glucose-stimulated insulin secretion (GSIS), suggesting that endogenous β-cell lipid stores provide signaling molecules for insulin release. Measurements of lipolysis and triglyceride (TG) lipase activity in islets from HSL−/− mice indicated the presence of other TG lipase(s) in the β-cell. Using real time-quantitative PCR, adipose triglyceride lipase (ATGL) was found to be the most abundant TG lipase in rat islets and INS832/13 cells. To assess its role in insulin secretion, ATGL expression was decreased in INS832/13 cells (ATGL-knockdown (KD)) by small hairpin RNA. ATGL-KD increased the esterification of free fatty acid (FFA) into TG. ATGL-KD cells showed decreased glucose- or Gln + Leu-induced insulin release, as well as reduced response to KCl or palmitate at high, but not low, glucose. The KATP-independent/amplification pathway of GSIS was considerably reduced in ATGL-KD cells. ATGL−/− mice were hypoinsulinemic and hypoglycemic and showed decreased plasma TG and FFAs. A hyperglycemic clamp revealed increased insulin sensitivity and decreased GSIS and arginine-induced insulin secretion in ATGL−/− mice. Accordingly, isolated islets from ATGL−/− mice showed reduced insulin secretion in response to glucose, glucose + palmitate, and KCl. Islet TG content and FFA esterification into TG were increased by 2-fold in ATGL−/− islets, but glucose usage and oxidation were unaltered. The results demonstrate the importance of ATGL and intracellular lipid signaling for fuel- and non-fuel-induced insulin secretion. PMID:19389712

Conformers, infrared spectrum and UV-induced photochemistry of matrix-isolated furfuryl alcohol.

PubMed

Araujo-Andrade, C; Gómez-Zavaglia, A; Reva, I D; Fausto, R

2012-03-08

The infrared spectra of furfuryl alcohol (2-furanmethanol, FFA) were investigated for FFA monomers isolated in low-temperature argon matrices. The structural interpretation of the obtained experimental spectra was assisted by analysis of the molecule's conformational landscape. According to the DFT(B3LYP)/6-311++G(d,p) calculations, five different minimum energy structures were found on the potential energy surface of the molecule. They can be defined by the orientation of the OCCO and CCOH dihedral angles: GG', GG, TG, TT, GT (G = +gauche, G' = -gauche, T = trans) and have a symmetry equivalent configuration: GG' = G'G, GG = G'G', TG = TG', GT = G'T. When zero-point energies are taken into account, only three (GG', GG, and TT) out of the five unique minima correspond to stable structures. The most stable conformer GG' (OCCO, 72.7°; CCOH, -59.3°), which in gas phase at room temperature accounts for ∼65% of the total population, was the only form isolated in the argon matrices at 14 K. The other two relevant forms convert into conformer GG' during matrix deposition. The low temperature glassy and crystalline states of FFA were also obtained and their infrared spectra assigned, suggesting the sole existence of the GG' conformer also in these phases. The photochemical behavior of FFA induced in situ, by tunable UV-laser, was also studied. The longest wavelength resulting in photochemical changes in the structure of the irradiated sample was found to be λ = 229 nm. Such UV irradiation of the matrix-isolated FFA led to production of formaldehyde and different isomeric C(4)H(4)O species. Cycloprop-2-ene-1-carbaldehyde and buta-2,3-dienal (two conformers) are the main initial C(4)H(4)O photoproducts formed upon short-time excitation at λ = 229 nm. But-3-ynal (two conformers) was the principal photoproduct resulting from prolonged excitation at λ= 229 nm, being consumed upon irradiation at shorter wavelengths (λ < 227.5 nm). Vinyl ketene is produced from FFA in the trans conformation and undergoes isomerization to the cis form upon irradiation at λ < 227.5 nm. Cyclopropene, propyne, allene, and CO were also identified in the irradiated matrices (in particular at the later stages of irradiation), suggesting that the photoproduced aldehydes partially decarbonylate during the performed photochemical experiments.

[Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation].

PubMed

Xu, Tao; Shi, Me; Qiu, Yun-Xia; Wang, Yan-Gang

2014-06-01

To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA-IR and negatively correlated with INS, HOMA-beta and ISI. The increase in glucagons of T2DM and IGT patients indicated inappropriate secretion of pancreatic alphabeta cells among patients with type 2 diabetes.

Seasonal variation in plasma lipids and lipases in young healthy humans.

PubMed

Cambras, Trinitat; Baena-Fustegueras, Juan A; Pardina, Eva; Ricart-Jané, David; Rossell, Joana; Díez-Noguera, Antoni; Peinado-Onsurbe, Julia

2017-01-01

Although intermediate metabolism is known to follow circadian rhythms, little information is available on the variation in lipase activities (lipoprotein and hepatic lipase, LPL and HL, respectively) and lipids throughout the year. In a cross-sectional study, we collected and analysed blood from 245 healthy students (110 men and 135 women) between 18 and 25 years old from the University of Barcelona throughout the annual campaign (March, May, October and December) of the blood bank. All subjects gave their written informed consent to participate. All blood samples were taken after breakfast at 8:00 and 11:00 am. Plasma glucose, total plasma protein, triacylglycerides (TAG), free fatty acids (FFA), free cholesterol and esterified cholesterol (FC and TC, respectively), cholesterol in low-density lipoproteins (cLDL), cholesterol in high-density lipoproteins (cHDL), phospholipids (PL) and lipase activities (LPL and HL) were determined. Cosinor analysis was used to evaluate the presence (significance of fit cosine curve to data and variance explained by rhythm) and characteristics of possible 12-month rhythms (acrophase, MESOR and amplitude). Statistically significant seasonal rhythms were detected for all the variables studied except proteins, with most of them peaking in the winter season. The lowest value for cLDL and the HL occurs in summer, while for cHDL and the LPL it is in winter. These findings demonstrate for the first time that in physiological conditions, plasma LPL and HL activities and lipids follow seasonal rhythms. The metabolic significance of this pattern is discussed.

Influence of starter culture ratios and warm room treatment on free fatty acid and amino acid in Swiss cheese.

PubMed

Ji, T; Alvarez, V B; Harper, W J

2004-07-01

Quantification of water-soluble volatile free fatty acids (FFA) and free amino acids (FAA) was performed as a ripening index and an indirect measure of flavor development in Swiss-type cheeses. The objective of this research was to assess the effect of warm room treatment (WRT) and usage ratio of starter cultures, Streptococcus thermophilus and Lactobacillus helveticus vs. propionibacteria, on the concentration of FFA and FAA in pilot plant-scale Swiss cheese. A capillary gas chromatograph equipped with a flame ionization detector was used for the analysis of FFA in Swiss cheese. Free amino acids were analyzed by the Cd-ninhydrin method. Starter culture ratios did not affect development of FAA during the cheese ripening. However, duration of WRT had an effect on the concentration of FAA in the Swiss cheese. Free amino acids increased considerably during WRT. A continuous increase in FAA was shown during 70-d ripening time after WRT. The concentrations of C2:0 and C3:0 fatty acids were affected by starter culture ratios after 2-wk WRT, but these differences had mostly disappeared after 3-wk WRT. Similar concentrations of FFA and FAA reported in previous studies were developed in Swiss cheese with a 3-wk WRT and a 0.33:1 ratio of Streptococcus thermophilus and Lactobacillus helveticus to propionibacteria.

Saturated fatty acids as possible important metabolites for epithelial ovarian cancer based on the free and esterified fatty acid profiles determined by GC-MS analysis.

PubMed

Yin, Rui; Yang, Tongshu; Su, Hui; Ying, Li; Liu, Liyan; Sun, Changhao

2016-09-26

The aims were to investigate the serum free fatty acid (FFA) and esterified fatty acid (EFA) profiles and to identify biomarkers that can be used to identify patients with epithelial ovarian cancer (EOC) based on the metabolomics approach. We applied a targeted gas chromatography-mass spectrometry metabolomics approach to serum samples from 40 EOC patients and 35 healthy controls for achieving the FFA and EFA profiles. These metabolite profiles were processed using multivariate analysis to obtain potential biomarkers. And then, some independent samples were chosen to validate these potential biomarkers. There were higher saturated fatty acids and lower unsaturated fatty acids in EOC patients when compared with the healthy controls. EFA (C16:0), EFA (C18:0) and FFA (C16:0) were identified as potential biomarkers that distinguished EOC from the healthy controls. The areas under the curve from the EFA (C16:0), EFA (C18:0) and FFA (C16:0) in validated study were 0.745, 0.701, 0.682, respectively. Our study provides useful information to bridge the gaps in our understanding to the fatty acids metabolic alterations associated with EOC, and this study has demonstrated saturated fatty acid biomarkers might be helpful for the detection and characterization of EOC patients.

Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40.

PubMed

Hidalgo, Jorge; Teuber, Stefanie; Morera, Francisco J; Ojeda, Camila; Flores, Carlos A; Hidalgo, María A; Núñez, Lucía; Villalobos, Carlos; Burgos, Rafael A

2017-04-05

Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca 2+ oscillations originated from intracellular Ca 2+ stores and were followed by store-operated Ca 2+ entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management.

Detection of Silent Type I Choroidal Neovascular Membrane in Chronic Central Serous Chorioretinopathy Using En Face Swept-Source Optical Coherence Tomography Angiography.

PubMed

Moussa, Magdy; Leila, Mahmoud; Khalid, Hagar; Lolah, Mohamed

2017-01-01

To evaluate the efficacy of SS-OCTA in the detection of silent CNV secondary to chronic CSCR compared to that of FFA and SS-OCT. A retrospective observational case series reviewing the clinical data, FFA, SS-OCT, and SS-OCTA images of patients with chronic CSCR, and comparing the findings. SS-OCTA detects the CNV complex and delineates it from the surrounding pathological features of chronic CSCR by utilizing the blood flow detection algorithm, OCTARA, and the ultrahigh-definition B-scan images of the retinal microstructure generated by swept-source technology. The bivariate correlation procedure was used for the calculation of the correlation matrix of the variables tested. The study included 60 eyes of 40 patients. Mean age was 47.6 years. Mean disease duration was 14.5 months. SS-OCTA detected type 1 CNV in 5 eyes (8.3%). In all 5 eyes, FFA and SS-OCT were inconclusive for CNV. The presence of foveal thinning, opaque material beneath irregular flat PED, and increased choroidal thickness in chronic CSCR constitutes a high-risk profile for progression to CNV development. Silent type 1 CNV is an established complication of chronic CSCR. SS-OCTA is indispensable in excluding CNV especially in high-risk patients and whenever FFA and SS-OCT are inconclusive.

Free fatty acids electronically bridge the self-assembly of a three-component nanocomplex consisting of amylose, protein, and free fatty acids.

PubMed

Zhang, Genyi; Maladen, Michelle; Campanella, Osvaldo H; Hamaker, Bruce R

2010-08-25

The self-assembly of a ternary complex, which is formed through heating and cooling of a mixture of amylose (1.0 mg/mL), whey protein isolate (50 μg/mL), and free fatty acids (FFAs, 250 μg/mL) was investigated. High-performance size-exclusion chromatography-multi-angle laser light scattering (HPSEC-MALLS) analysis showed that the complex is a water-soluble supramolecule (Mw = 6-7 × 10(6)), with a radius of gyration of 20-100 nm, indicating a nanoscale complex. Experimental results using 1-monostearyl-rac-glycerol (MSG) or cetyl alcohol that is similar to FFA in structure (except the headgroup) indicate that FFAs are the bridge between thermodynamically incompatible amylose and protein molecules and their functional carboxyl group is essential to the formation of the complex. Additionally, the effects of pH and salt treatments suggest that electrostatic interactions between negatively charged carboxyl groups of FFAs and polyionic protein are the foundation for the self-assembly of the complex. The fact that FFA is one important component in the self-assembled complex with an estimated molar ratio of 6:1:192 (amylose/protein/FFA, ∼4-5% FFA) demonstrates that it might be used as a nanocarrier for the controlled release of lipophilic functional materials to maintain their stability, bioactivity, and more importantly water solubility.

