Note: This page contains sample records for the topic elevated triglycerides tg from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPAR? signaling  

PubMed Central

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor ? (PPAR?). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [3H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [3H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPAR? target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPAR?-dependent processes also in the small intestine.

Obrowsky, Sascha; Chandak, Prakash G.; Patankar, Jay V.; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E.; Bogner-Strauss, Juliane G.; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

2013-01-01

2

Triglycerides  

MedlinePLUS

Triglycerides are a type of fat found in your blood. Too much of this type of fat ... especially in women. A blood test measures your triglycerides along with your cholesterol. Normal triglyceride levels are ...

3

Rapid reduction of severely elevated serum triglycerides with insulin infusion, gemfibrozil and niacin.  

PubMed

The conventional methods of treatment of severe hypertriglyceridemia are dietary restriction and lipid lowering medications, mainly fibric acid derivatives. In the medical literature, use of insulin infusion to treat hypertriglyceridemia has not been highlighted sufficiently. We report a 53-year-old male who presented with a four-day history of epigastric pain. The patient's clinical history was significant for hypertriglyceridemia, type-2 diabetes mellitus with medication noncompliance, obesity, status post-gastric bypass surgery, and alcohol abuse with prior admissions for detoxification. Physical examination revealed mild epigastric tenderness. Laboratory studies revealed severely elevated serum triglyceride (TG) level (8116 mg/dL). Computed tomography (CT) scan of the abdomen exhibited no evidence of pancreatitis. Regular insulin infusion was started at 3 U/h and gradually increased to 7-10 U/h. Dextrose infusion was titrated to avoid hypoglycemia and maintain blood glucose levels below 150 mg/dL. Gemfibrozil and niacin were also started. After 24 hours, his TG levels were decreased to 2501 mg/dL. Insulin infusion was continued for about 48 hours. A low carbohydrate diet excluding simple carbohydrates was given. The patient's serum TG levels normalized over a period of one month. Thus insulin infusion can be considered a safe modality of treatment for rapid reduction of serum TG in addition to fibrates and niacin. PMID:20852089

Poonuru, Sujani; Pathak, Sumedha R; Vats, Hemender S; Pathak, Ram D

2011-03-01

4

Genetic variation in Tanis was associated with elevating plasma triglyceride level in Chinese nondiabetic subjects  

PubMed Central

Background The association of genetic polymorphisms of Tanis with triglyceride concentration in human has not been thoroughly examined. We aimed to investigate the relationship between triglyceride concentrations and Tanis genetic polymorphisms. Methods All participants (n=1497) selected from subjects participating in the Cardiovascular Risk Survey (CRS) study were divided into two groups according to ethnicity (Han: n=1059; Uygur: n= 438). Four tagging SNPs (rs12910524, rs1384565, rs2101171, rs4965814) of Tanis gene were genotyped using TaqMan® assays from Applied Biosystems following the manufacturer’s suggestions and analyzed in an ABI 7900HT Fast Real-Time PCR System. Results We found that the SNP rs12910524 was associated with triglyceride levels by analyses of a dominant model (P<0.001), recessive model (P <0.001) and additive model (P < 0.001) not only in Han ethnic but also in Uygur ethnic group, and the difference remained significant after the adjustment of sex, age, alcohol intake, smoking, BMI and plasma glucose (GLU) level (All P < 0.001). However, this relationship was not observed in rs1384565, rs2101171, and rs4965814 before and after multivariate adjustment (All P > 0.05). Furthermore, there were significant interactions between rs12910524 and GLU on TG both in Han (P=0.001) and Uygur population (P=2.60×10-4). Conclusion Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China.

2013-01-01

5

CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid  

SciTech Connect

Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria ?-oxidation. -- Highlights: ? Isoniazid metabolites were elevated only in wild-type mice. ? Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ? Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ? Bile acid transporters were significantly decreased in isoniazid-treated mice.

Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)] [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)] [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2013-01-15

6

Modulation of plasma TG lipolysis by Angiopoietin-like proteins and GPIHBP1  

Microsoft Academic Search

There is evidence that elevated plasma triglycerides (TG) serve as an independent risk factor for coronary heart disease. Plasma TG levels are determined by the balance between the rate of production of chylomicrons and VLDL in intestine and liver, respectively, and their rate of clearance in peripheral tissues. Lipolytic processing of TG-rich lipoproteins is mediated by the enzyme lipoprotein lipase

Laeticia Lichtenstein; Sander Kersten

2010-01-01

7

Insulin resistance and elevated triglyceride in muscle: more important for survival than 'thrifty' genes?  

PubMed Central

Elevated intramyocellular triglyceride (IMTG) is strongly associated with insulin resistance, though a cause and effect relationship has not been fully described. Insulin sensitivity and IMTG content are both dynamic and can alter rapidly in response to dietary variation, physical activity and thermoregulatory response. Physically active humans (athletes) display elevated IMTG content, but in contrast to obese persons, are insulin sensitive. This paradox has created confusion surrounding the role of IMTG in the development of insulin resistance. In this review we consider the modern athlete as the physiological archetype of the Late Palaeolithic hunter–gatherer to whom the selection pressures of food availability, predation and fluctuating environmental conditions applied and to whom the genotype of modern man is virtually identical. As food procurement by the hunter–gatherer required physical activity, ‘thrifty’ genes that encouraged immediate energy storage upon refeeding after food deprivation (Neel, 1962) must have been of secondary importance in survival to genes that preserved physical capacity during food deprivation. Similarly genes that enabled survival during cold exposure whilst starved would be of primary importance. In this context, we discuss the advantage afforded by an elevated IMTG content, and how under these conditions, a concomitant muscle resistance to insulin-mediated glucose uptake would also be advantageous. In sedentary modern man, adiposity is high and skeletal muscle appears to respond as if a state of starvation exists. In this situation, elevated plasma lipids serve to accrue lipid and induce insulin resistance in skeletal muscle. Reversal of this physiological state is primarily dependant on adequate contractile activity, however, in modern Western society, physical inactivity combined with abundant food and warmth has rendered IMTG a redundant muscle substrate.

Stannard, S R; Johnson, N A

2004-01-01

8

3xTgAD mice exhibit altered behavior and elevated A? after chronic mild social stress  

PubMed Central

Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal A?, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of A? oligomers and intraneuronal A?, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates A? accumulation and impairs neurotrophic signaling.

Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P

2014-01-01

9

Circulating Triglycerides Impact on Orexigenic Peptides and Neuronal Activity in Hypothalamus  

Microsoft Academic Search

Little is known about the impact of circulating lipids on brain processes. Building on evidence that chronic fat consumption stimulates hypothalamic peptides in close association with elevated triglycerides (TG), this study examined whether an acute rise in TG levels induced by fat emulsion can affect these hypothalamic systems. In normal weight rats, ip injection of Intralipid (20%, 5 ml) during

GUO-QING CHANG; OLGA KARATAYEV; ZOYA DAVYDOVA; SARAH F. LEIBOWITZ

2004-01-01

10

Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S  

PubMed Central

Caspase-1 is known to activate the proinflammatory cytokines IL-1? and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion.

van Diepen, Janna A.; Stienstra, Rinke; Vroegrijk, Irene O. C. M.; van den Berg, Sjoerd A. A.; Salvatori, Daniela; Hooiveld, Guido J.; Kersten, Sander; Tack, Cees J.; Netea, Mihai G.; Smit, Johannes W.A.; Joosten, Leo A. B.; Havekes, Louis M.; van Dijk, Ko Willems; Rensen, Patrick C. N.

2013-01-01

11

Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate?  

PubMed Central

Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ?150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented. Conclusions In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL2-C and HDL3-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL3-C by promoting TG-rich lipoprotein catabolism and may increase HDL2-C by promoting the conversion of HDL3 to HDL2.

Sakuma, Nagahiko; Ikeuchi, Reiko; Hibino, Takeshi; Yoshida, Takayuki; Mukai, Seiji; Akita, Sachie; Yajima, Kazuhiro; Miyabe, Hiromichi; Goto, Toshihiko; Takada, Norio; Ohte, Nobuyuki; Kunimatu, Mitoshi; Kimura, Genjiro

2003-01-01

12

Determination of triglycerides with special emphasis on biosensors: a review.  