Clinical manifestations and treatment outcomes of syphilitic uveitis in HIV-negative patients in China: A retrospective case study.

PubMed

Zhu, Jiang; Jiang, Yuan; Shi, Yewen; Zheng, Bo; Xu, Zhiguo; Jia, Wei

2017-10-01

Syphilitic chorioretinitis should be included in differential diagnosis of any form of ocular inflammation. A significantly higher proportion of human immunodeficiency virus (HIV)-positive patients with ocular syphilis as compared to HIV-negative cases have been reported in published studies. However, the clinical signs and symptoms are more insidious in HIV-negative patients who are easily misdiagnosed. We report a series of cases of ocular syphilis and describe the clinical manifestations and treatment outcomes of syphilitic chorioretinitis in HIV-negative patients in China.This was a retrospective case series study. The clinical records of patients with syphilis chorioretinitis were reviewed. Demographic information and findings of fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT) were analyzed. All patients received the standard treatment. Ophthalmology examination and laboratory evaluation were repeated every 3 months. All changes were recorded. The treatment was considered successful if the patients had no inflammation in both eyes and rapid plasma reagin titer was negative after therapy.The study examined 41 eyes of 28 HIV-negative patients. The main complaints were blurry vision, floaters, and visual field defect. Twenty-seven eyes presented with panuveitis, and all had posterior involvement, including uveitis, vasculitis, chorioretinitis, and optic neuritis. The most common manifestations were uveitis and retinal vasculitis. Disc hyperfluorescence and persistent dark spots were the most common findings on FFA and ICGA. The ill-defined inner segment/outer segment junction was the most frequent manifestation on SD-OCT. Patients were diagnosed with syphilitic uveitis based on positive serological tests. Best-corrected visual acuity (BCVA) was improved in 34 eyes after treatment. Eleven patients were misdiagnosed before serological tests were performed. The delay in treatment led to long-standing cystoid macular edema and optic neuropathy, which were associated with poor BCVA (P = .037).The common manifestations of syphilitic chorioretinitis were uveitis, retinal vasculitis, and optic neuritis. Further diagnosis should be prompted by FFA, ICGA, and SD-OCT when ocular manifestation is suspected. The standard treatment for neurosyphilis was effective. If patients are presumed to be in low-risk groups such as HIV-negative, delays in diagnosis, and therapy may be likely. It is necessary to reiterate the importance of including syphilis uveitis as a differential diagnosis for any form of ocular inflammations, especially posterior uveitis and optic neuropathy.

Mitochondrial lipids in Bufo arenarum full-grown oocytes.

PubMed

Gili, Valeria; Alonso, Telma S

2004-05-01

Both the content and composition of polar and neutral lipids from the mitochondrial fraction of ovarian full-grown Bufo arenarum oocytes were analysed in the present study. Triacylglycerols (TAG) represent 33% of the total lipids, followed by phosphatidylcholine (PC), free fatty acids (FFA) and phosphatidylethanolamine (PE). Diphosphatidylglycerol (DPG) or cardiolipin, a specific component of the inner mitochondrial membrane, represents about 4% of the total lipid content. Palmitic (16:0) and arachidonic (20:4n6) acids are the most abundant fatty acids in PC and PE, respectively. DPG is enriched in fatty acids with carbon chain lengths of 18, the principal component being linoleic acid. In phosphatidylinositol (PI), 20:4n6 and stearic acid (18:0) represent about 72 mol% of the total acyl group level. The main fatty acids in TAG are linoleic (18:2), oleic (18:1), and palmitic acids. The fatty acid composition of FFA and diacylglycerols (DAG) is similar, 16:0 being the most abundant acyl group. PE is the most unsaturated lipid and sphingomyelin (SM) has the lowest unsaturation index.

Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons.

PubMed

Patil, Sachin; Chan, Christina

2005-08-26

Epidemiological studies suggest that high fat diets significantly increase the risk of Alzheimer's disease (AD). In addition, the AD brain is characterized by high fatty acid content compared to that of healthy subjects. Nevertheless, the basic mechanism relating elevated fatty acids and the pathogenesis of AD remains unclear. The present study examines the role of fatty acids in causing hyperphosphorylation of the tau protein, one of the characteristic signatures of AD pathology. Hyperphosphorylation of tau disrupts the cell cytoskeleton and leads to neuronal degeneration. Here, primary rat cortical neurons and astrocytes were treated with saturated free fatty acids (FFAs), palmitic and stearic acids. There was no change in the levels of phosphorylated tau in rat cortical neurons treated directly with these FFAs. The conditioned media from FFA-treated astrocytes, however, caused hyperphosphorylation of tau in the cortical neurons at AD-specific phospho-epitopes. Co-treatment of neurons with N-acetyl cysteine, an antioxidant, reduced FFA-induced hyperphosphorylation of tau. The present results establish a central role of FFAs in causing hyperphosphorylation of tau through astroglia-mediated oxidative stress.

Effect of pulp preconditioning on acidification, proteolysis, sugars and free fatty acids concentration during fermentation of cocoa (Theobroma cacao) beans.

PubMed

Afoakwa, Emmanuel Ohene; Quao, Jennifer; Budu, Agnes Simpson; Takrama, Jemmy; Saalia, Firibu Kwesi

2011-11-01

Changes in acidification, proteolysis, sugars and free fatty acids (FFAs) concentrations of Ghanaian cocoa beans as affected by pulp preconditioning (pod storage or PS) and fermentation were investigated. Non-volatile acidity, pH, proteolysis, sugars (total, reducing and non-reducing) and FFAs concentrations were analysed using standard methods. Increasing PS consistently decreased the non-volatile acidity with concomitant increase in pH during fermentation of the beans. Fermentation decreased the pH of the unstored beans from 6.7 to 4.9 within the first 4 days and then increased slightly again to 5.3 by the sixth day. Protein, total sugars and non-reducing sugars decreased significantly (p < 0.05) during fermentation, whereas reducing sugars and FFA increased. PS increased the FFA levels, reduced the protein content but did not have any effect on the sugars. The rate of total and non-reducing sugars degeneration with concomitant generation of reducing sugars in the cocoa beans was largely affected by fermentation than by PS.

Pentacyclic triterpenoids from Cyclocarya paliurus and their antioxidant activities in FFA-induced HepG2 steatosis cells.

PubMed

Yang, Hui-Min; Yin, Zhi-Qi; Zhao, Meng-Ge; Jiang, Cui-Hua; Zhang, Jian; Pan, Ke

2018-04-18

Six undescribed pentacyclic triterpenoids including four triterpenoid aglycones, 1β,2a,3β,23-tetrahydroxyurs-12-en-28-ursolic acid, 2a,3a,6β,19α,23-pentahydroxyurs-12-en-28-ursolic acid, 2α,3α,20β,23-tetrahydroxyurs-12-en-28-ursolic acid and 1β,2a,3β,23-tetrahydroxyurs-12,20(30)-dien-28-ursolic acid, and two triterpenoid glucosides, 2a,3a,23-trihydroxy-12,20(30)-dien-28-ursolic acid 28-O-β-d-glucopyranoside and 1-oxo-3β,23-dihydroxyolean-12-en-28-oic acid 28-O-β-d-xylopyranoside, along with 5 known triterpenoids were isolated from a CH 3 Cl-soluble extract of the leaves of Cyclocarya paliurus. Their structures were established on the basis of chemical and spectroscopic approaches. These compounds were assessed for their antioxidant effects on FFA-induced hepatic steatosis in HepG2 cells. The results revealed that three saponins and two aglycones markedly increased SOD activity and reduced MDA level. Copyright © 2018 Elsevier Ltd. All rights reserved.

Free fatty acid particles in protein formulations, part 2: contribution of polysorbate raw material.

PubMed

Siska, Christine C; Pierini, Christopher J; Lau, Hollis R; Latypov, Ramil F; Fesinmeyer, R Matthew; Litowski, Jennifer R

2015-02-01

Polysorbate 20 (PS20) is a nonionic surfactant frequently used to stabilize protein biopharmaceuticals. During the development of mAb formulations containing PS20, small clouds of particles were observed in solutions stored in vials. The degree of particle formation was dependent on PS20 concentration. The particles were characterized by reversed-phase HPLC after dissolution and labeling with the fluorescent dye 1-pyrenyldiazomethane. The analysis showed that the particles consisted of free fatty acids (FFAs), with the distribution of types consistent with those found in the PS20 raw material. Protein solutions formulated with polysorbate 80, a chemically similar nonionic surfactant, showed a substantial delay in particle formation over time compared with PS20. Multiple lots of polysorbates were evaluated for FFA levels, each exhibiting differences based on polysorbate type and lot. Polysorbates purchased in more recent years show a greater distribution and quantity of FFA and also a greater propensity to form particles. This work shows that the quality control of polysorbate raw materials could play an important role in biopharmaceutical product quality. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

The short chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M.

The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene ( Ffar2) expressionmore » is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Altogether, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.« less

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

PubMed

Takahara, Ikuko; Akazawa, Yuko; Tabuchi, Maiko; Matsuda, Katsuya; Miyaaki, Hisamitsu; Kido, Youko; Kanda, Yasuko; Taura, Naota; Ohnita, Ken; Takeshima, Fuminao; Sakai, Yusuke; Eguchi, Susumu; Nakashima, Masahiro; Nakao, Kazuhiko

2017-01-01

A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.

The short chain fatty acid receptor, FFA2, contributes to gestational glucose homeostasis

DOE PAGES

Fuller, Miles; Priyadarshini, Medha; Gibbons, Sean M.; ...

2015-09-22

The structure of the human gastrointestinal microbiota can change during pregnancy, which may influence gestational metabolism; however, a mechanism of action remains unclear. Here we observed that in wild-type (WT) mice the relative abundance of Actinobacteria and Bacteroidetes increased during pregnancy. Along with these changes, short-chain fatty acids (SCFAs), which are mainly produced through gut microbiota fermentation, significantly changed in both the cecum and peripheral blood throughout gestation in these mice. SCFAs are recognized by G protein-coupled receptors (GPCRs) such as free fatty acid receptor-2 (FFA2), and we have previously demonstrated that the fatty acid receptor-2 gene ( Ffar2) expressionmore » is higher in pancreatic islets during pregnancy. Using female Ffar2-/- mice, we explored the physiological relevance of signaling through this GPCR and found that Ffar2-deficient female mice developed fasting hyperglycemia and impaired glucose tolerance in the setting of impaired insulin secretion compared with WT mice during, but not before, pregnancy. Insulin tolerance tests were similar in Ffar2-/- and WT mice before and during pregnancy. Next, we examined the role of FFA2 in gestational β-cell mass, observing that Ffar2-/- mice had diminished gestational expansion of β-cells during pregnancy. Interestingly, mouse genotype had no significant impact on the composition of the gut microbiome, but did affect the observed SCFA profiles, suggesting a functional difference in the microbiota. Altogether, these results suggest a potential link between increased Ffar2 expression in islets and the alteration of circulating SCFA levels, possibly explaining how changes in the gut microbiome contribute to gestational glucose homeostasis.« less

Optimization and kinetic modeling of esterification of the oil obtained from waste plum stones as a pretreatment step in biodiesel production.

PubMed

Kostić, Milan D; Veličković, Ana V; Joković, Nataša M; Stamenković, Olivera S; Veljković, Vlada B

2016-02-01

This study reports on the use of oil obtained from waste plum stones as a low-cost feedstock for biodiesel production. Because of high free fatty acid (FFA) level (15.8%), the oil was processed through the two-step process including esterification of FFA and methanolysis of the esterified oil catalyzed by H2SO4 and CaO, respectively. Esterification was optimized by response surface methodology combined with a central composite design. The second-order polynomial equation predicted the lowest acid value of 0.53mgKOH/g under the following optimal reaction conditions: the methanol:oil molar ratio of 8.5:1, the catalyst amount of 2% and the reaction temperature of 45°C. The predicted acid value agreed with the experimental acid value (0.47mgKOH/g). The kinetics of FFA esterification was described by the irreversible pseudo first-order reaction rate law. The apparent kinetic constant was correlated with the initial methanol and catalyst concentrations and reaction temperature. The activation energy of the esterification reaction slightly decreased from 13.23 to 11.55kJ/mol with increasing the catalyst concentration from 0.049 to 0.172mol/dm(3). In the second step, the esterified oil reacted with methanol (methanol:oil molar ratio of 9:1) in the presence of CaO (5% to the oil mass) at 60°C. The properties of the obtained biodiesel were within the EN 14214 standard limits. Hence, waste plum stones might be valuable raw material for obtaining fatty oil for the use as alternative feedstock in biodiesel production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 6: effects of varying pancreatin and calcium levels.

PubMed

Sassene, Philip; Kleberg, Karen; Williams, Hywel D; Bakala-N'Goma, Jean-Claude; Carrière, Frédéric; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Müllertz, Anette

2014-11-01

The impact of pancreatin and calcium addition on a wide array of lipid-based formulations (LBFs) during in vitro lipolysis, with regard to digestion rates and distribution of the model drug danazol, was investigated. Pancreatin primarily affected the extent of digestion, leaving drug distribution somewhat unaffected. Calcium only affected the extent of digestion slightly but had a major influence on drug distribution, with more drug precipitating at higher calcium levels. This is likely to be caused by a combination of removal of lipolysis products from solution by the formation of calcium soaps and calcium precipitating with bile acids, events known to reduce the solubilizing capacity of LBFs dispersed in biorelevant media. Further, during the digestion of hydrophilic LBFs, like IIIA-LC, the un-ionized-ionized ratio of free fatty acids (FFA) remained unchanged at physiological calcium levels. This makes the titration curves at pH 6.5 representable for digestion. However, caution should be taken when interpreting lipolysis curves of lipophilic LBFs, like I-LC, at pH 6.5, at physiological levels of calcium (1.4 mM); un-ionized-ionized ratio of FFA might change during digestion, rendering the lipolysis curve at pH 6.5 non-representable for the total digestion. The ratio of un-ionized-ionized FFAs can be maintained during digestion by applying non-physiological levels of calcium, resulting in a modified drug distribution with increased drug precipitation. However, as the main objective of the in vitro digestion model is to evaluate drug distribution, which is believed to have an impact on bioavailability in vivo, a physiological level (1.4 mM) of calcium is preferred.

Simultaneous determination of thiamphenicol, florfenicol and florfenicol amine in eggs by reversed-phase high-performance liquid chromatography with fluorescence detection.

PubMed

Xie, Kaizhou; Jia, Longfei; Yao, Yilin; Xu, Dong; Chen, Shuqing; Xie, Xing; Pei, Yan; Bao, Wenbin; Dai, Guojun; Wang, Jinyu; Liu, Zongping

2011-08-01

A specific, sensitive and widely applicable reversed-phase high-performance liquid chromatography with fluorescence detection (RP-HPLC-FLD) method was developed for the simultaneous determination of thiamphenicol (TAP), florfenicol (FF) and florfenicol amine (FFA) in eggs. Samples were extracted with ethyl acetate-acetonitrile-ammonium hydroxide (49:49:2, v/v), defatted with hexane, followed by RP-HPLC-FLD determination. Liquid chromatography was performed on a 5 μm LiChrospher C(18) column using a mobile phase composed of acetonitrile (A), 0.01 M sodium dihydrogen phosphate containing 0.005 M sodium dodecyl sulfate and 0.1% triethylamine, adjusted to pH 4.8 by 85% phosphoric acid (B) (A:B, 35:65 v/v), at a flow rate of 1.0 mL/min. The fluorescence detector of HPLC was set at 224 nm for excitation wavelength and 290 nm for emission wavelength. Limits of detection (LODs) were 1.5 μg/kg for TAP and FF, 0.5 μg/kg for FFA in eggs; limits of quantitation (LOQs) were 5 μg/kg for TAP and FF, 2 μg/kg for FFA in eggs. Linear calibration curves were obtained over concentration ranges of 0.025-5.0 μg/mL for TAP with determination coefficients of 0.9997, 0.01-10.0 μg/mL for FF with determination coefficients of 0.9997 and 0.0025-2.50 μg/mL for FFA with determination coefficients of 0.9998, respectively. The recovery values ranged from 86.4% to 93.8% for TAP, 87.4% to 92.3% for FF and from 89.0% to 95.2% for FFA. The corresponding intra-day and inter-day variation (relative standard deviation, R.S.D.) found to be less than 6.7% and 10.8%, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance.

PubMed

Haus, Jacob M; Solomon, Thomas P J; Marchetti, Christine M; Edmison, John M; González, Frank; Kirwan, John P

2010-01-01

The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; approximately 1800 kcal; n = 11) or hypocaloric (HYPO; approximately 1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass(-1) per minute(-1)) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m(2) . min(-1)) euglycemic (5.0 mm) clamp with [3-(3)H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 +/- 0.8, 2.0 +/- 0.5, and 2.6 +/- 0.4; HYPO, 3.8 +/- 0.5, 1.2 +/- 0.3, and 2.3 +/- 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: -42 +/- 22%; HYPO: -50 +/- 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: -15 +/- 24% vs. HYPO: -58 +/- 19%, P = 0.02). Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.

Sex-specific mediation effect of the right fusiform face area volume on the association between variants in repeat length of AVPR1A RS3 and altruistic behavior in healthy adults.

PubMed

Wang, Junping; Qin, Wen; Liu, Feng; Liu, Bing; Zhou, Yuan; Jiang, Tianzi; Yu, Chunshui

2016-07-01

Microsatellite variants in the arginine vasopressin receptor 1A gene (AVPR1A) RS3 have been associated with normal social behaviors variation and autism spectrum disorders (ASDs) in a sex-specific manner. However, neural mechanisms underlying these associations remain largely unknown. We hypothesized that AVPR1A RS3 variants affect altruistic behavior by modulating the gray matter volume (GMV) of specific brain regions in a sex-specific manner. We investigated 278 young healthy adults using the Dictator Game to assess altruistic behavior. All subjects were genotyped and main effect of AVPR1A RS3 repeat polymorphisms and interaction of genotype-by-sex on the GMV were assessed in a voxel-wise manner. We observed that male subjects with relatively short repeats allocated less money to others and exhibited a significantly smaller GMV in the right fusiform face area (FFA) compared with male long homozygotes. In male subjects, the GMV of the right FFA exhibited a significant positive correlation with altruistic behavior. A mixed mediation and moderation analysis further revealed both a significant mediation effect of the GMV of the right FFA on the association between AVPR1A RS3 repeat polymorphisms and allocation sums and a significant moderation effect of sex (only in males) on the mediation effect. Post hoc analysis showed that the GMV of the right FFA was significantly smaller in male subjects carrying allele 426 than in non-426 carriers. These results suggest that the GMV of the right FFA may be a potential mediator whereby the genetic variants in AVPR1A RS3 affect altruistic behavior in healthy male subjects. Hum Brain Mapp 37:2700-2709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fires Readiness: The State of US Army Fires in Support of Combined Arms Maneuver at the Division Level

DTIC Science & Technology

2016-06-10

proficiency in their core competencies. 15. SUBJECT TERMS Fires, Fire Support, DIVARTY, FAB , Combined Arms Maneuver, DOTMLPF 16. SECURITY...FAA Functional Area Analysis FAB Field Artillery Brigade FER Final Exercise Report FFA HQ Force Field Artillery Headquarters FM Field Manual FNA...function. This provided me the opportunity to work with several Division Artillerys (DIVARTYs) and Field Artillery Brigades ( FABs ). During this time

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ni, Qian; Department of Pediatrics, Lanzhou University Second Hospital, Lanzhou; Shao, Yuan

Highlights: • Acute exposure to high altitude (HA) increased hepatic fatty acid (FA) β-oxidation. • Acute exposure of rats to HA increased hepatic FA synthesis. • PPARα and AMPK can regulate the FA metabolism. • FA may be a key energy fuel and a compensation for CHO during acute exposure to HA. • The acute changes of FA metabolism may be a mechanism of acclimatization. - Abstract: High altitude (HA) affects energy metabolism. The impact of acute and chronic HA acclimatization on the major metabolic pathways is still controversial. In this study, we aimed to unveil the impact of HAmore » on the key enzymes involved in the fatty acid (FA) metabolism in liver. Rats were exposed to an altitude of 4300 m for 30 days and the expressions of two key proteins involved in FA β-oxidation (carnitine palmitoyl transferase I, CPT-I; and peroxisome proliferator-activated receptor alpha, PPARα), two proteins involved in FA synthesis (acetyl CoA carboxylase-1, ACC-1; and AMP-activated protein kinase, AMPK), as well as the total ketone body in the liver and the plasma FFAs were examined. Rats without HA exposure were used as controls. We observed that the acute exposure of rats to HA (3 days) led to a significant increase in the expressions of CPT-I and PPARα and in the total hepatic ketone body. Longer exposure (15 days) caused a marked decrease in the expression of CPT-I and PPARα. By 30 days after HA exposure, the expression levels of CPT-I and PPARα returned to the control level. The hepatic ACC-1 level showed a significant increase in rats exposed to HA for 1 and 3 days. In contrast, the hepatic level of AMPK showed a significant reduction throughout the experimental period. Plasma FFA concentrations did not show any significant changes following HA exposure. Thus, increased hepatic FA oxidation and synthesis in the early phase of HA exposure may be among the important mechanisms for the rats to respond to the hypoxic stress in order to acclimatize themselves to the stressful environments.« less

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

PubMed

Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

Adeno-associated virus-mediated expression of myostatin propeptide improves the growth of skeletal muscle and attenuates hyperglycemia in db/db mice.

PubMed

Jiang, J G; Shen, G F; Li, J; Qiao, C; Xiao, B; Yan, H; Wang, D W; Xiao, X

2017-03-01

Inhibition of myostatin, a negative growth modulator for muscle, can functionally enhance muscle mass and improve glucose and fat metabolism in myostatin propeptide (MPRO) transgenic mice. This study was to investigate whether myostatin inhibition by adeno-associated virus (AAV)-mediated gene delivery of MPRO could improve muscle mass and achieve therapeutic effects on glucose regulation and lipid metabolism in the db/db mice and the mechanisms involved in that process. Eight-week-old male db/db mice were administered saline, AAV-GFP and AAV-MPRO/Fc vectors and monitored random blood glucose levels and body weight for 36 weeks. Body weight gain was not different during follow-up among the groups, but AAV-MPRO/Fc vectors resulted high level of MPRO in the blood companied by an increase in skeletal muscle mass and muscle hypertrophy. In addition, AAV-MPRO/Fc-treated db/db mice showed significantly lower blood glucose and insulin levels and significantly increased glucose tolerance and insulin sensitivity compared with the control groups (P<0.05). Moreover, these mice exhibited lower triglyceride (TG) and free fatty acid (FFA) content in the skeletal muscle, although no difference was observed in fat pad weights and serum TG and FFA levels. Finally, AAV-MPRO/Fc-treated mice had enhanced insulin signaling in the skeletal muscle. These data suggest that AAV-mediated MPRO therapy may provide an important clue for potential clinical applications to prevent type II diabetes, and these studies confirm that MPRO is a therapeutic target for type II diabetes.