PubMed

Triglycerides (TG) are transesterification product of fatty acids and glycerol and engaged in the transportation of fats. Elevated triglyceride level is associated with coronary heart disease (CAD), atherosclerosis and hypolipoprotenemia. Convenient and reproducible assay systems based on enzymes are an attractive alternative to conventional analytical methods. Triglyceride biosensors (TGBs) are based on either measurement of oxygen consumed or electron generated from splitting of H2O2, an ultimate product, of immobilized enzymes. TGBs work optimally within 2-900 s, between pH 6.4-8.5 and the potential 0.5-4V. TGBs measure TG level in serum directly and can be used over a period of 14 to 168 days. This review describes the analytic characteristics of various methods available for determination of TGs with special emphasis on TGBs. PMID:23932946

Pundir, C S; Narang, Jagriti

2013-10-01

13

Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals  

PubMed Central

Background: The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to sCD36 among morbidly obese individuals. Furthermore, we investigated the levels of sCD36 in relation to obesity-related metabolic complications, low-grade inflammation and fat distribution. Methods: Twenty morbidly obese individuals (body mass index (BMI) 43.0±5.4?kg?m?2) with a referral to Roux-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model assessment (HOMA-%S) and liver fat percentage (LF%), respectively. Results: Postoperatively, BMI was reduced by 20% to 34.3±5.2?kg?m?2 (P<0.001). sCD36 was reduced by 31% (P=0.001) and improvements were observed in the amount of fat mass (P<0.001), truncal fat mass (P<0.001), circulating triglycerides (P=0.001), HOMA-%S (P=0.007), LF% (P=0.001) and the inflammatory marker high-sensitive C-reactive protein (P=0.005). sCD36 correlated with triglycerides (?=0.523, P=0.001) and truncal fat mass (?=0.357, P=0.026), and triglycerides were found to be an independent predictor of sCD36. At baseline, participants with the metabolic syndrome had a higher LF% and higher levels of the inflammatory biomarker YKL-40 (P=0.003 and P=0.014) as well as a tendency towards higher levels of sCD36. Conclusion: sCD36 was reduced by weight loss and associated with an unhealthy fat accumulation and circulating triglycerides, which support the proposed role of sCD36 as a biochemical marker of obesity-related metabolic complications and risks.

Kn?sgaard, L; Thomsen, S B; St?ckel, M; Vestergaard, H; Handberg, A

2014-01-01

14

Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death  

Microsoft Academic Search

Among the risk factors for coronary atherosclerosis, elevated LDL-C level is best known. The action of lipoprotein lipase on triglyceride-rich lipoproteins produces remnant lipoprotein particles enriched in cholesterol and apolipoprotein E (apo E). Apo E serves as the ligand for uptake of remnant lipoproteins via the LDL-receptor or the remnant receptor. In this study, postmortem plasma total cholesterol, triglycerides (TG),

Sanae Takeichi; Nobuhiro Yukawa; Yasuhiro Nakajima; Motoki Osawa; Takeshi Saito; Yoshihisa Seto; Takamitsu Nakano; Abby R. Saniabadi; Masakazu Adachi; Tao Wang; Katsuyuki Nakajima

1999-01-01

15

Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion  

Microsoft Academic Search

Plasma triglyceride levels are higher in nephrotic than in analbuminemic rats despite a similar increase in hepatic triglyceride secretion. The relative contributions of increased hepatic secretion of triglyceride (TG) and decreased TG catabolism to hypertriglyceridemia in the nephrotic syndrome, and their relationship to urinary protein loss and reduced plasma colloid osmotic pressure (?) remain unclear. We measured the activity of

Jaap A Joles; Caspaar Bijleveld; Arie van Tol; Math JH Geelen; Hein A Koomans; Jaap A Joles DVM

1995-01-01

16

A role of apolipoprotein D in triglyceride metabolism[S  

PubMed Central

Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression of apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical apolipoproteins that are mainly produced in the liver, apoD is an atypical apolipoprotein with broad tissue distribution. We show that circulating apoD is present mainly in HDL and, to a lesser extent, in LDL and VLDL and that its plasma levels were reduced in db/db mice with visceral obesity and altered lipid metabolism. Elevated apoD production, derived from adenovirus-mediated gene transfer, resulted in significant reduction in plasma triglyceride levels in mice. This effect was attributable to en­hanced LPL activity and improved catabolism of triglyceride-rich particles. In contrast, VLDL triglyceride production remained unchanged in response to elevated apoD production. These findings were recapitulated in high-fat–induced obese mice. Obese mice with elevated apoD production exhibited significantly improved triglyceride profiles, correlating with increased plasma LPL activity and enhanced postprandial fat tolerance. ApoD was shown to promote LPL-mediated hydrolysis of VLDL in vitro, correlating with its TG-lowering action in vivo. Apolipoprotein D plays a significant role in lipid metabolism. These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome.

Perdomo, German; Kim, Dae Hyun; Zhang, Ting; Qu, Shen; Thomas, Elizabeth A.; Toledo, Frederico G. S.; Slusher, Sandra; Fan, Yong; Kelley, David E.; Dong, H. Henry

2010-01-01

17

Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice  

PubMed Central

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2?/? mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2 - Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.

Snaith, Michael; Lindmark, Helena; Lundberg, Johanna; Ostlund-Lindqvist, Ann-Margret; Angelin, Bo; Rudling, Mats

2012-01-01

18

Triglyceride kinetics in fasted and fed E. coli septic rats  

SciTech Connect

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributed to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.

Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical Coll., Philadelphia, PA (United States))

1990-02-26

19

Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats  

SciTech Connect

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))

1990-04-01

20

Regulation of triglyceride metabolism by Angiopoietin-like proteins.  

PubMed

Plasma triglyceride concentrations are determined by the balance between production of the triglyceride-rich lipoproteins VLDL and chylomicrons in liver and intestine, and their lipoprotein lipase-mediated clearance in peripheral tissues. In the last decade, the group of Angiopoietin-like proteins has emerged as important regulators of circulating triglyceride (TG) levels. Specifically, ANGPTL3 and ANGPTL4 impair TG clearance by inhibiting lipoprotein lipase (LPL). Whereas ANGPTL4 irreversibly inactivates LPL by promoting conversion of active LPL dimers into inactive monomers, ANGPTL3 reversibly inhibits LPL activity. Studies using transgenic or knockout mice have clearly demonstrated the stimulatory effect of Angptl3 and Angptl4 on plasma TG, which is further supported by human genetic data including genome wide association studies. Whereas ANGPTL3 is mainly active in the fed state, ANGPTL4 is elevated by fasting and mediates fasting-induced changes in plasma TG and free fatty acid metabolism. Both proteins undergo oligomerization and are subject to proteolytic cleavage to generate N- and C-terminal fragments with highly divergent biological activities. Expression of ANGPTL3 is exclusive to liver and governed by the liver X receptor (LXR). In contrast, ANGPTL4 is expressed ubiquitously and under sensitive control of the Peroxisome proliferator-activated receptor (PPAR) family and fatty acids. Induction of ANGPTL4 gene expression by fatty acids and via PPARs is part of a feedback mechanism aimed at protecting cells against lipotoxicity. So far there is very little evidence that other ANGPTLs directly impact plasma lipoprotein metabolism. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22063269

Mattijssen, Frits; Kersten, Sander

2012-05-01

21

Genetic determinants of plasma triglycerides.  

PubMed

Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ?10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

Johansen, Christopher T; Kathiresan, Sekar; Hegele, Robert A

2011-02-01

22

Correlation of triglyceride level with acute coronary syndrome.  

PubMed

The study was aimed to find out the correlation of serum triglyceride level with acute coronary syndrome. This cross sectional study was conducted in the department of cardiology, Mymensingh Medical College Hospital, from August 2009 to May 2010. Socio-demographic characteristics, smoking habit, hypertension, serum total cholesterol level, serum HDLc, Serum LDLc, TG level were important variable considered. A total number of 100 respondents consisted of 50 cases (patient) and 50 healthy persons (control). Investigations included ECG, cardiac enzyme (troponin I), FBS and lipid profile. The data were analyzed by computer with the help of SPSS. Chi-square Test, T-test & ANOVA test were used as test of significance. The mean level of TG in acute coronary syndrome (ACS) patients (cases) was 168.2±58.0 mg/dl and in control were 141.2±45.3 mg/dl. So serum TG level is significantly higher in patients with ACS (p=0.01). In multivariate regression analysis, there was a significant association of elevated TG with risk of ACS (relative risk) is the highest, compared with the lowest quarantile = 1.011; 95% confidence interval (CI = 1.002 - 1.020; P for trend = 0.01). The relation of TG level to HDLc was a strong predictor of ACS (RR in the highest) compared with lowest quarantile = 0.02; (95% CI = 0.003 - 0.173; P for trend <0.0001). The study revealed that high level of serum triglyceride is associated with ACS. Categorization of patients with ACS on the basis of TG level may be helpful for risk stratification and management. PMID:22314453

Islam, M Z; Faruque, M; Bari, M A; Islam, M S; Khan, M K; Khan, N A; Miah, A H; Alam, M K

2012-01-01

23

Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling  

PubMed Central

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)+ mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg+ mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg+ mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg+ mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg+ mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg+ mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue.

Roohk, Donald J.; Fitch, Mark; Boudignon, Benjamin M.; Halloran, Bernard P.; Hellerstein, Marc K.

2013-01-01

24

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution  

PubMed Central

Objective To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. Methods Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Results Contents of pre?1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, pre?1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of pre?1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ? 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. Conclusions The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of pre?1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

2011-01-01

25

Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice  

PubMed Central

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO2 = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 = 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [3H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-?, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.

Shin, Mi-Kyung; Yao, Qiaoling; Bevans-Fonti, Shannon; Poole, James; Drager, Luciano F.; Polotsky, Vsevolod Y.

2012-01-01

26

Regulation of triglyceride metabolism by Angiopoietin-like proteins  

Microsoft Academic Search

Plasma triglyceride concentrations are determined by the balance between production of the triglyceride-rich lipoproteins VLDL and chylomicrons in liver and intestine, and their lipoprotein lipase-mediated clearance in peripheral tissues. In the last decade, the group of Angiopoietin-like proteins has emerged as important regulators of circulating triglyceride (TG) levels. Specifically, ANGPTL3 and ANGPTL4 impair TG clearance by inhibiting lipoprotein lipase (LPL).

Frits Mattijssen; Sander Kersten

27

Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease  

PubMed Central

Background Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results The minor allele of rs964184 was strongly associated with log plasma triglycerides (? 0.12; 95%CI 0.10-0.15, p?=?1.1*10?19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (? 0.02; (95%CI ?0.04–0.09) if body mass index <24 kg/m2, ? 0.17 (95%CI 0.12–0.22) if body mass index >27 kg/m2, p for interaction?=?0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p?=?0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients.

van de Woestijne, Anton P.; van der Graaf, Yolanda; de Bakker, Paul I. W.; Asselbergs, Folkert W.; Spiering, Wilko; Visseren, Frank L. J.

2014-01-01

28

Apo B secretion is regulated by hepatic triglyceride, and not insulin, in a model of increased hepatic insulin signaling  

PubMed Central

Objective States of insulin resistance, hyperinsulinemia, and hepatic steatosis are associated with increased secretion of triglycerides (TG) and apolipoprotein B (apoB), even though insulin targets apoB for degradation. We used hepatic-specific (h) Pten knockout (ko) mice, with increased hepatic insulin signaling, to determine the relative roles of insulin signaling and hepatic TG in regulating apoB secretion. Results/Methods TG and apoB secretion were elevated in hPten-ko mice. When hepatic TG was reduced by inhibition of DGAT1/DGAT2 or SREBP-1c, both TG and apoB secretion fell without changes in hepatic insulin signaling. Acute reconstitution of hPten reduced hepatic TG content and both TG and apoB secretion fell within 4 days despite decreased hepatic insulin signaling. Acute depletion of hepatic Pten by adenoviral introduction of Cre into Pten Floxed mice caused steatosis within 4 days, and secretion of TG and apoB both increased despite increased hepatic insulin signaling. Even when steatosis after acute Pten depletion was prevented by pre-treatment with SREBP-1c ASO, apoB secretion was not reduced after 4 days. Ex vivo results were in primary hepatocytes were similar. Conclusion Either hepatic TG is the dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin signaling on apoB secretion is very short-lived.

Moon, Byoung C.; Hernandez-Ono, Antonio; Stiles, Bangyan; Wu, Hong; Ginsberg, Henry N.

2013-01-01

29

Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease  

PubMed Central

Background The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n?=?103; High group ?1.2 mmol/L, n?=?226). The relationship between the TG levels and early outcomes were evaluated. Results High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P?=?0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions High level of fasting TG (?1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics.

2014-01-01

30

Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women.  

PubMed

Background/Objectives:Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits.Subjects/Methods:Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity.Results:Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29-14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 × 10(-2)). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (?80?cm) increased TG levels from 1.32 to 1.71?mmol?l(-1). However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels.Conclusions:The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease. PMID:24932782

Zubair, N; Mayer-Davis, E J; Mendez, M A; Mohlke, K L; North, K E; Adair, L S

2014-01-01

31

Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women  

PubMed Central

Background/Objectives: Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits. Subjects/Methods: Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity. Results: Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29–14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 × 10?2). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (?80?cm) increased TG levels from 1.32 to 1.71?mmol?l?1. However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels. Conclusions: The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease.

Zubair, N; Mayer-Davis, E J; Mendez, M A; Mohlke, K L; North, K E; Adair, L S

2014-01-01

32

Impact of lowering triglycerides on raising HDL-C in hypertriglyceridemic and non-hypertriglyceridemic subjects.  

PubMed

Although an inverse association between triglyceride (TG) and (HDL-C) is well documented, the impact of lowering TG on HDL-C levels has not been well established. Therefore, data were analyzed in 151 consecutive dyslipidemic patients who made multiple visits (n=1830) to the University of Maryland Preventive Cardiology Center between 1991 and 2005. At baseline, fasting TG levels at or above the median (178 mg/dL) were associated with significantly lower HDL-C than TG levels below the median (32.6+/-11.1 mg/dL versus 45.1+/-14.2 mg/dL; P<0.0001). Following baseline evaluation, various therapies were employed (i.e., dietary, exercise, medication) to reduce mean LDL (147.3+/-53.4 mg/dL) and TG (306.1+/-414.9 mg/dL). Using a fully adjusted mixed regression model, each 50 mg/dL reduction in TG was independently associated with a 0.5 mg/dL increase in HDL-C in hypertriglyceridemic subjects (e.g., TG> or =200 mg/dL) and a 1.7 mg/dL increase in HDL-C in the absence of elevated TG (P<0.0001). The use of niacin (P<0.0001), statins (P=0.0003) and fibrates (P=0.03) were also associated with significant increases in HDL-C beyond that anticipated with TG reduction. These data indicate that lowering TG is independently and inversely correlated with HDL-C, effects that are most pronounced in the absence of hypertriglyceridemia. PMID:17052787

Miller, Michael; Langenberg, Patricia; Havas, Stephen

2007-07-10

33

Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice  

Microsoft Academic Search

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob\\/ob mice treated with a specific inhibitor of Slc10a2. Plasma

Thomas Lundåsen; Eva-Marie Andersson; Michael Snaith; Helena Lindmark; Johanna Lundberg; Ann-Margret Östlund-Lindqvist; Bo Angelin; Mats Rudling

2012-01-01

34

Triglyceride is strongly associated with nonalcoholic fatty liver disease among markers of hyperlipidemia and diabetes  

PubMed Central

The aim of the present study was to reveal the metabolic disorders most commonly associated with nonalcoholic fatty liver disease (NAFLD). Triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), blood glucose (BG) and hemoglobin A1c (HbA1c) were analyzed. NAFLD was diagnosed using abdominal ultrasound (US), and TG, HDL, LDL, BG and HbA1c were immediately collected on the same day and subjected to multivariate regression analysis. Stepwise analysis was performed to select the variables that were closely associated with NAFLD. The patients who were positive for the hepatitis B antigen and hepatitis C antibody were excluded from the study. Additionally, the patients who were prescribed prednisolone or methotrexate were excluded from the study as these agents may cause NAFLD or liver toxicity. The study included 168 and 125 patients with and without NAFLD, respectively. TG, BG and HbA1c were strongly correlated with NAFLD. Among these parameters, TG was the strongest predictor of NAFLD (?2=9.89, P=0.0017). TG was the parameter that was most strongly associated with NAFLD. In conclusion, elevated TG was a marker of NAFLD.

TOMIZAWA, MINORU; KAWANABE, YUJI; SHINOZAKI, FUMINOBU; SATO, SUMIHIKO; MOTOYOSHI, YASUFUMI; SUGIYAMA, TAKAO; YAMAMOTO, SHIGENORI; SUEISHI, MAKOTO

2014-01-01

35

Modulation of plasma TG lipolysis by Angiopoietin-like proteins and GPIHBP1.  

PubMed

There is evidence that elevated plasma triglycerides (TG) serve as an independent risk factor for coronary heart disease. Plasma TG levels are determined by the balance between the rate of production of chylomicrons and VLDL in intestine and liver, respectively, and their rate of clearance in peripheral tissues. Lipolytic processing of TG-rich lipoproteins is mediated by the enzyme lipoprotein lipase (LPL), which is tethered to the capillary endothelium via heparin sulphate proteoglycans. In recent years the Angiopoietin-like proteins ANGPTL3 and ANGPTL4 have emerged as novel modulators of LPL activity. Studies in transgenic animals supported by in vitro experiments have demonstrated that ANGPTL3 and ANGPTL4 impair plasma TG clearance by inhibiting LPL activity. In humans, genetic variation within the ANGPTL3 and ANGPTL4 genes contributes to variation in plasma TG and HDL levels, thereby validating the importance of ANGPTLs in the regulation of lipoprotein metabolism in humans. Combined with the discovery of GPIHBP1 as a likely LPL anchor, these findings have led to a readjustment of the mechanism of LPL function. This review provides an overview of our current understanding of the role and regulation of ANGPTL3, ANGPTL4 and GPIHBP1, and places the newly acquired knowledge in the context of the established function and mechanism of LPL-mediated lipolysis. PMID:20056168

Lichtenstein, Laeticia; Kersten, Sander

2010-04-01

36

Direct Antidiabetic Effect of Leptin through Triglyceride Depletion of Tissues  

Microsoft Academic Search

Leptin is currently believed to control body composition largely, if not entirely, via hypothalamic receptors that regulate food intake and thermogenesis. Here we demonstrate direct extraneural effects of leptin to deplete fat content of both adipocytes and nonadipocytes to levels far below those of pairfed controls. In cultured pancreatic islets, leptin lowered triglyceride (TG) content by preventing TG formation from

Michio Shimabukuro; Kazunori Koyama; Guoxun Chen; May-Yun Wang; Falguni Trieu; Young Lee; Christopher B. Newgard; Roger H. Unger

1997-01-01

37

Increased plasma free fatty acid and triglyceride levels after single administation of toluene in rabbits  

SciTech Connect

Changes of plasma lipids (triglyceride, TG: total cholesterol, Cho; and phospholipids, PL), free fatty acid (FFA), and blood glucose (BG) were studied in male rabbits after toluene administration (0.5 g/kg per os). Hypertriglyceridemia was observed at and after 2 h. Plasma FFA and BG were elevated temporarily during the early stage and lowered gradually thereafter. Initially, plasma Cho and PL were virtually unchanged, by the Cho levels increased slowly after 6 h. The hypertriglyceridemia observed may have some adverse effects on heart function.