Optimization and kinetic study of ultrasonic assisted esterification process from rubber seed oil.

PubMed

Trinh, Huong; Yusup, Suzana; Uemura, Yoshimitsu

2018-01-01

Recently, rubber seed oil (RSO) has been considered as a promising potential oil source for biodiesel production. However, RSO is a non-edible feedstock with a significant high free fatty acid (FFA) content which has an adverse impact on the process of biodiesel production. In this study, ultrasonic-assisted esterification process was conducted as a pre-treatment step to reduce the high FFA content of RSO from 40.14% to 0.75%. Response surface methodology (RSM) using central composite design (CCD) was applied to the design of experiments (DOE) and the optimization of esterification process. The result showed that methanol to oil molar ratio was the most influential factor for FFA reduction whereas the effect of amount of catalyst and the reaction were both insignificant. The kinetic study revealed that the activation energy and the frequency factor of the process are 52.577kJ/mol and 3.53×10 8 min -1 , respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrolysis optimization and characterization study of preparing fatty acids from Jatropha curcas seed oil.

PubMed

Salimon, Jumat; Abdullah, Bashar Mudhaffar; Salih, Nadia

2011-11-01

Fatty acids (FAs) are important as raw materials for the biotechnology industry. Existing methods of FAs production are based on chemical methods. In this study potassium hydroxide (KOH)-catalyzed reactions were utilized to hydrolysis Jatropha curcas seed oil. The parameters effect of ethanolic KOH concentration, reaction temperature, and reaction time to free fatty acid (FFA%) were investigated using D-Optimal Design. Characterization of the product has been studied using Fourier transforms infrared spectroscopy (FTIR), gas chromatography (GC) and high performance liquid chromatography (HPLC). The optimum conditions for maximum FFA% were achieved at 1.75M of ethanolic KOH concentration, 65°C of reaction temperature and 2.0 h of reaction time. This study showed that ethanolic KOH concentration was significant variable for J. curcas seed oil hydrolysis. In a 18-point experimental design, FFA% of hydrolyzed J. curcas seed oil can be raised from 1.89% to 102.2%, which proved by FTIR and HPLC.

External facial features modify the representation of internal facial features in the fusiform face area.

PubMed

Axelrod, Vadim; Yovel, Galit

2010-08-15

Most studies of face identity have excluded external facial features by either removing them or covering them with a hat. However, external facial features may modify the representation of internal facial features. Here we assessed whether the representation of face identity in the fusiform face area (FFA), which has been primarily studied for internal facial features, is modified by differences in external facial features. We presented faces in which external and internal facial features were manipulated independently. Our findings show that the FFA was sensitive to differences in external facial features, but this effect was significantly larger when the external and internal features were aligned than misaligned. We conclude that the FFA generates a holistic representation in which the internal and the external facial features are integrated. These results indicate that to better understand real-life face recognition both external and internal features should be included. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Fatty acid compositions of triglycerides and free fatty acids in sebum depend on amount of triglycerides, and do not differ in presence or absence of acne vulgaris.

PubMed

Akaza, Narifumi; Akamatsu, Hirohiko; Numata, Shigeki; Matsusue, Miyuki; Mashima, Yasuo; Miyawaki, Masaaki; Yamada, Shunji; Yagami, Akiko; Nakata, Satoru; Matsunaga, Kayoko

2014-12-01

To clarify the influence of the fatty acid composition of sebum in acne vulgaris, we investigated the amounts and fatty acid compositions of triglycerides (TG) and free fatty acids (FFA), and the amounts of cutaneous superficial Propionibacterium acnes in acne patients and healthy subjects. The foreheads of 18 female patients, 10 male patients, 10 healthy females and 10 healthy males were studied in a Japanese population. There were significant differences in the amounts of sebum, TG and cutaneous superficial P. acnes, as well as the fatty acid compositions of TG and FFA between acne patients and healthy subjects in females. Their fatty acid compositions were correlated with the amount of TG with or without acne. It was clarified that the fatty acid compositions of TG and FFA depended on the amount of TG, and there were no differences in the fatty acid composition in the presence and absence of acne. © 2014 Japanese Dermatological Association.

Two step esterification-transesterification process of wet greasy sewage sludge for biodiesel production.

PubMed

Urrutia, C; Sangaletti-Gerhard, N; Cea, M; Suazo, A; Aliberti, A; Navia, R

2016-01-01

Sewage sludge generated in municipal wastewater treatment plants was used as a feedstock for biodiesel production via esterification/transesterification in a two-step process. In the first esterification step, greasy and secondary sludge were tested using acid and enzymatic catalysts. The results indicate that both catalysts performed the esterification of free fatty acids (FFA) simultaneously with the transesterification of triacylglycerols (TAG). Acid catalyst demonstrated better performance in FFA esterification compared to TAG transesterification, while enzymatic catalyst showed the ability to first hydrolyze TAG in FFA, which were esterified to methyl esters. In addition, FAME concentration using greasy sludge were higher (63.9% and 58.7%), compared with those of secondary sludge (11% and 16%), using acid and enzymatic catalysts, respectively. Therefore, only greasy sludge was used in the second step of alkaline transesterification. The alkaline transesterification of the previously esterified greasy sludge reached a maximum FAME concentration of 65.4% when using acid catalyst. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of the reaction conditions on the enzyme catalyzed transesterification of castor oil: A possible step in biodiesel production.

PubMed

Andrade, Thalles A; Errico, Massimiliano; Christensen, Knud V

2017-11-01

The identification of the influence of the reaction parameters is of paramount importance when defining a process design. In this work, non-edible castor oil was reacted with methanol to produce a possible component for biodiesel blends, using liquid enzymes as the catalyst. Temperature, alcohol-to-oil molar ratio, enzyme and added water contents were the reaction parameters evaluated in the transesterification reactions. The optimal conditions, giving the optimal final FAME yield and FFA content in the methyl ester-phase was identified. At 35°C, 6.0 methanol-to-oil molar ratio, 5wt% of enzyme and 5wt% of water contents, 94% of FAME yield and 6.1% of FFA in the final composition were obtained. The investigation was completed with the analysis of the component profiles, showing that at least 8h are necessary to reach a satisfactory FAME yield together with a minor FFA content. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

PubMed

Briski, Karen P; Alenazi, Fahaad S H; Shakya, Manita; Sylvester, Paul W

2017-07-01

Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs. oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel (glucose, free fatty acids [FFA]) and energy deficit-sensitive hormone (corticosterone, glucagon, leptin) levels. FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very-long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E vs. FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, whereas FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme dopamine-β-hydroxylase (DβH) was increased in FD/O but not FD/E A2 cells. The data show discordance between A2 AMPK activation and glycemic responses to FD; sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis vs. metabolism/release in the absence vs. presence of E. Mechanisms underlying translation of E-contingent A2 neuron responses to FD into regulatory signaling remain to be determined. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Beneficial effects of cocoa, coffee, green tea, and garcinia complex supplement on diet induced obesity in rats.

PubMed

Huang, Chi-Chang; Tung, Yu-Tang; Huang, Wen-Ching; Chen, Yi-Ming; Hsu, Yi-Ju; Hsu, Mei-Chich

2016-03-12

Cocoa, coffee, green tea and garcinia contain large amounts of polyphenols. Polyphenols are well-known phytochemicals and found in plants, and have modulated physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. To evaluate the obesity-lowering effect of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) in high-energy diet (HED)-induced obese rats. Male Sprague Dawley rats (8 weeks old) were randomly divided into four groups (n = 12 per group): normal diet with vehicle treatment (Control), and HED to receive vehicle or CCGG by oral gavage at 129, 258, or 517 mg/kg/day for 4 weeks, designated the HED, 0.5X, 1X and 1X groups, respectively. HED induced macrovesicular fat in the liver and the formation of adipose tissues, and significantly increased the levels of serum free fatty acids (FFA), triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ketone bodies in serum, and hepatic TG and TC levels, and decreased the levels of high density lipoprotein cholesterol (HDL-C) in serum and lipase activity in fat tissues. Treatment with CCGG could significantly decrease the levels of FFA, TG, TC, LDL-C, and LDL-C/HDL-C, AST, ALT, and ketone bodies in serum, and hepatic TG and TC contents, and increase the levels of HDL-C in serum and lipase activity in fat tissues compared to the HED group. Liver histopathology also showed that CCGG could significantly reduce the incidence of liver lesions. These results suggested that CCGG stimulated lipid metabolism in HED-induced obese rats, which is attributable to fat mobilization from adipose tissue.

Face-selective regions differ in their ability to classify facial expressions

PubMed Central

Zhang, Hui; Japee, Shruti; Nolan, Rachel; Chu, Carlton; Liu, Ning; Ungerleider, Leslie G

2016-01-01

Recognition of facial expressions is crucial for effective social interactions. Yet, the extent to which the various face-selective regions in the human brain classify different facial expressions remains unclear. We used functional magnetic resonance imaging (fMRI) and support vector machine pattern classification analysis to determine how well face-selective brain regions are able to decode different categories of facial expression. Subjects participated in a slow event-related fMRI experiment in which they were shown 32 face pictures, portraying four different expressions: neutral, fearful, angry, and happy and belonging to eight different identities. Our results showed that only the amygdala and the posterior superior temporal sulcus (STS) were able to accurately discriminate between these expressions, albeit in different ways: The amygdala discriminated fearful faces from non-fearful faces, whereas STS discriminated neutral from emotional (fearful, angry and happy) faces. In contrast to these findings on the classification of emotional expression, only the fusiform face area (FFA) and anterior inferior temporal cortex (aIT) could discriminate among the various facial identities. Further, the amygdala and STS were better than FFA and aIT at classifying expression, while FFA and aIT were better than the amygdala and STS at classifying identity. Taken together, our findings indicate that the decoding of facial emotion and facial identity occurs in different neural substrates: the amygdala and STS for the former and FFA and aIT for the latter. PMID:26826513

Face-selective regions differ in their ability to classify facial expressions.

PubMed

Zhang, Hui; Japee, Shruti; Nolan, Rachel; Chu, Carlton; Liu, Ning; Ungerleider, Leslie G

2016-04-15

Recognition of facial expressions is crucial for effective social interactions. Yet, the extent to which the various face-selective regions in the human brain classify different facial expressions remains unclear. We used functional magnetic resonance imaging (fMRI) and support vector machine pattern classification analysis to determine how well face-selective brain regions are able to decode different categories of facial expression. Subjects participated in a slow event-related fMRI experiment in which they were shown 32 face pictures, portraying four different expressions: neutral, fearful, angry, and happy and belonging to eight different identities. Our results showed that only the amygdala and the posterior superior temporal sulcus (STS) were able to accurately discriminate between these expressions, albeit in different ways: the amygdala discriminated fearful faces from non-fearful faces, whereas STS discriminated neutral from emotional (fearful, angry and happy) faces. In contrast to these findings on the classification of emotional expression, only the fusiform face area (FFA) and anterior inferior temporal cortex (aIT) could discriminate among the various facial identities. Further, the amygdala and STS were better than FFA and aIT at classifying expression, while FFA and aIT were better than the amygdala and STS at classifying identity. Taken together, our findings indicate that the decoding of facial emotion and facial identity occurs in different neural substrates: the amygdala and STS for the former and FFA and aIT for the latter. Published by Elsevier Inc.

β-Cell lipotoxicity in response to free fatty acid elevation in prepubertal youth: African American versus Caucasian contrast.

PubMed

Michaliszyn, Sara F; Bonadonna, Riccardo C; Sjaarda, Lindsey A; Lee, Sojung; Farchoukh, Lama; Arslanian, Silva A

2013-08-01

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition × race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory.