Takahashi, Setsunori; Tanabe, Koichi; Shiono, Hiroshi (Shimane Medical Univ., Izumo (Japan)); Maseda, Chikatoshi (Shimane Prefectural Police Headquarters, Matsue (Japan)); Fukui, Yuko (Kyoto Univ. (Japan))

1988-01-01

38

Differential uptake of subfractions of triglyceride-rich lipoproteins by THP1 macrophages  

Microsoft Academic Search

It is well known that raised plasma triglycerides (TG) are positively linked to the development of coronary heart disease. However, triglycerides circulate in a range of distinct lipoprotein subfractions and the relative atherogenicity of these subfractions is not clear. In this study, three fractions of triglyceride rich lipoprotein (TRL) were isolated from normolipidaemic males according to their differing Svedberg flotation

Anna M. Palmer; Esther Nova; Eliz Anil; Kim Jackson; Paul Bateman; Emma Wolstencroft; Christine M. Williams; Parveen Yaqoob

2005-01-01

39

Partially saponified triglyceride ethoxylates  

Microsoft Academic Search

Various triglycerides (coconut oil, palm kernel oil, tallow) were ethoxylated with a proprietary catalyst (calcium\\/aluminum\\u000a alkoxide complex partially neutralized in an alcohol ethoxylate base) to obtain triglyceride ethoxylates. Triglyceride ethoxylates\\u000a were then partially saponified with sodium hydroxide to form mixtures of mono-, di-, and triglyceride ethoxylates, fatty acid\\u000a soap, and glycerol ethoxylate. These mixtures were characterized in terms of physical

Michael F. Cox; Upali Weerassoriya

2000-01-01

40

Long-term fructose feeding changes the expression of leptin receptors and autophagy genes in the adipose tissue and liver of male rats: a possible link to elevated triglycerides.  

PubMed

Long-term fructose consumption has been shown to evoke leptin resistance, to elevate triglyceride levels and to induce insulin resistance and hepatic steatosis. Autophagy has been suggested to function in processes such as lipid storage in adipose tissue and inflammation in liver. Autophagy and the leptin system have also been suggested to regulate each other. This study aimed to identify the changes caused by fetal undernourishment and postnatal fructose diet in the gene expression of leptin, its receptors (LEPR-a, LEPR-b, LEPR-c, LEPR-e and LEPR-f) and autophagy genes in the white adipose tissue (WAT) and liver of adult male rats in order to clarify the mechanism behind the metabolic alterations. The data clearly revealed that the long-term postnatal fructose diet decreased leptin levels (p < 0.001), LEPR (p < 0.001), especially LEPR-b (p = 0.011) and LEPR-f (p = 0.005), as well as SOCS3 (p < 0.001), ACC (p = 0.006), ATG7 (p < 0.001), MAP1LC3? (p < 0.001) and LAMP2 (p = 0.004) mRNA expression in WAT. Furthermore, LEPR (p < 0.001), especially LEPR-b (p = 0.001) and LEPR-f (p < 0.001), ACC (p = 0.010), ATG7 (p = 0.024), MAP1LC3? (p = 0.003) and LAMP2 (p < 0.001) mRNA expression in the liver was increased in fructose-fed rats. In addition, the LEPR expression in liver and MAP1LC3? expression in WAT together explained 55.7 % of the variation in the plasma triglyceride levels of the rats (R adj. (2)  = 0.557, p < 0.001). These results, together with increased p62 levels in WAT (p < 0.001), could indicate decreased adipose tissue lipid storing capacity as well as alterations in liver metabolism which may represent a plausible mechanism through which fructose consumption could disturb lipid metabolism and result in elevated triglyceride levels. PMID:24085619

Aijälä, Meiju; Malo, Elina; Ukkola, Olavi; Bloigu, Risto; Lehenkari, Petri; Autio-Harmainen, Helena; Santaniemi, Merja; Kesäniemi, Y Antero

2013-11-01

41

Effect of raloxifene on serum triglycerides in postmenopausal women: influence of predisposing factors for hypertriglyceridemia  

Microsoft Academic Search

Background: Estrogen increases serum triglyceride (TG) levels and induces hypertriglyceridemia in susceptible women. The effect of raloxifene (RLX), a selective estrogen-receptor modulator, on serum TG has not been studied in detail.Objective: The purpose of this study was to examine the effect of RLX on serum TG levels in postmenopausal women with and without osteoporosis, including those with predisposing factors for

Lori Mosca; Kristine Harper; Somnath Sarkar; John O'Gorman; Pamela W. Anderson; David A. Cox; Elizabeth Barrett-Connor

2001-01-01

42

Determining hepatic triglyceride production in mice: comparison of poloxamer 407 with Triton WR-1339  

Microsoft Academic Search

Triglyceride (TG), a water-insoluble energy-rich lipid, is secreted by the liver as part of very low density lipo- proteins (VLDLs) to supply energy to extrahepatic tissues. Overproduction of VLDL is associated with increased risk of cardiovascular heart disease; this has renewed an interest in factors that affect hepatic TG production. The TG pro- duction rate is determined by measuring temporal

John S. Millar; Debra A. Cromley; Mary G. McCoy; Daniel J. Rader; Jeffrey T. Billheimer

2005-01-01

43

Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.  

PubMed

To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile. PMID:17179770

De Truchis, Pierre; Kirstetter, Myriam; Perier, Antoine; Meunier, Claire; Zucman, David; Force, Gilles; Doll, Jacques; Katlama, Christine; Rozenbaum, Willy; Masson, Hélène; Gardette, Jean; Melchior, Jean-Claude

2007-03-01

44

The role of triglycerides in atherosclerosis.  

PubMed

Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular exercise. High-risk patients with hypertriglyceridemia, such as those with diabetes, CVD, or metabolic syndrome, may benefit from additional drug treatment aside from a statin to address other lipid abnormalities. In this discussion, we review the role of hypertriglyceridemia and its associated atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of a high TG level as a predictor of CVD, the cardiovascular outcomes from TG-lowering intervention trials, and the current guidelines for treating hypertriglyceridemia. PMID:21968696

Talayero, Beatriz G; Sacks, Frank M

2011-12-01

45

The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment  

Microsoft Academic Search

Metabolic response to the triglyceride (TG)-lowering drug, fenofibrate, is shaped by interactions between genetic and environmental factors, yet knowledge regarding the genetic determinants of this response is primarily limited to single-gene effects. Since very low-density lipoprotein (VLDL) is the central carrier of fasting TG, identifying factors that affect both total TG and VLDL–TG response to fenofibrate is critical for predicting

Jennifer A Smith; Donna K Arnett; Reagan J Kelly; Jose M Ordovas; Yan V Sun; Paul N Hopkins; James E Hixson; Robert J Straka; James M Peacock; Sharon L R Kardia

2008-01-01

46

Postprandial metabolism of meal triglyceride in humans*,**  

PubMed Central

The intake of dietary fat above energy needs has contributed to the growing rates of obesity worldwide. The concept of disease development occurring in the fed state now has much support and dysregulation of substrate flux may occur due to poor handling of dietary fat in the immediate postprandial period. The present paper will review recent observations implicating cephalic phase events in the control of enterocyte lipid transport, the impact of varying the composition of meals on subsequent fat metabolism, and the means by which dietary lipid carried in chylomicrons can lead to elevated postprandial non-esterified fatty acid concentrations. This discussion is followed by an evaluation of the data on quantitative meal fat oxidation at the whole body level and an examination of dietary fat clearance to peripheral tissues — with particular attention paid to skeletal muscle and liver given the role of ectopic lipid deposition in insulin resistance. Estimates derived from data of dietary-TG clearance show good agreement with clearance to the liver equaling 8–12% of meal fat in lean subjects and this number appears higher (10–16%) in subjects with diabetes and fatty liver disease. Finally, we discuss new methods with which to study dietary fatty acid partitioning in vivo. Future research is needed to include a more comprehensive understanding of 1) the potential for differential oxidation of saturated versus unsaturated fatty acids which might lead to meaningful energy deficit and whether this parameter varies based on insulin sensitivity, 2) whether compartmentalization exists for diet-derived fatty acids within tissues vs. intracellular pools, and 3) the role of reduced peripheral fatty acid clearance in the development of fatty liver disease. Further advancements in the quantitation of dietary fat absorption and disposal will be central to the development of therapies designed to treat diet-induced obesity. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

Lambert, Jennifer E.; Parks, Elizabeth J.

2012-01-01

47

Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo.  

PubMed

Patients at increased cardiovascular risk commonly display high levels of plasma triglycerides (TGs), elevated LDL cholesterol, small dense LDL particles and low levels of HDL-cholesterol. Many remain at high risk even after successful statin therapy, presumably because TG levels remain high. Lipoprotein lipase (LPL) maintains TG homeostasis in blood by hydrolysis of TG-rich lipoproteins. Efficient clearance of TGs is accompanied by increased levels of HDL-cholesterol and decreased levels of small dense LDL. Given the central role of LPL in lipid metabolism we sought to find small molecules that could increase LPL activity and serve as starting points for drug development efforts against cardiovascular disease. Using a small molecule screening approach we have identified small molecules that can protect LPL from inactivation by the controller protein angiopoietin-like protein 4 during incubations in vitro. One of the selected compounds, 50F10, was directly shown to preserve the active homodimer structure of LPL, as demonstrated by heparin-Sepharose chromatography. On injection to hypertriglyceridemic apolipoprotein A-V deficient mice the compound ameliorated the postprandial response after an olive oil gavage. This is a potential lead compound for the development of drugs that could reduce the residual risk associated with elevated plasma TGs in dyslipidemia. PMID:24984153

Larsson, Mikael; Caraballo, Rémi; Ericsson, Madelene; Lookene, Aivar; Enquist, Per-Anders; Elofsson, Mikael; Nilsson, Stefan K; Olivecrona, Gunilla

2014-07-25

48

Metformin lowers plasma triglycerides by promoting VLDL-triglyceride clearance by brown adipose tissue in mice.  

PubMed

Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism. We found that metformin markedly lowered plasma total cholesterol and TG levels, an effect mostly due to a decrease in VLDL-TG, whereas HDL was slightly increased. Strikingly, metformin did not affect hepatic VLDL-TG production, VLDL particle composition, and hepatic lipid composition but selectively enhanced clearance of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles into brown adipose tissue (BAT). BAT mass and lipid droplet content were reduced in metformin-treated mice, pointing to increased BAT activation. In addition, both AMP-activated protein kinase ?1 (AMPK?1) expression and activity and HSL and mitochondrial content were increased in BAT. Furthermore, therapeutic concentrations of metformin increased AMPK and HSL activities and promoted lipolysis in T37i differentiated brown adipocytes. Collectively, our results identify BAT as an important player in the TG-lowering effect of metformin by enhancing VLDL-TG uptake, intracellular TG lipolysis, and subsequent mitochondrial fatty acid oxidation. Targeting BAT might therefore be considered as a future therapeutic strategy for the treatment of dyslipidemia. PMID:24270984

Geerling, Janine J; Boon, Mariëtte R; van der Zon, Gerard C; van den Berg, Sjoerd A A; van den Hoek, Anita M; Lombès, Marc; Princen, Hans M G; Havekes, Louis M; Rensen, Patrick C N; Guigas, Bruno

2014-03-01

49

Triglyceride-lowering agents.  

PubMed

This review is the first attempt at systematization of the literature data on the structures and activities of triglyceride-lowering agents which used in medical practice or are in development. The effects and mechanisms of action of statins, squalene synthase inhibitors, fibrates, PPAR? and PPAR?/? agonists, nicotinic acid, omega-3 fatty acids and some other molecular targets were considered. Unfortunately, to date, harmless and effective triglyceride-lowering drug still does not exist and there is still need for development of better triglyceride-lowering agents. PMID:24894768

Salakhutdinov, Nariman F; Laev, Sergey S

2014-07-15

50

Inhibition of Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT2) Prevents Dietary Cholesterol-associated Steatosis by Enhancing Hepatic Triglyceride Mobilization*  

PubMed Central

Acyl-CoA:cholesterol O-acyl transferase 2 (ACAT2) promotes cholesterol absorption by the intestine and the secretion of cholesteryl ester-enriched very low density lipoproteins by the liver. Paradoxically, mice lacking ACAT2 also exhibit mild hypertriglyceridemia. The present study addresses the unexpected role of ACAT2 in regulation of hepatic triglyceride (TG) metabolism. Mouse models of either complete genetic deficiency or pharmacological inhibition of ACAT2 were fed low fat diets containing various amounts of cholesterol to induce hepatic steatosis. Mice genetically lacking ACAT2 in both the intestine and the liver were dramatically protected against hepatic neutral lipid (TG and cholesteryl ester) accumulation, with the greatest differences occurring in situations where dietary cholesterol was elevated. Further studies demonstrated that liver-specific depletion of ACAT2 with antisense oligonucleotides prevents dietary cholesterol-associated hepatic steatosis both in an inbred mouse model of non-alcoholic fatty liver disease (SJL/J) and in a humanized hyperlipidemic mouse model (LDLr?/?, apoB100/100). All mouse models of diminished ACAT2 function showed lowered hepatic triglyceride concentrations and higher plasma triglycerides secondary to increased hepatic secretion of TG into nascent very low density lipoproteins. This work demonstrates that inhibition of hepatic ACAT2 can prevent dietary cholesterol-driven hepatic steatosis in mice. These data provide the first evidence to suggest that ACAT2-specific inhibitors may hold unexpected therapeutic potential to treat both atherosclerosis and non-alcoholic fatty liver disease.

Alger, Heather M.; Brown, J. Mark; Sawyer, Janet K.; Kelley, Kathryn L.; Shah, Ramesh; Wilson, Martha D.; Willingham, Mark C.; Rudel, Lawrence L.

2010-01-01

51

Stereospecific analysis of triglycerides  

Microsoft Academic Search

Stereospecific analysis determines how the fatty acids of triglycerides are distributed over the three different positions\\u000a of the glycerol. The special problem is the differentiation of position I-1 and L-3 of glycerol. In the presently known methods,\\u000a triglycerides are first degraded to mixtures of diglycerides, either by the action of a lipase or by degradation with a Grignard\\u000a reagent. The

H. Brockerhoff

1971-01-01

52

Myocardial triglycerides: magnetic resonance spectroscopy in health and diabetes  

Microsoft Academic Search

In this thesis we focused on the functional and metabolic consequences of myocardial triglyceride (TG) accumulation in healthy subjects and in patients with diabetes mellitus. Ectopic accumulation of TGs is associated with organ dysfunction in metabolic disease in experimental animal studies. These organs include the heart, the liver and skeletal muscle. For the heart,translational studies in humans are scarce, mainly

Sebastiaan Hammer

2008-01-01

53

Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet  

PubMed Central

Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-?B activity but also reduces hypertriglyceridemia in humans. The aim of this study was to investigate the mechanism by which aspirin improves hypertriglyceridemia. Human apolipoprotein CI (apoCI)-expressing mice (APOC1 mice), an animal model with elevated plasma triglyceride (TG) levels, as well as normolipidemic wild-type (WT) mice were fed a high-fat diet (HFD) and treated with aspirin. Aspirin treatment reduced hepatic NF-?B activity in HFD-fed APOC1 and WT mice, and in addition, aspirin decreased plasma TG levels (?32%, P < 0.05) in hypertriglyceridemic APOC1 mice. This TG-lowering effect could not be explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic production of VLDL-TG in both APOC1 (?28%, P < 0.05) and WT mice (?33%, P < 0.05) without affecting VLDL-apoB production. Aspirin did not alter hepatic expression of genes involved in FA oxidation, lipogenesis, and VLDL production but decreased the incorporation of plasma-derived FA by the liver into VLDL-TG (?24%, P < 0.05), which was independent of hepatic expression of genes involved in FA uptake and transport. We conclude that aspirin improves hypertriglyceridemia by decreasing VLDL-TG production without affecting VLDL particle production. Therefore, the inhibition of inflammatory pathways by aspirin could be an interesting target for the treatment of hypertriglyceridemia.

Vroegrijk, Irene O. C. M.; Berbee, Jimmy F. P.; Shoelson, Steven E.; Romijn, Johannes A.; Havekes, Louis M.; Rensen, Patrick C. N.; Voshol, Peter J.

2011-01-01

54

Defective insulin signaling in skeletal muscle of the hypertensive TG(mREN2)27 rat.  