Fixed Full Arches Supported by Tapered Implants with Knife-Edge Thread Design and Nanostructured, Calcium-Incorporated Surface: A Short-Term Prospective Clinical Study

PubMed Central

Bechara, Soheil; Lukosiunas, Algirdas; Kubilius, Ricardas

2017-01-01

Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and “complication-free” survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a “complication-free” survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes. PMID:28246595

Free fatty acid receptors and their role in regulation of energy metabolism.

PubMed

Hara, Takafumi; Kimura, Ikuo; Inoue, Daisuke; Ichimura, Atsuhiko; Hirasawa, Akira

2013-01-01

The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.

Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women.

PubMed

Ryan, Alice S; Nicklas, Barbara J; Berman, Dora M

2006-06-01

To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin-stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. We studied 33 sedentary, obese (BMI = 32 +/- 1 kg/m(2)) postmenopausal women who completed a 6-month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3-hour hyperinsulinemic-euglycemic clamp (40 mU/m(2) per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid-thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r(2) = 0.30) and M/I (r(2) = 0.33). Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population.

Deletion of Apoptosis Inhibitor of Macrophage (AIM)/CD5L Attenuates the Inflammatory Response and Infarct Size in Acute Myocardial Infarction.

PubMed

Nishikido, Toshiyuki; Oyama, Jun-ichi; Shiraki, Aya; Komoda, Hiroshi; Node, Koichi

2016-04-04

An excessive inflammatory response after myocardial infarction (MI) increases myocardial injury. The toll-like receptor (TLR)-4 is activated by the recognition of endogenous ligands and is proinflammatory when there is myocardial tissue injury. The apoptosis inhibitor of the macrophage (AIM) is known to provoke an efflux of saturated free fatty acids (FFA) due to lipolysis, which causes inflammation via the TLR-4 pathway. Therefore, this study investigated the hypothesis that AIM causes a proinflammatory response after MI. The left anterior descending coronary artery was ligated to induce MI in both AIM-knockout (AIM(-/-)) and wild-type (WT) mice. After 3 days, the inflammatory response from activation of the TLR-4/NFκB pathway was assessed, and infarct size was measured by staining with triphenyltetrazolium chloride. In addition, left ventricular remodeling was examined after 28 days. Although the area at risk was similar between AIM(-/-) and WT mice, the infarct size was significantly smaller in AIM(-/-) mice (P=0.02). The heart weight-to-body weight ratio and myocardial fibrosis were also decreased in the AIM(-/-) mice, and the 28-day survival rate was improved (P<0.01). With the reduction of plasma FFA in AIM(-/-) mice, myocardial IRAK4 and NFκB activity were decreased (all P<0.05). Moreover, there was a reduction in myeloperoxidase activity and inducible nitric oxide synthase as part of the inflammatory response (P<0.01, P=0.03, respectively). Furthermore, NFκB DNA-binding activation via TLR-4, neutrophil infiltration, and inflammatory mediators were decreased in AIM(-/-) mice. The deletion of AIM reduced the inflammatory response and infarct size and improved survival after myocardial infarction. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Characterization of constitutive and acid-induced outwardly rectifying chloride currents in immortalized mouse distal tubular cells.

PubMed

Valinsky, William C; Touyz, Rhian M; Shrier, Alvin

2017-08-01

Thiazides block Na + reabsorption while enhancing Ca 2+ reabsorption in the kidney. As previously demonstrated in immortalized mouse distal convoluted tubule (MDCT) cells, chlorothiazide application induced a robust plasma membrane hyperpolarization, which increased Ca 2+ uptake. This essential thiazide-induced hyperpolarization was prevented by the Cl - channel inhibitor 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), implicating NPPB-sensitive Cl - channels, however the nature of these Cl - channels has been rarely described in the literature. Here we show that MDCT cells express a dominant, outwardly rectifying Cl - current at extracellular pH7.4. This constitutive Cl - current was more permeable to larger anions (Eisenman sequence I; I - >Br - ≥Cl - ) and was substantially inhibited by >100mM [Ca 2+ ] o , which distinguished it from ClC-K2/barttin. Moreover, the constitutive Cl - current was blocked by NPPB, along with other Cl - channel inhibitors (4,4'-diisothiocyanatostilbene-2,2'-disulfonate, DIDS; flufenamic acid, FFA). Subjecting the MDCT cells to an acidic extracellular solution (pH<5.5) induced a substantially larger outwardly rectifying NPPB-sensitive Cl - current. This acid-induced Cl - current was also anion permeable (I - >Br - >Cl - ), but was distinguished from the constitutive Cl - current by its rectification characteristics, ion sensitivities, and response to FFA. In addition, we have identified similar outwardly rectifying and acid-sensitive currents in immortalized cells from the inner medullary collecting duct (mIMCD-3 cells). Expression of an acid-induced Cl - current would be particularly relevant in the acidic IMCD (pH<5.5). To our knowledge, the properties of these Cl - currents are unique and provide the mechanisms to account for the Cl - efflux previously speculated to be present in MDCT cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

PubMed

Wu, Yue-Yue; Zha, Ying; Liu, Jun; Wang, Fang; Xu, Jiong; Chen, Zao-Ping; Ding, He-Yuan; Sheng, Li; Han, Xiao-Jie

2016-11-17

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg -1 ·day -1 BBR (HF+LBBR group) and 380 mg·kg -1 ·day -1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Shelf life prediction of apple brownies using accelerated method

NASA Astrophysics Data System (ADS)

Pulungan, M. H.; Sukmana, A. D.; Dewi, I. A.

2018-03-01

The aim of this research was to determine shelf life of apple brownies. Shelf life was determined with Accelerated Shelf Life Testing method and Arrhenius equation. Experiment was conducted at 25, 35, and 45°C for 30 days. Every five days, the sample was analysed for free fatty acid (FFA), water activity (Aw), and organoleptic acceptance (flavour, aroma, and texture). The shelf life of the apple brownies based on FFA were 110, 54, and 28 days at temperature of 25, 35, and 45°C, respectively.

Discovery of a Potent Free Fatty Acid 1 Receptor Agonist with Low Lipophilicity, Low Polar Surface Area, and Robust in Vivo Efficacy.

PubMed

Hansen, Steffen V F; Christiansen, Elisabeth; Urban, Christian; Hudson, Brian D; Stocker, Claire J; Due-Hansen, Maria E; Wargent, Ed T; Shimpukade, Bharat; Almeida, Reinaldo; Ejsing, Christer S; Cawthorne, Michael A; Kassack, Matthias U; Milligan, Graeme; Ulven, Trond

2016-03-24

The free fatty acid receptor 1 (FFA1 or GPR40) is established as an interesting potential target for treatment of type 2 diabetes. However, to obtain optimal ligands, it may be necessary to limit both lipophilicity and polar surface area, translating to a need for small compounds. We here describe the identification of 24, a potent FFA1 agonist with low lipophilicity and very high ligand efficiency that exhibit robust glucose lowering effect.

Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity.

PubMed

Wang, Cuizhe; Ha, Xiaodan; Li, Wei; Xu, Peng; Gu, Yajuan; Wang, Tingting; Wang, Yan; Xie, Jianxin; Zhang, Jun

2017-02-01

Objective Recent studies have revealed a link between toll-like receptors (TLRs), Kruppel-like factors (KLFs), and the adipose tissue inflammation associated with obesity. TLR4 is associated with chronic inflammation in obesity. KLF7 is known to play an important role in the differentiation of adipocytes, but its role in visceral adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the correlation of TLR4 and KLF7 in inflammation induced by obesity. Methods A total of 32 Wistar male rat subjects were fed in the center for experimental animals of Shihezi University. The rats were divided into normal control (NC) and high-fat diet (HFD) group. Surgical instruments were used to collect rats' visceral adipose tissue samples in the 10th week after HFD feeding. Ninety-five Uygur subjects between 20 and 90 years old were enrolled in the present study. The subjects were divided into two groups: the normal control group (NC, 18.0 kg/m 2  ≤ BMI ≤ 23.9 kg/m 2 , n = 50) and the obesity group (OB, BMI ≥ 28 kg/m 2 , n = 45), and visceral adipose tissue was collected from the subjects. Anthropometric and clinical parameters were measured using standard procedures; biochemical indices were detected using the glucose oxidase-peroxidase method and a standardized automatic biochemistry analyzer; the plasma levels of inflammatory factors and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA and protein expression levels of key genes involved in the inflammatory signaling pathway were measured by real-time PCR and Western blot. Results In rats, compared with the NC group, the weight, Lee's index, waist circumference, visceral fat mass, and the plasma level of Glu, TG, FFA, and TNF-α were higher in the HFD group, while the plasma levels of LPT and APN were significantly lower in the HFD group in the 10th week. Furthermore, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were higher in the HFD group, and KLF7 was significantly positively correlated with LDL, TLR4, SRC, and IL-6 (P < 0.05). Meanwhile, in the Uygur population, the plasma levels of TG, LDL, and TNF-α in the OB group were significantly higher than those in the NC group (P < 0.05). Moreover, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were significantly higher in the OB group (P < 0.05), and KLF7 was significantly positively correlated with TC, TLR4, MYD88, SRC, and IL-6 (P < 0.05); the protein expression levels of TLR4 and KLF7 were significantly higher than those in the NC group (P < 0.05). Conclusion Higher expression of TLR4 and KLF7 may play a vital role in the process of inflammation induced by obesity in visceral adipose tissue.

Effects of dry period length and dietary energy source on milk yield, energy balance, and metabolic status of dairy cows over 2 consecutive years: Effects in the second year.

PubMed

Chen, J; Remmelink, G J; Gross, J J; Bruckmaier, R M; Kemp, B; van Knegsel, A T M

2016-06-01

The objective of the current study was to evaluate the effect of dry period (DP) length on milk yield, energy balance (EB), and metabolic status in cows fed a lipogenic or glucogenic diet in the second year after implementation of DP and dietary treatments. Holstein-Friesian dairy cows (n=167) were assigned randomly to 1 of 3 DP lengths (0, 30, or 60d) and 1 of 2 early lactation diets (glucogenic or lipogenic) for 2 consecutive years. Results of the first year were reported previously. In the second year, 19 cows in the 0-d DP group were attributed to a new group (0→67d DP) because these cows had a milk yield of <4kg/d at least 30d before expected calving date and were dried off. Milk yield was recorded and EB was calculated from wk -8 to 9 relative to calving. Blood samples were taken weekly from wk -3 to 8 relative to calving. Liver samples were taken in wk -2, 2, and 4 relative to calving. At the onset of lactation, cows with a 0-d or 0→67-d DP had greater body condition score (BCS) than cows with a 60-d DP. During the first 9wk, cows with a 0- or 30-d DP produced 5.0 and 4.3kg less milk per day, respectively, but had similar EB compared with cows with a 60-d DP. Cows with a 0- or 30-d DP produced additional milk precalving, which could compensate milk yield losses in the first 9wk postcalving. Cows with a 0-d DP did not have milk yield losses or improve EB in the second year as much as in the first year. Cows with a 0-d DP had greater plasma insulin and insulin-like growth factor-I (IGF-I) and lower liver triacylglycerol concentrations than cows with other DP lengths. Cows with a 0→67-d DP had lower EB, and greater plasma free fatty acids (FFA) and β-hydroxybutyrate (BHB) concentrations than cows with other DP lengths. Feeding a glucogenic diet increased plasma glucose, IGF-I, and insulin concentrations, and decreased plasma FFA, BHB, and urea concentrations compared with a lipogenic diet, independent of DP length. In conclusion, omitting the DP or feeding a glucogenic diet improved metabolic status in early lactation of the second year after implementation of DP length and dietary treatments, although effects of omitting the DP were less pronounced in the second year than in the first year. The less pronounced improvement of EB in the second year was related to the high BCS at the onset of lactation and reduced milk yield losses in cows with a 0-d DP. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparison between Canadian Canola Harvest and Export Surveys.