PubMed

Essential hypertension is frequently associated with insulin resistance of skeletal muscle glucose transport, with a potential role of angiotensin II in the pathogenesis of both conditions. The male heterozygous TG(mREN2)27 rat harbors the mouse transgene for renin, exhibits local elevations in angiotensin II, and is an excellent model of both hypertension and insulin resistance. The present study was designed to investigate the potential cellular mechanisms for insulin resistance in this hypertensive animal model, including an assessment of elements of the insulin-signaling pathway. Compared with nontransgenic, normotensive Sprague-Dawley control rats, male heterozygous TG(mREN2)27 rats displayed elevated (P < 0.05) fasting plasma insulin (74%), an exaggerated insulin response (108%) during an oral glucose tolerance test, and reduced whole body insulin sensitivity. TG(mREN2)27 rats also exhibited decreased insulin-mediated glucose transport and glycogen synthase activation in both the type IIb epitrochlearis (30 and 46%) and type I soleus (22 and 64%) muscles. Importantly, there were significant reductions (approximately 30-50%) in insulin stimulation of tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1), IRS-1 associated with the p85 subunit of phosphatidylinositol 3-kinase, Akt Ser473 phosphorylation, and Ser9 phosphorylation of glycogen synthase kinase-3beta in epitrochlearis and soleus muscles of TG(mREN2)27 rats. Soleus muscle triglyceride concentration was 25% greater in the transgenic group compared with nontransgenic animals. Collectively, these data provide the first evidence that the insulin resistance of the hypertensive male heterozygous TG(mREN2)27 rat can be attributed to specific defects in the insulin-signaling pathway in skeletal muscle. PMID:15657091

Sloniger, Julie A; Saengsirisuwan, Vitoon; Diehl, Cody J; Dokken, Betsy B; Lailerd, Narissara; Lemieux, Andrew M; Kim, John S; Henriksen, Erik J

2005-06-01

55

Positive relationship between dietary fat, ethanol intake, triglycerides and hypothalamic peptides: Counteraction by lipid-lowering drugs  

PubMed Central

Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TG), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TG and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected with ethanol (1 g/kg i.p.) and tested in terms of their preference for a high-fat compared to low-fat diet, showed a significant increase in their fat preference, compared to rats injected with saline, in measures of 2 h and 24 h intake. Experiment 2 tested the relationship of circulating TG in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol vs. water and given acute meal tests (25 kcal) of a high-fat vs. low-fat diet. Levels of TG were elevated in response to both chronic drinking of ethanol vs. water and acute eating of a high-fat vs. low-fat meal. Most importantly, ethanol and a high-fat diet showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a low-fat diet (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After administration of gemfibrozil (50 mg/kg i.g.) compared to vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide OX, in the perifornical lateral hypothalamus. These results support the existence of a vicious cycle between ethanol and fat whereby each nutrient stimulates intake of the other. Within this vicious cycle, ethanol and fat act synergistically to increase TG levels, which in turn stimulate peptides that promote further consumption, and these phenomena are reversed by gemfibrozil, which lowers TG levels.

Barson, Jessica R.; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F.; Bocarsly, Miriam E.; Hoebel, Bartley G.; Leibowitz, Sarah F.

2009-01-01

56

Carbohydrate-Induced Hypertriglyceridemia: An Insight into the Link between Plasma Insulin and Triglyceride Concentrations  

Microsoft Academic Search

This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or

T. MCLAUGHLIN; F. ABBASI; C. LAMENDOLA; H. YENI-KOMSHIAN; G. REAVEN

2009-01-01

57

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution  

Microsoft Academic Search

OBJECTIVE: To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. METHODS: Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. RESULTS:

Li Tian; Yanhua Xu; Mingde Fu; Tao Peng; Yinghui Liu; Shiyin Long

2011-01-01

58

Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects  

Microsoft Academic Search

Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it

D. I. W. Phillips; S. Caddy; V. Ilic; B. A. Fielding; K. N. Frayn; A. C. Borthwick; R. Taylor

1996-01-01

59

Serum cholesterol and triglyceride measurements in Canadian physicians.  

PubMed Central

In a study of serum cholesterol and triglyceride concentrations in male physicians, blood was drawn after fasting from 2071 registrants at 17 Canadian medical meetings from 1968 to 1973. Eight regional medical laboratories participated in the study. About two thirds of the samples were analysed in one of two laboratories to diminish method variations. When chylomicronemia, hyperglycemia or extremely high triglyceride values were detected, suggesting nonfasting, the data were discarded. The mean serum cholesterol value for the total study population was 233.9 plus or minus 1.22 mg/dl and the mean serum triglyceride value, 150.5 plus or minus 2.48 mg/dl. The mean values and the prevalence of elevated values (cholesterol larger than or equal to 250 mg/dl; triglyceride larger than or equal to 150 mg/dl) were related to age. Of the total study population 34.7% had elevated cholesterol values and 36.2% had elevated triglyceride values; only the cholesterol value was elevated in 17.5%, only the triglyceride value in 19.6% and both values were elevated in 16.8%. Although this was not a random sampling of Canadian physicians or of Canadian men, our findings of elevated serum lipid values were similar to those in French Canadian civic workers, American executives and Scandinavians, and somewhat higher than those in the Albany, New York and Framingham populations, but distinctly higher than those reported by a recent Nutrition Canada survey.

Merriman, J. E.; Davies, R. O.

1975-01-01

60

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.  

PubMed

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even if significantly, higher TG levels in patients with CAD) and low-density lipoprotein cholesterol levels near optimal values. Nevertheless, patients with CAD had significantly lower high-density lipoprotein cholesterol, smaller low-density lipoprotein peak particle size, and a reduced HDL2b subfraction than controls. In addition, we observed higher concentrations of total TRL in patients with CAD together with a selective increase in apoE-rich particles. All these data were confirmed after correction for TG levels. We also investigated which parameters were associated with the spread of coronary atherosclerosis. Subjects with a single-vessel disease had selectively lower levels of apoE-rich fractions than patients with a multivessel disease. This was confirmed by multivariate analysis. Patients with a premature CAD free of nonlipid conventional risk factors, despite not having elevated lipid levels, show several lipoprotein abnormalities. Besides known atherogenic alterations, the accumulation of apoE-rich TRL subfractions may represent an additive factor that can potentially promote and initiate the atherosclerotic process. PMID:16631444

Barbagallo, Carlo M; Rizzo, Manfredi; Noto, Davide; Frasheri, Arian; Pernice, Vincenzo; Rubino, Antonio; Pieri, Daniele; Pinto, Vito; Cefalù, Angelo B; Giordano, Carla; Notarbartolo, Alberto; Averna, Maurizio R

2006-05-01

61

Effects of apolipoprotein A5 haplotypes on the ratio of triglyceride to high-density lipoprotein cholesterol and the risk for metabolic syndrome in Koreans  

PubMed Central

Background Single-nucleotide polymorphisms (SNPs) around the apolipoprotein A5 gene (APOA5) have pleiotropic effects on the levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). APOA5 SNPs have also been associated with metabolic syndrome (MS). Here, we constructed haplotypes with SNPs spanning APOA5 and ZNF259, which are approximately 1.3 kb apart, to perform association analyses with the risk for MS and the levels of TG and HDL-C in terms of a TG:HDL-C ratio. Methods The effects of three constructed haplotypes (TAA, CGG, and CGA, in the order of rs662799, rs651821, and rs6589566) on the TG:HDL-C ratio and MS were estimated using multiple regression analyses in 2,949 Koreans and in each gender separately (1,082 men and 1,867 women). Results The haplotypes, CGG and CGA, were associated with the TG:HDL-C ratio and the risk of MS development in both genders. That is, the minor alleles of the rs662799 and rs651821 in APOA5, irrespective of which allele was present at rs6589566, had the marked effects. Interestingly, a C–G–A haplotype at these three SNPs had the most marked effects on the TG:HDL-C ratio and the risk of MS development in women. Conclusions We have identified the novel APOA5-ZNF259 haplotype manifesting sex-dependent effects on elevation of the TG:HDL-C ratio as well as the increased risk for MS.

2014-01-01

62

Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response to fenofibric acid therapy in individuals with mixed dyslipidemia  

PubMed Central

Objective Individuals with mixed dyslipidemia have elevated triglycerides (TG), low high-density lipo-protein cholesterol (HDL-C), and increased risk for coronary disease. Fibrate therapy is commonly used to lower TG and increase HDL-C. Common genetic variants are known to affect the response to fibrate therapy. We sought to identify rare genetic variants (frequency ? 1%) in genes involved in TG and HDL-C metabolism that affect the response to fenofibric acid (FA) therapy. Methods Four genes with a major role in HDL-C and TG metabolism APOA1, APOC2, APOC-III and LPL were sequenced in 2385 participants with mixed dyslipidemia in a randomized, double-blind, active-controlled study comparing therapy with FA alone, in combination with statins, or statin alone. Rare variants collapsing or SKAT methods were used for the analysis. Results Synonymous rare variants in the LPL gene were significantly associated with absolute HDL-C change (P = 9 × 10?4) and TG percent change (P = 6.76 × 10?4) in those treated with FA only. Participants with these rare variants had a 2 mg/dL increase in HDL-C and 39 mg/dL decrease in TG as compared to 6.2 mg/dL increase in HDL-C and 100 mg/dL decrease in TG in those without these variants. Rare variants in the APOC-III gene were associated with a modest 3 mg/dL less reduction in APOB (P = 8.72 × 10?4) in those receiving FA and statin. Conclusion In individuals with mixed dyslipidemia rare synonymous variants within LPL gene were associated with attenuated response to FA therapy while APOCIII rare variants were associated with a modest effect on APOB response to FA-statin therapy. These results should be replicated in a similar clinical trial for further confirmation.

Gao, Feng; Ballantyne, Christie; Ma, Li; Virani, Salim S.; Keinan, Alon; Brautbar, Ariel

2014-01-01

63

Triglycerides and atherogenic lipoproteins: rationale for lipid management  

Microsoft Academic Search

Epidemiologic and clinical studies have demonstrated a relation between plasma triglyceride levels and risk of coronary artery disease and an amplification of risk with combined elevations of triglyceride and low-density lipoprotein (LDL) cholesterol. In patients with coronary disease, angiographic progression and clinical events have been correlated with concentrations of smaller very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), consistent with evidence

Ronald M. Krauss

1998-01-01

64

Gut triglyceride production  

PubMed Central

Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption.