PubMed

Barthet, Véronique J

2016-07-20

Parameters, such as oil, protein, glucosinolates, chlorophyll content and fatty acid composition, were determined using reference methods for both harvest survey samples and Canadian Canola exports. Canola harvest survey and export data were assessed to evaluate if canola harvest survey data can be extrapolated to predict the quality of the Canadian canola exports. There were some differences in some measured parameters between harvest and export data, while other parameters showed little difference. Protein content and fatty acid composition showed very similar data for harvest and export averages. Canadian export data showed lower oil content when compared to the oil content of harvest survey was mainly due to a diluting effect of dockage in the export cargoes which remained constant over the years (1.7% to 1.9%). Chlorophyll was the least predictable parameter; dockage quality as well as commingling of the other grades in Canola No. 1 Canada affected the chlorophyll content of the exports. Free fatty acids (FFA) were also different for the export and harvest survey. FFA levels are affected by storage conditions; they increase during the shipping season and, therefore, are difficult to predict from their harvest survey averages.

[Cardiovascular and hormonal strain in waste collection workers employed in Amsa SpA, municipality of Milan, in permanent day and night work].

PubMed

Biggi, N; Consonni, D; Fragasso, G; Lattuada, G; Perseghin, G L; Verga, R; Costa, G

2007-01-01

Aim of the study is to explore in shiftworkers: a) blood pressure and hormonal variations; b) dyslipidemia and blood glucose levels; c) insulin resistence syndrome. We have assessed 48 male workers employes in Amsa SpA, a large municipal enterprise in charge of street cleaning and domestic waste collection, in permanent day and night work as hand sweepers, motor sweepers and delivery tricar drivers. 24 of those workers (daily and nightly) were normotensive and 24 were hypertensive. Our medical checks were: physical examination: BMI; laboratory findings (blood): glucose, total cholesterol, triglycerides, endothelin, insulin, FFA, HOMA S, HOMA B, HOMA R; assay of salivary cortisol and urinary cortisol in 24 h; 24 h pressure monitoring. Nightly hypertensive: increased consumption in wine and coffee, weight and BMI, total cholesterol and FFA and endothelin. Nightly normotensive: increased consumption in cigarettes and salivary cortisol. Daily hypertensive: increased total cholesterol; 24 h pressure monitoring showed more pronounced variations of pressure in night workers both normotensive and hypertensive in working time. Night shiftwork looks like more stressfull than day shiftwork. Insuline resistance isn't noticed in all four groups.

Comparison between Canadian Canola Harvest and Export Surveys

PubMed Central

Barthet, Véronique J.

2016-01-01

Parameters, such as oil, protein, glucosinolates, chlorophyll content and fatty acid composition, were determined using reference methods for both harvest survey samples and Canadian Canola exports. Canola harvest survey and export data were assessed to evaluate if canola harvest survey data can be extrapolated to predict the quality of the Canadian canola exports. There were some differences in some measured parameters between harvest and export data, while other parameters showed little difference. Protein content and fatty acid composition showed very similar data for harvest and export averages. Canadian export data showed lower oil content when compared to the oil content of harvest survey was mainly due to a diluting effect of dockage in the export cargoes which remained constant over the years (1.7% to 1.9%). Chlorophyll was the least predictable parameter; dockage quality as well as commingling of the other grades in Canola No. 1 Canada affected the chlorophyll content of the exports. Free fatty acids (FFA) were also different for the export and harvest survey. FFA levels are affected by storage conditions; they increase during the shipping season and, therefore, are difficult to predict from their harvest survey averages. PMID:27447675

Color Fundus Photography, Optical Coherence Tomography, and Fluorescein Angiography in Diagnosing Polypoidal Choroidal Vasculopathy.

PubMed

Chaikitmongkol, Voraporn; Khunsongkiet, Preeyanuch; Patikulsila, Direk; Ratanasukon, Mansing; Watanachai, Nawat; Jumroendararasame, Chaisiri; Mayerle, Catherine B; Han, Ian C; Chen, Connie J; Winaikosol, Pawara; Dejkriengkraikul, Chutikarn; Choovuthayakorn, Janejit; Kunavisarut, Paradee; Bressler, Neil M

2018-05-10

To determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis using color fundus photography (CFP), optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) without indocyanine-green angiography (ICGA). Validity analysis. Treatment-naïve eyes with serous/serosanguinous maculopathy undergoing CFP, OCT, FFA and ICGA imaging before treatment at a university-hospital in Thailand (January 2013 to June 2015) were identified. Images of each subject were categorized into 4 sets (set A: CFP; set B: CFP+OCT; set C: CFP+FFA; set D: CFP+OCT+FFA). Six graders, 3 from Thailand (PCV endemic area) and 3 from U.S. (non-endemic area), individually reviewed each set (without ICG), and determined if the presumed diagnosis was PCV. In parallel, 2 other graders confirmed if each case had PCV or not using EVEREST criteria (including ICGA). Sensitivity and specificity of a PCV diagnosis with each set (without ICGA) were analyzed compared with diagnoses including ICGA. Of 119 study eyes (113 subjects, 57% male, mean age±SD 59.9±13.8), definite PCV diagnosis was 40.3%. Sensitivity of sets A, B, C, D: 0.63 (95%CI: 0.47-0.76), 0.83 (95%CI: 0.69-0.92), 0.54 (95%CI: 0.39-0.68), 0.67 (95%CI: 0.51-0.79). Specificity were 0.93 (95% CI: 0.84-0.97), 0.83 (95%CI: 0.72-0.91), 0.97 (95%CI: 0.89-0.99), 0.92 (95%CI: 0.82-0.97). Accuracies: 0.81 (95%CI: 0.73-0.88), 0.83 (95%CI: 0.76-0.90), 0.79 (95%CI: 0.73-0.87), 0.82 (95%CI: 0.74-0.88). Discrepancies between Thai and US graders existed through sets A, C, and D. These data suggest without ICGA, fundus photography combined with OCT provides high sensitivity and high specificity to diagnosis PCV; adding FFA does not improve accuracy. Copyright © 2018 Elsevier Inc. All rights reserved.

Application of Fourier transform infrared spectroscopy for monitoring short-chain free fatty acids in Swiss cheese.

PubMed

Koca, N; Rodriguez-Saona, L E; Harper, W J; Alvarez, V B

2007-08-01

Short-chain free fatty acids (FFA) are important sources of cheese flavor and have been reported to be indicators for assessing quality. The objective of this research was to develop a simple and rapid screening tool for monitoring the short-chain FFA contents in Swiss cheese by using Fourier transform infrared spectroscopy (FTIR). Forty-four Swiss cheese samples were evaluated by using a MIRacle three-reflection diamond attenuated total reflectance (ATR) accessory. Two different sampling techniques were used for FTIR/ATR measurement: direct measurement of Swiss cheese slices (approximately 0.5 g) and measurement of a water-soluble fraction of cheese. The amounts of FFA (propionic, acetic, and butyric acids) in the water-soluble fraction of samples were analyzed by gas chromatography-flame ion-ization detection as a reference method. Calibration models for both direct measurement and the water-soluble fraction of cheese were developed based on a cross-validated (leave-one-out approach) partial least squares regression by using the regions of 3,000 to 2,800, 1,775 to 1,680, and 1,500 to 900 cm(-1) for short-chain FFA in cheese. Promising performance statistics were obtained for the calibration models of both direct measurement and the water-soluble fraction, with improved performance statistics obtained from the water-soluble extract, particularly for propionic acid. Partial least squares models generated from FTIR/ATR spectra by direct measurement of cheeses gave standard errors of cross-validation of 9.7 mg/100 g of cheese for propionic acid, 9.3 mg/100 g of cheese for acetic acid, and 5.5 mg/100 g of cheese for butyric acid, and correlation coefficients >0.9. Standard error of cross-validation values for the water-soluble fraction were 4.4 mg/100 g of cheese for propionic acid, 9.2 mg/100 g of cheese for acetic acid, and 5.2 mg/100 g of cheese for butyric acid with correlation coefficients of 0.98, 0.95, and 0.92, respectively. Infrared spectroscopy and chemometrics accurately and precisely predicted the short-chain FFA content in Swiss cheeses and in the water-soluble fraction of the cheese.

Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance

PubMed Central

Haus, Jacob M.; Solomon, Thomas P. J.; Marchetti, Christine M.; Edmison, John M.; González, Frank; Kirwan, John P.

2010-01-01

Objective: The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Research Design and Methods: Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; ∼1800 kcal; n = 11) or hypocaloric (HYPO; ∼1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass−1 per minute−1) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m2 · min−1) euglycemic (5.0 mm) clamp with [3-3H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). Results: At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 ± 0.8, 2.0 ± 0.5, and 2.6 ± 0.4; HYPO, 3.8 ± 0.5, 1.2 ± 0.3, and 2.3 ± 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: −42 ± 22%; HYPO: −50 ± 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: −15 ± 24% vs. HYPO: −58 ± 19%, P = 0.02). Conclusions: Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention. PMID:19906790

Molecular effects of leptin on peroxisome proliferator activated receptor gamma (PPAR-γ) mRNA expression in rat's adipose and liver tissue.

PubMed

Abbasi, A; Moghadam, A A; Kahrarian, Z; Abbsavaran, R; Yari, K; Alizadeh, E

2017-08-15

Leptin is a 16-kDa peptide hormone secreted by adipose tissue that participates in the regulation of energy homeostasis. The aim of this study was to determine the effect of leptin injection on mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and comparison of PPAR-γ mRNA expression in rat's adipose and liver tissue. Twenty adult male rats were divided into the following groups: Group 1asa control (n=10) that did not receive any treatment. Group 2as a treatment (n=10) that received leptin (30 µg ⁄ kg BW) intraperitoneally (ip) for two successive days. Blood samples were taken before and one day after second leptin injection for triglyceride (TG), Free Fatty Acid (FFA), HLD-cholesterol, and LDL-cholesterol measurement. Total RNA was extractedfrom the adipose tissue and liver tissues of rats.  Adipose and liver tissue cells' cDNA was synthesized to characterize the expression of PPAR-γ. Gene expression of PPAR-γ mRNA was tested by RT- PCR technique. Results show leptin decreases expression of PPAR-γ on rat. Low levels of PPAR-γ mRNA were detected in adipose and liver tissues of treatment rats in comparison to control group. In treatment group, the level of PPAR-γ mRNA in liver tissue was very lower than the adipose tissue. The levels of HDL and FFA in treatment rats were increased whereas serum levels TG, VLDL and LDL were not changed. It is concluded that leptin signal with suppressing of PPAR-γ mRNA expression in rat's adipose and liver tissues can result in lipolysis instead of lipogenesis.

Involvement of Lipid Metabolism in the Action of Phospholipase A2 Neurotoxins

DTIC Science & Technology

1992-04-15

activity by 50% toward an egg yolk substrate, but had no effect on hydrolysis of a lecithin substrate (Rosenberg et al., 1989). Lethality was not...etc.) hydrolyzed , not molecular species as evidenced in a recent review (Harris, 1985). The existence of reacylating enzymes in tissues that "restore...34 the hydrolyzed PL by attaching another FFA on to it would mean PLs will appear not to have been hydrolyzed at levels of PLA 2 activity less than the

The emerging role of promiscuous 7TM receptors as chemosensors for food intake.

PubMed

Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

2010-01-01

In recent years, several highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized of which many are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids (FFAs) and are expressed in taste tissue, the gastrointestinal (GI) tract, endocrine glands, adipose tissue, and/or kidney. This has led to the hypothesis that these receptors may act as sensors of food intake modulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue. In the present review, we describe the molecular mechanisms of nutrient-sensing of the calcium-sensing receptor (CaR), the G protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1 receptor T1R1/T1R3-sensing L-α-amino acids; the carbohydrate-sensing T1R2/T1R3 receptor; the proteolytic degradation product sensor GPR93 (also termed GPR92); and the FFA sensing receptors FFA1, FFA2, FFA3, GPR84, and GPR120. Due to their omnipresent nature, the natural ligands have had limited usability in pharmacological/physiological studies which has hampered the elucidation of the physiological function and therapeutic prospect of their receptors. However, an increasing number of subtype-selective ligands and/or receptor knockout mice are being developed which at least for some of the receptors have validated them as promising drug targets in, for example, type II diabetes. Copyright © 2010 Elsevier Inc. All rights reserved.

Concomitant Action of Structural Elements and Receptor Phosphorylation Determines Arrestin-3 Interaction with the Free Fatty Acid Receptor FFA4*

PubMed Central

Butcher, Adrian J.; Hudson, Brian D.; Shimpukade, Bharat; Alvarez-Curto, Elisa; Prihandoko, Rudi; Ulven, Trond; Milligan, Graeme; Tobin, Andrew B.

2014-01-01

In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr347, Thr349, Ser350, Ser357, and Ser360) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu341, Asp348, and Asp355 located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling. PMID:24817122

Synthesis of silica gel from waste glass bottles and its application for the reduction of free fatty acid (FFA) on waste cooking oil

NASA Astrophysics Data System (ADS)

Sudjarwo, Wisnu Arfian A.; Bee, Mei Magdayanti F.

2017-06-01

Synthesis of silica gel from waste glass bottles was conducted with aims to characterize the product and to analyze its application forthe reduction of free fatty acid (FFA) on waste cooking oil. Silica source taken from waste glass bottles was synthesized into silica gel by using the sol-gel method. Several types of silica gel were produced with three different weight ratios of waste glass and sodium hydroxide as an extractor. They were: 1:1, 1:2, and 1:3. The results indicated that synthesized silica possessed morphology innano-sizedranging from 85 nm to 459 nm. Adsorption performance was investigated by a batch system atthe temperature between 70°C and 110°C by a range of 10°C in an hour. Analysis of the adsorption characteristic showed that the highest efficiency value of FFA reduction of 91% was obtained by silica gel with ratiosof 1:1 (SG 1) and 1:3 (SG 3). Their performances were also followed by the decline of the refractive index and the density of waste cooking oil.

Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

PubMed

Desbois, Andrew P; Smith, Valerie J

2010-02-01

Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

Aging per se Increases the Susceptibility to Free Fatty Acid–Induced Insulin Resistance

PubMed Central

Huffman, Derek M.; Fishman, Sigal; Jerschow, Elina; Heo, Hye J.; Atzmon, Gil; Schechter, Clyde; Muzumdar, Radhika H.

2010-01-01

Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic–euglycemic clamp in three groups of rats: young ad libitum–fed (YAL), old ad libitum–fed (OAL), and old on lifelong calorie restriction (OCR). The OCR group was included to distinguish between aging per se and age-related changes in body fat distribution. IL induced marked insulin resistance in both YAL and OCR, but the onset of insulin resistance was approximately two to three times more rapid in OCR as compared with YAL. In response to IL infusion, plasminogen-activating inhibitor-1 (PAI-1) expression was increased in subcutaneous fat from OAL animals. In visceral fat, a marked increase in PAI-1 and interleukin-6 expression was observed in OAL and OCR rats, but not YAL, in response to IL treatment. Thus, aging per se increases the inflammatory response to excess nutrients and vulnerability to FFA-induced insulin resistance with aging. PMID:20504893

Effect of unsaturated fatty acids and triglycerides from soybeans on milk fat synthesis and biohydrogenation intermediates in dairy cattle.

PubMed

Boerman, J P; Lock, A L

2014-11-01

Increased rumen unsaturated fatty acid (FA) load is a risk factor for milk fat depression. This study evaluated if increasing the amount of unsaturated FA in the diet as triglycerides or free FA affected feed intake, yield of milk and milk components, and feed efficiency. Eighteen Holstein cows (132 ± 75 d in milk) were used in a replicated 3 × 3 Latin square design. Treatments were a control (CON) diet, or 1 of 2 unsaturated FA (UFA) treatments supplemented with either soybean oil (FA present as triglycerides; TAG treatment) or soybean FA distillate (FA present as free FA; FFA treatment). The soybean oil contained a higher concentration of cis-9 C18:1 (26.0 vs. 11.8 g/100g of FA) and lower concentrations of C16:0 (9.6 vs. 15.0 g/100g of FA) and cis-9,cis-12 C18:2 (50.5 vs. 59.1g/100g of FA) than the soybean FA distillate. The soybean oil and soybean FA distillate were included in the diet at 2% dry matter (DM) to replace soyhulls in the CON diet. Treatment periods were 21 d, with the final 4 d used for sample and data collection. The corn silage- and alfalfa silage-based diets contained 23% forage neutral detergent fiber and 17% crude protein. Total dietary FA were 2.6, 4.2, and 4.3% of diet DM for CON, FFA, and TAG treatments, respectively. Total FA intake was increased 57% for UFA treatments and was similar between FFA and TAG. The intakes of individual FA were similar, with the exception of a 24 g/d lower intake of C16:0 and a 64 g/d greater intake of cis-9 C18:1 for the TAG compared with the FFA treatment. Compared with CON, the UFA treatments decreased DM intake (1.0 kg/d) but increased milk yield (2.2 kg/d) and milk lactose concentration and yield. The UFA treatments reduced milk fat concentration, averaging 3.30, 3.18, and 3.11% for CON, FFA, and TAG treatments, respectively. Yield of milk fat, milk protein, and 3.5% fat-corrected milk remained unchanged when comparing CON with the UFA treatments. No differences existed in the yield of milk or milk components between the FFA and TAG treatments. The UFA treatments increased feed efficiency (energy-corrected milk/DM intake), averaging 1.42, 1.53, and 1.48 for CON, FFA, and TAG treatments, respectively. Although milk fat yield was not affected, the UFA treatments decreased the yield of de novo (<16-carbon) synthesized FA (40 g/d) and increased the yield of preformed (>16-carbon) FA (134 g/d). Yield of FA from both sources (16-carbon FA) was reduced by the UFA treatments but to a different extent for FFA versus TAG (72 vs. 100g/d). An increase was detected in the concentration of trans-10 C18:1 and a trend for an increase in trans-10,cis-12 C18:2 and trans-9,cis-11 C18:2 for the UFA treatments compared with CON. Under the dietary conditions tested, UFA treatments supplemented at 2% diet DM as either soybean FA distillate or soybean oil increased milk yield but did not effectively cause a reduction in milk fat yield, with preformed FA replacing de novo synthesized FA in milk fat. Further research is required to determine if the response to changes in dietary free and esterified FA concentrations is different in diets that differ in their risk for milk fat depression. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reduced Cortisol and Metabolic Responses of Thin Ewes to an Acute Cold Challenge in Mid-Pregnancy: Implications for Animal Physiology and Welfare

PubMed Central

Verbeek, Else; Oliver, Mark Hope; Waas, Joseph Rupert; McLeay, Lance Maxwell; Blache, Dominique; Matthews, Lindsay Ross

2012-01-01

Background Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal's ability to cope with cold challenges. Methods Eighteen pregnant ewes with a BCS of 2.7±0.1 were fed to attain low (LBC: BCS2.3±0.1), medium (MBC: BCS3.2±0.2) or high BCS (HBC: BCS3.6±0.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.4±0.1°C) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. Results During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P<0.01, P<0.01 and P<0.05, respectively) and HBC ewes (P<0.05, P<0.01 and P<0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P<0.05) and HBC ewes (P<0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P<0.05 and P<0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P<0.01). Glucose concentrations and internal body temperature (Tcore) increased in all treatments, although peak Tcore tended to be higher in HBC ewes (P<0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P<0.05). Conclusion Even though all ewes were able to increase Tcore and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced. PMID:22662144

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents

PubMed Central

Rauch, Lindsey; Huang, Hong; Bauer, John A.; Hoffman, Robert P.

2016-01-01

Abstract Background: Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Methods: Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast® and 12 ounce Sprite®) in obese adolescents (10–13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Results: Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. Conclusions: These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear. PMID:27419255

PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis.

PubMed

Perttilä, Julia; Huaman-Samanez, Carolina; Caron, Sandrine; Tanhuanpää, Kimmo; Staels, Bart; Yki-Järvinen, Hannele; Olkkonen, Vesa M

2012-05-15

Liver fat is increased in carriers of the minor G allele in rs738409 (I148M amino acid substitution) in patatin-like phospholipase domain-containing 3 (PNPLA3)/adiponutrin. We studied transcriptional regulation of PNPLA3 in immortalized human hepatocytes (IHH) and human hepatoma cells (HuH7) and the impact of PNPLA3 I148M mutant on hepatocyte triglyceride metabolism. Studies in IHH showed that silencing of the carbohydrate response element-binding protein (ChREBP) abolished induction of PNPLA3 mRNA by glucose. Glucose-dependent binding of ChREBP to a newly identified carbohydrate response element in the PNPLA3 promoter was demonstrated by chromatin immunoprecipitation. Adenoviral overexpression of mouse ChREBP in IHH failed to induce PNPLA3 mRNA. [(3)H]acetate or [(3)H]oleate incorporation with 1-h pulse labeling or 18-h [(3)H]oleate labeling in HuH7 cells showed no effect of PNPLA3 I148M on triglyceride (TG) synthesis in the absence of free fatty acid (FFA) loading. Increased [(3)H]oleate accumulation into triglycerides in I148M-expressing cells was observed after 18 h of labeling in the presence of 200 μM FFA-albumin complexes. This was accompanied by increased PNPLA3 protein levels. The rate of hydrolysis of [(3)H]TG during lipid depletion was decreased significantly by PNPLA3 I148M. Our results suggest that PNPLA3 is regulated in human hepatocytes by glucose via ChREBP. PNPLA3 I148M enhances cellular accumulation of [(3)H]TG in the presence of excess FFA, which is known to stabilize PNPLA3 protein. These data do not exclude an effect of PNPLA3 I148M on hepatocyte lipogenesis but show that the mutant increases the stability of triglycerides.

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents.

PubMed

Cazeau, Rachel-Marie; Rauch, Lindsey; Huang, Hong; Bauer, John A; Hoffman, Robert P

2016-09-01

Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast(®) and 12 ounce Sprite(®)) in obese adolescents (10-13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear.

Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

PubMed Central

Pan, Youdong; Tian, Tian; Park, Chang Ook; Lofftus, Serena Y.; Mei, Shenglin; Liu, Xing; Luo, Chi; O’Malley, John T.; Gehad, Ahmed; Teague, Jessica E.; Divito, Sherrie J.; Fuhlbrigge, Robert; Puigserver, Pere; Krueger, James G.; Hotamisligil, Gökhan S.; Clark, Rachael A.; Kupper, Thomas S.

2017-01-01

Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens1–4. However, the biological pathways that enable the long-term survival of TRM cells are obscure4,5. Here we show that mouse CD8+ TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8+ TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes. In vitro, CD8+ TRM cells, but not CD8+ TCM, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8+ TRM cells. The persistence of CD8+ TRM cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8+ TRM cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8+ TRM cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity. PMID:28219080

[Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

PubMed

Lin, Juan-Na; Kuang, Qiao-Ting; Ye, Kai-He; Ye, Chun-Ling; Huang, Yi; Zhang, Xiao-Qi; Ye, Wen-Cai

2013-08-01

To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P < 0.05 or P < 0.01). Compared with the model group, ursolic acid at 100 micromol/L could enhance cellular glucose uptake of insulin resistant adipocyte significantly both in basic and insulin stimulation state (P < 0.01), while ursolic acid at 30 micromol/L could already enhance its glucose uptake significantly (P < 0.05), and could already decrease its FFA production significantly (P < 0.05). Ursolic acid at 30 micromol/L could increase the secretion of adiponectin on insulin resistant adipocyte significantly (P < 0.05), up-regulate the expression of PPARgamma protein (P < 0.05), but showed no effect on the PTP1B protein expression (P > 0.05). Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions.