Pan, Xiaoyue; Hussain, M. Mahmood

2012-01-01

65

Lipoprotein lipase deficiency is associated with elevated acylation stimulating protein plasma levels.  

PubMed

Acylation stimulating protein (ASP, C3adesArg) is an adipose tissue derived hormone that stimulates triglyceride (TG) synthesis. ASP stimulates lipoprotein lipase (LPL) activity by relieving feedback inhibition caused by fatty acids (FA). The present study examines plasma ASP and lipids in male and female LPL-deficient subjects primarily with the P207L mutation, common in the population of Quebec, Canada. We evaluated the fasting and postprandial states of LPL heterozygotes and fasting levels in LPL homozygotes. Homozygotes displayed increased ASP (58-175% increase, P < 0.05-0.01), reduced HDL-cholesterol (64-75% decrease, P < 0.0001), and elevated levels of TG (19-38-fold, P < 0.0001) versus control (CTL) subjects. LPL heterozygotes with normal fasting TG (1.3-1.9 mmol/l) displayed increased ASP (101-137% increase, P < 0.05-0.01) and delayed TG clearance after a fatload; glucose levels remained similar to controls. Hypertriglyceridemics with no known LPL mutation also had increased ASP levels (63-192% increase, P < 0.001). High-TG LPL heterozygotes were administered a fatload before and after fibrate treatment. The treatment reduced fasting and postprandial plasma ASP, TG, and FA levels without changing insulin or glucose levels. ASP enhances adipose tissue fatty-acid trapping following a meal; however in LPL deficiency, high ASP levels are coupled with delayed lipid clearance. PMID:19237736

Paglialunga, Sabina; Julien, Pierre; Tahiri, Youssef; Cadelis, Francois; Bergeron, Jean; Gaudet, Daniel; Cianflone, Katherine

2009-06-01

66

Lipoprotein lipase deficiency is associated with elevated acylation stimulating protein plasma levels  

PubMed Central

Acylation stimulating protein (ASP, C3adesArg) is an adipose tissue derived hormone that stimulates triglyceride (TG) synthesis. ASP stimulates lipoprotein lipase (LPL) activity by relieving feedback inhibition caused by fatty acids (FA). The present study examines plasma ASP and lipids in male and female LPL-deficient subjects primarily with the P207L mutation, common in the population of Quebec, Canada. We evaluated the fasting and postprandial states of LPL heterozygotes and fasting levels in LPL homozygotes. Homozygotes displayed increased ASP (58–175% increase, P < 0.05–0.01), reduced HDL-cholesterol (64–75% decrease, P < 0.0001), and elevated levels of TG (19–38-fold, P < 0.0001) versus control (CTL) subjects. LPL heterozygotes with normal fasting TG (1.3–1.9 mmol/l) displayed increased ASP (101–137% increase, P < 0.05–0.01) and delayed TG clearance after a fatload; glucose levels remained similar to controls. Hypertriglyceridemics with no known LPL mutation also had increased ASP levels (63–192% increase, P < 0.001). High-TG LPL heterozygotes were administered a fatload before and after fibrate treatment. The treatment reduced fasting and postprandial plasma ASP, TG, and FA levels without changing insulin or glucose levels. ASP enhances adipose tissue fatty-acid trapping following a meal; however in LPL deficiency, high ASP levels are coupled with delayed lipid clearance.

Paglialunga, Sabina; Julien, Pierre; Tahiri, Youssef; Cadelis, Francois; Bergeron, Jean; Gaudet, Daniel; Cianflone, Katherine

2009-01-01

67

Causes of the triglyceride-lowering effect of exercise training in rats  

NASA Technical Reports Server (NTRS)

Studies conducted with human subjects and laboratory animals have consistently shown a reduction in serum triglyceride (TG) in exercise-trained subjects. The obtained data have suggested that this decrease was due to a reduction in hepatic TG secretion. The present investigation, which was conducted with rats trained to attain a high level of spontaneous running activity, provides support for the earlier results. In addition, insights are obtained regarding the mechanism by which exercise lowers TG levels. Since the liver accounts for the vast majority of endogenous very low density lipoprotein (VLDL)-TG secretion, the fall in TG secretion rate seen in exercise-trained (ET) rats must be due to a reduction in hepatic TG secretion.

Mondon, C. E.; Dolkas, C. B.; Tobey, T.; Reaven, G. M.

1984-01-01

68

Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women.  

PubMed

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged ? 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P ? 0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity. PMID:21776016

Tohidi, M; Hatami, M; Hadaegh, F; Azizi, F

2012-09-01

69

The effect of insulin resistance on postprandial triglycerides in Korean type 2 diabetic patients.  

PubMed

We hypothesized that the influence of metabolic parameters depends on metabolic syndrome (MetS) status. The clinical and metabolic implications of postprandial triglyceride (ppTG) in Korean type 2 diabetes were investigated in the presence or absence of MetS, MetS+, or MetS-. To investigate the relationship between ppTG and metabolic parameters, we analyzed plasma TG levels in 126 newly diagnosed, drug-naïve diabetic patients after ingestion of a standardized low calorie and fat (500 kcal, 17.5 g fat) liquid meal formula. We report that MetS+ patients have significantly higher BMI, waist/hip ratio, HOMA-IR, and HOMA-?, but insignificantly higher fasting TG, ppTG, and ?TG than MetS- patients. In the MetS+ patients, ppTG correlated with fasting TG and non-HDL, but was not related to HOMA-IR. In MetS- patients, ppTG correlated with fasting TG, non-HDL, blood pressure, waist/hip ratio, fasting C-peptide and insulin levels, and HOMA-IR. Multivariate analysis showed HOMA-IR to be a predictive factor for ppTG in MetS- patients but not in MetS+ patients. ppTG correlated with IR in MetS- type 2 diabetic patients but not in MetS+. This unexpected result implies that MetS+ diabetic patients already have high fasting TG and that IR influences fasting TG more dominantly than ppTG. PMID:22854916

Park, Kyeong Hye; Kim, Kwang Joon; Lee, Byung-Wan; Kang, Eun Seok; Cha, Bong Soo; Lee, Hyun Chul

2014-02-01

70

Effect of Dietary Carbohydrate on Triglyceride Metabolism in Humans1  

Microsoft Academic Search

When the content of dietary carbohydrate is elevated above the level typically consumed (.55% of energy), blood concentrations of triglycerides rise. This phenomenon, known as carbohydrate-induced hypertri- glyceridemia, is paradoxical because the increase in dietary carbohydrate usually comes at the expense of dietary fat. Thus, when the content of the carbohydrate in the diet is increased, fat in the diet

Elizabeth J. Parks

71

Triglyceride accumulation and fatty acid profile changes in Chlorella (Chlorophyta) during high pH-induced cell cycle inhibition  

SciTech Connect

Alkaline pH stress resulted in triglyceride (TG) accumulation in Chlorella CHLOR1 and was independent of medium nitrogen or carbon levels. Based on morphological observations, alkaline pH inhibited autospore release, thus increasing the time for cell cycle completion. Autospore release has been postulated to coincide with TG utilization within the microalgal cell division cycle. The alkaline pH stress affected lipid accumulation by inhibiting the cell division cycle prior to autospore release and, therefore, prior to TG utilization. Cells inhibited in this manner showed an increase in TG accumulation but a decrease in both membrane lipid classes (glycolipid and polar lipid). Unlike TG fatty acid profiles, membrane lipid fatty acid profiles were not stable during TG accumulation. The membrane profiles became similar to the TG, i.e. less unsaturated than in the membrane lipids of unstressed control cells.