PubMed

Lam, Ching-Wan; Law, Chun-Yiu

2014-09-05

Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical method used for broad-spectrum identification and quantification of metabolites in biofluids in human health and disease states. In this study, we exploit metabolomic profiling for cancer biomarker discovery for diagnosis of malignant pleural effusions. We envisage the result will be clinically useful since currently there are no cancer biomarkers that are accurate enough for the diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural effusions from lung cancer patients and 18 benign effusions from patients with pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). Insignificant markers were filtered out using a metabolome-wide significance level (MWSL) with p-value < 2 × 10(-5) for t test. Only compounds in Human Metabolome Database (HMDB) will be used as cancer biomarkers. ROCCET analysis of ESI positive and negative MS spectra revealed free fatty acid (FFA) 18:1 (oleic acid) had the largest area-under-ROC of 0.96 (95% CI = 0.87-1.00) in malignant pleural effusions. Using a ratio of FFA 18:1-to-ceramide (d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91-1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be determined objectively. This lipogenic phenotype could be explained by overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for diagnosis of malignant pleural effusions.

Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes.

PubMed

Tsuzuki, Takamasa; Kobayashi, Hiroyuki; Yoshihara, Toshinori; Kakigi, Ryo; Ichinoseki-Sekine, Noriko; Naito, Hisashi

2017-03-01

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.

Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients.

PubMed

Wellendorph, Petrine; Johansen, Lars Dan; Bräuner-Osborne, Hans

2009-09-01

A number of highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized within the last few years. It is noteworthy that many of these receptors are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids and are expressed in taste tissue, the gastrointestinal tract, endocrine glands, adipose tissue, and/or kidney. These receptors thus hold the potential to act as sensors of food intake, regulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue. The promiscuous tendency in ligand recognition of these receptors is in contrast to the typical specific interaction with one physiological agonist seen for most receptors, which challenges the classic "lock-and-key" concept. We here review the molecular mechanisms of nutrient sensing of the calcium-sensing receptor, the G protein-coupled receptor family C, group 6, subtype A (GPRC6A), and the taste1 receptor T1R1/T1R3, which are sensing L-alpha-amino acids, the carbohydrate-sensing T1R2/T1R3 receptor, the proteolytic degradation product sensor GPR93 (also termed GPR92), and the free fatty acid (FFA) sensing receptors FFA1, FFA2, FFA3, GPR84, and GPR120. The involvement of the individual receptors in sensing of food intake has been validated to different degrees because of limited availability of specific pharmacological tools and/or receptor knockout mice. However, as a group, the receptors represent potential drug targets, to treat, for example, type II diabetes by mimicking food intake by potent agonists or positive allosteric modulators. The ligand-receptor interactions of the promiscuous receptors of organic nutrients thus remain an interesting subject of emerging functional importance.

Targeting of free fatty acid receptor 1 in EOC: A novel strategy to restrict the adipocyte-EOC dependence.

PubMed

Munkarah, Adnan; Mert, Ismail; Chhina, Jasdeep; Hamid, Suhail; Poisson, Laila; Hensley-Alford, Sharon; Giri, Shailendra; Rattan, Ramandeep

2016-04-01

Adipocyte derived free fatty acids (FFA) promote epithelial ovarian cancer (EOC) by acting as a fuel source to support the energy requirement of the cancer cells. FFA may also exert biological effects through signaling pathways. Recently, a family of FFA activated G-protein coupled receptors (FFAR/GPCRs) was identified. Our objective was to investigate the role of FFAR/GPCRs in EOC and assess their potential as therapeutic targets. The mRNA (RT-PCR) expression of FFAR/GPCR family members (FFAR1/GPR40; FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120 and GPR84) was examined in: (1) a syngeneic mouse model of EOC fed high energy diet (60% fat) or regular diet (30% fat), (2) EOC cell lines exposed to free fatty acids and (3) specimens from 13 histologically normal ovaries and 28 high grade ovarian serous carcinomas. The GPR 40 antagonist, GW1100, was used to inhibit FFAR1/GPR40 and cell survival was assayed by MTT in various cell lines. High Grade Serous carcinoma specimens expressed significantly increased GPR40 compared to normal ovaries (p=0.0020). Higher expression was noted in advanced stage disease. ID8 ovarian tumors from mice fed with high fat diet also showed higher GPR40 expression. Exposing EOC cells to FFAs, increased GPR40 expression. Treatment of EOC cell lines with GW100 resulted in growth inhibition and was associated with an alteration in their energy metabolism. FFA-induced cancer cell growth may be partly mediated through FFAR1/GPR40. Targeting of FFAR1/GPR40 may be an attractive treatment strategy in EOC, and possibly offers a targeted treatment for a subset of EOC patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1).

PubMed

Kiryakova, S; Söhnchen, J; Grosheva, M; Schuetz, U; Marinova, Ts; Dzhupanova, R; Sinis, N; Hübbers, C U; Skouras, E; Ankerne, J; Fries, J W U; Irintchev, A; Dunlop, S A; Angelov, D N

2010-04-01

Recently, we showed that manual stimulation (MS) of denervated vibrissal muscles enhanced functional recovery following facial nerve cut and suture (FFA) by reducing poly-innervation at the neuro-muscular junctions (NMJ). Although the cellular correlates of poly-innervation are established, with terminal Schwann cells (TSC) processes attracting axon sprouts to "bridge" adjacent NMJ, molecular correlates are poorly understood. Since quantitative RT-PCR revealed a rapid increase of IGF-1 mRNA in denervated muscles, we examined the effect of daily MS for 2 months after FFA in IGF-1(+/-) heterozygous mice; controls were wild-type (WT) littermates including intact animals. We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive TSC. There were no differences between intact WT and IGF-1(+/-) mice for vibrissal whisking amplitude (48 degrees and 49 degrees ) or the percentage of bridged NMJ (0%). After FFA and handling alone (i.e. no MS) in WT animals, vibrissal whisking amplitude was reduced (60% lower than intact) and the percentage of bridged NMJ increased (42% more than intact). MS improved both the amplitude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (12% more than intact). After FFA and handling in IGF-1(+/-) mice, the pattern was similar (whisking amplitude 57% lower than intact; proportion of bridged NMJ 42% more than intact). However, MS did not improve outcome (whisking amplitude 47% lower than intact; proportion of bridged NMJ 40% more than intact). We conclude that IGF-I is required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function. Copyright 2010 Elsevier Inc. All rights reserved.

Concomitant action of structural elements and receptor phosphorylation determines arrestin-3 interaction with the free fatty acid receptor FFA4.

PubMed

Butcher, Adrian J; Hudson, Brian D; Shimpukade, Bharat; Alvarez-Curto, Elisa; Prihandoko, Rudi; Ulven, Trond; Milligan, Graeme; Tobin, Andrew B

2014-06-27

In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr(347), Thr(349), Ser(350), Ser(357), and Ser(360)) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu(341), Asp(348), and Asp(355) located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

PubMed

Obanda, Diana N; Zhao, Peng; Richard, Allison J; Ribnicky, David; Cefalu, William T; Stephens, Jacqueline M

2016-01-01

Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner

PubMed Central

Obanda, Diana N.; Zhao, Peng; Richard, Allison J.; Ribnicky, David; Cefalu, William T.; Stephens, Jacqueline M.

2016-01-01

Objective Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. Research Design We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. Results As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. Conclusions In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial. PMID:26939068

Bacterial production of free fatty acids from freshwater macroalgal cellulose

PubMed Central

Hoovers, Spencer W.; Marner, Wesley D.; Brownson, Amy K.; Lennen, Rebecca M.; Wittkopp, Tyler M.; Yoshitani, Jun; Zulkifly, Shahrizim; Graham, Linda E.; Chaston, Sheena D.; McMahon, Katherine D.

2013-01-01

The predominant strategy for using algae to produce biofuels relies on the overproduction of lipids in microalgae with subsequent conversion to biodiesel (methyl-esters) or green diesel (alkanes). Conditions that both optimize algal growth and lipid accumulation rarely overlap, and differences in growth rates can lead to wild species outcompeting the desired lipid-rich strains. Here, we demonstrate an alternative strategy in which cellulose contained in the cell walls of multicellular algae is used as a feedstock for cultivating biofuel-producing micro-organisms. Cellulose was extracted from an environmental sample of Cladophora glomerata-dominated periphyton that was collected from Lake Mendota, WI, USA. The resulting cellulose cake was hydrolyzed by commercial enzymes to release fermentable glucose. The hydrolysis mixture was used to formulate an undefined medium that was able to support the growth, without supplementation, of a free fatty acid (FFA)-overproducing strain of Escherichia coli (Lennen et. al 2010). To maximize free fatty acid production from glucose, an isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible vector was constructed to express the Umbellularia californica acyl–acyl carrier protein (ACP) thioesterase. Thioesterase expression was optimized by inducing cultures with 50 μM IPTG. Cell density and FFA titers from cultures grown on algae-based media reached 50% of those (~90 μg/mL FFA) cultures grown on rich Luria–Bertani broth supplemented with 0.2% glucose. In comparison, cultures grown in two media based on AFEX-pretreated corn stover generated tenfold less FFA than cultures grown in algae-based media. This study demonstrates that macroalgal cellulose is a potential carbon source for the production of biofuels or other microbially synthesized compounds. PMID:21643704

Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue

PubMed Central

Ali, Asem H.; Koutsari, Christina; Mundi, Manpreet; Stegall, Mark D.; Heimbach, Julie K.; Taler, Sandra J.; Nygren, Jonas; Thorell, Anders; Bogachus, Lindsey D.; Turcotte, Lorraine P.; Bernlohr, David; Jensen, Michael D.

2011-01-01

OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol ⋅ kg adipose lipid−1 ⋅ min−1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation. PMID:21810594

Reperfusion of occluded branch retinal arteries by transluminal Nd:YAG laser embolysis combined with intravenous thrombolysis of urokinase

PubMed Central

Chai, Fang; Du, Shanshuang; Zhao, Xiquan

2017-01-01

Purpose: To report successful treatment with transluminal Nd:YAG laser embolysis (TYE) combined with urokinase thrombolysis for reperfusion of occluded branch retinal arteries with visible emboli. Methods: A total of 34 eyes from 34 patients with acute, severe vision loss secondary to a branch retinal artery occlusion with visible emboli and retinal whitening were examined. Each patient was administered TYE therapy, which focused on the embolus, using an ocular contact lens; a 0.3–0.9 mJ laser pulse was delivered directly and gradually according to the reaction. Fundus photographs and fundus fluorescein angiography (FFA) were obtained before and immediately after the laser treatment. All patients received urokinase thrombolysis therapy drops intravenously for 5 days at 10–20 u/d. The follow-up period ranged from 6 to 14 months after therapy. The morphological characteristics of FFA associated with obstruction recovery of arterial fluorescence filling and visual function were analyzed. Results: After TYE therapy, FFA examinations showed that the retinal artery and its branches exhibited completely restored blood flow without obstruction in 13 eyes, accounting for 38.2% of the cases. The blood flow was mostly recovered in 11 eyes (32.4% of patients). FFA examinations following the combined intravenous urokinase thrombolysis therapy showed that the retinal artery and its branches exhibited completely restored blood flow after obstruction in 16 eyes (47.1% of patients). The blood flow was mostly recovered in 15 eyes (44.1% of patients). Conclusion: TYE combined with urokinase thrombolysis is effective for reperfusion of occluded branch retinal arteries and improving visual recovery in patients with visible emboli. PMID:29162667