Guckert, J.B.; Cooksey, K.E. (Montana State Univ., Bozeman (USA))

1990-03-01

72

Masoprocol decreases serum triglyceride concentrations in rats with fructose-induced hypertriglyceridemia  

Microsoft Academic Search

Historically, extracts of the creosote bush have been used by native healers of the Southwest region of North America to treat symptoms of type 2 diabetes. More recently, we have shown that masoprocol (nordihydroguaiaretic acid), a pure compound isolated from the creosote bush (Larrea tridentata), decreases serum glucose and triglyceride (TG) levels when administered orally in rodent models of type

Karen A. Scribner; Theresa M. Gadbois; Maya Gowri; Salman Azhar; Gerald M. Reaven

2000-01-01

73

Chronic changes in plasma triglyceride levels do modify platelet membrane microviscosity in rats  

Microsoft Academic Search

Lipid metabolism disorders were proposed to mediate numerous cell membrane alterations in various forms of hypertension. Elevated plasma triglycerides were found to be associated with changes in membrane structure and function related to altered microviscosity in particular domains of the cell membrane. The aim of our study was to determine if an abnormal triglyceride metabolism might play a causal role

Jaroslav Kuneš; Marie-Aude Devynck; Josef Zicha

2000-01-01

74

Similar VLDL-TG Storage in Visceral and Subcutaneous Fat in Obese and Lean Women  

PubMed Central

OBJECTIVE Excess visceral fat accumulation is associated with the metabolic disturbances of obesity. Differential lipid redistribution through lipoproteins may affect body fat distribution. This is the first study to investigate VLDL-triglyceride (VLDL-TG) storage in visceral fat. RESEARCH DESIGN AND METHODS Nine upper-body obese (UBO; waist circumference >88 cm) and six lean (waist circumference <80 cm) women scheduled for elective tubal ligation surgery were studied. VLDL-TG storage in visceral, upper-body subcutaneous (UBSQ), and lower-body subcutaneous (LBSQ) fat were measured with [9,10-3H]-triolein–labeled VLDL. RESULTS VLDL-TG storage in visceral fat accounted for only ?0.8% of VLDL-TG turnover in UBO and lean women, respectively. A significantly larger proportion of VLDL-TG turnover was stored in UBSQ (?5%) and LBSQ (?4%) fat. The VLDL-TG fractional storage was similar in UBO and lean women for all regional depots. VLDL-TG fractional storage and VLDL-TG concentration were correlated in UBO women in UBSQ fat (r = 0.68, P = 0.04), whereas an inverse association was observed for lean women in visceral (r = ?0.89, P = 0.02) and LBSQ (r = ?0.87, P = 0.02) fat. CONCLUSIONS VLDL-TG storage efficiency is similar in all regional fat depots, and trafficking of VLDL-TG into different adipose tissue depots is similar in UBO and lean women. Postabsorptive VLDL-TG storage is unlikely to be of major importance in the development of preferential upper-body fat distribution in obese women.

S?ndergaard, Esben; Nellemann, Birgitte; S?rensen, Lars P.; Gormsen, Lars C.; Christiansen, Jens S.; Ernst, Erik; Dueholm, Margit; Nielsen, S?ren

2011-01-01

75

Identification of a novel locus for triglyceride on chromosome 1p31-32 in families with premature CAD and MI  

Microsoft Academic Search

An increased plasma triglyceride (TG) level is as- sociated with coronary artery disease (CAD) and myocardial infarction (MI) and is a key characteristic of the metabolic syndrome. Here, we used a genome-wide linkage scan to identify a novel genetic locus that influences the plasma TG level. We genotyped 714 persons in 388 multiplex Caucasian families with premature CAD and MI

Sara Bretschger Seidelmann; Lin Li; Gong-Qing Shen; Eric J. Topol; Qing Kenneth Wang

2008-01-01

76

Chylomicron metabolism in rats: lipolysis, recirculation of triglyceride-derived fatty acids in plasma FFA, and fate of core lipids as analyzed by compartmental modelling  

Microsoft Academic Search

Chylomicrons labeled in vivo with (%)oleic acid (primarily in triglycerides (TG), providing a tracer for lipolysis) and (SHIretinol (primarily in ester form, providing a tracer for the corelipids) were injectedinto rats. Disappearance ofthe two labels from plasma and appearance of label in plasma free fatty acids (FFA) were analyzed by compartmental modelling. Both coreandTG labeldistributedinto anapparent volume 10-15% larger than

Magnus Hultin; Roger Savonen; Thomas Olivecronal

77

Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).  

PubMed

AMR101 is an ?-3 fatty acid agent containing ?96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid. The efficacy and safety of AMR101 were evaluated in this phase 3, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial (ANCHOR) in high-risk statin-treated patients with residually high triglyceride (TG) levels (?200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (?40 and <100 mg/dl). Patients (n = 702) on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p <0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p <0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-low-density lipoprotein cholesterol (24.4%), lipoprotein-associated phospholipase A(2) (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p <0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo. In conclusion, AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, lipoprotein-associated phospholipase A(2), and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations. PMID:22819432

Ballantyne, Christie M; Bays, Harold E; Kastelein, John J; Stein, Evan; Isaacsohn, Jonathan L; Braeckman, Rene A; Soni, Paresh N

2012-10-01

78

Chronic changes in plasma triglyceride levels do modify platelet membrane microviscosity in rats.  

PubMed

Lipid metabolism disorders were proposed to mediate numerous cell membrane alterations in various forms of hypertension. Elevated plasma triglycerides were found to be associated with changes in membrane structure and function related to altered microviscosity in particular domains of the cell membrane. The aim of our study was to determine if an abnormal triglyceride metabolism might play a causal role in these alterations of membrane dynamics. Using genetically hypertensive rats of the Prague hereditary hypertriglyceridemic (HTG) strain we investigated whether the elevation of circulating triglycerides induced by high fructose intake and/or their lowering by chronic gemfibrozil treatment (for 10 weeks starting at the age of 6 weeks) are followed by reciprocal changes in membrane microviscosity. Two different fluorescent probes exploring either the outer membrane leaflet (TMA-DPH anisotropy) or the membrane lipid core (DPH anisotropy) were used in platelets of HTG rats. DPH (diphenylhexatriene) fluorescence anisotropy was decreased in platelets of fructose-treated HTG animals with highly elevated plasma triglyceride levels, whereas it was increased in gemfibrozil-treated HTG rats in which triglyceride levels were almost normalized. On the contrary, TMA-DPH (trimethylamino-diphenylhexatriene) anisotropy was not substantially altered in platelets from HTG rats by the above modifications of circulating triglycerides. No changes of plasma cholesterol or blood pressure were associated with the triglyceride-dependent modifications of membrane core microviscosity. Our interventional study demonstrates a major causal role of circulating triglycerides in the control of the microviscosity of membrane lipid core. PMID:10946855

Kunes, J; Devynck, M A; Zicha, J

2000-07-14

79

Measurement of triglyceride synthesis in humans using deuterium oxide and isotope ratio mass spectrometry.  

PubMed

Short-term triglyceride (TG) synthesis was measured over 48 h in four healthy males from the incorporation rate of deuterium in body water into plasma TG. Subjects drank 0.7 g D2O kg-1 estimated body water (99.8 atom% excess), followed by water containing 1.4 g D2O kg-1 water to maintain plasma deuterium enrichment at plateau. Blood samples (20 ml) were obtained before dosing and every 4 h thereafter. Subjects self-selected three meals each day. TG from each time point were separated from plasma lipids by thin-layer chromatography and combusted to water and CO2. Combustion water was vacuum distilled into Zn-containing Pyrex tubes, reduced to hydrogen gas, and analyzed for deuterium enrichment by isotope ratio mass spectrometry. Deuterium enrichment of TG increased over the 48 h study period for all four subjects studied. Superimposed on this increase were short-term non-periodic fluctuations in enrichment reflecting dietary influx and intra-individual differences in TG metabolism. The TG fractional synthetic rate (FSR) was calculated using linear and mono-exponential models. Triglyceride FSR of the subjects over the first 24 h of the study was 0.0702 +/- 0.0048 day-1 (mean +/- SEM) by the linear model and 0.0728 +/- 0.0051 day-1 by the exponential model. Deuterium enrichment reached a plateau on day 2, indicative of continuing TG synthesis in a saturated body water pool. These results are consistent with the notion of meal-dependent variability in TG synthesis into a small rapid turnover plasma TG pool. PMID:1653617

Leitch, C A; Jones, P J

1991-06-01

80

Triglyceride to HDL-C Ratio and Increased Arterial Stiffness in Children, Adolescents, and Young Adults  

PubMed Central

BACKGROUND AND OBJECTIVE: Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth. METHODS: Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379). RESULTS: There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index. CONCLUSIONS: TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases.

Khoury, Philip R.; McCoy, Connie E.; Dolan, Lawrence M.; Daniels, Stephen R.; Kimball, Thomas R.

2013-01-01

81

Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues  

PubMed Central

Chronic intermittent hypoxia (CIH) inhibits plasma lipoprotein clearance and adipose lipoprotein lipase (LPL) activity in association with upregulation of an LPL inhibitor angiopoietin-like protein 4 (Angptl4). We hypothesize that CIH inhibits triglyceride (TG) uptake via Angptl4 and that an anti-Angptl4-neutralizing antibody would abolish the effects of CIH. Male C57BL/6J mice were exposed to four weeks of CIH or intermittent air (IA) while treated with Ab (30 mg/kg ip once a week). TG clearance was assessed by [H3]triolein administration retroorbitally. CIH delayed TG clearance and suppressed TG uptake and LPL activity in all white adipose tissue depots, brown adipose tissue, and lungs, whereas heart, liver, and spleen were not affected. CD146+ CD11b? pulmonary microvascular endothelial cells were responsible for TG uptake in the lungs and its inhibition by CIH. Antibody to Angptl4 decreased plasma TG levels and increased TG clearance and uptake into adipose tissue and lungs in both control and CIH mice to a similar extent, but did not reverse the effects of CIH. The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism.

Yao, Qiaoling; Shin, Mi-Kyung; Jun, Jonathan C.; Hernandez, Karen L.; Aggarwal, Neil R.; Mock, Jason R.; Gay, Jason; Drager, Luciano F.; Polotsky, Vsevolod Y.

2013-01-01

82

Effect of chronic intermittent hypoxia on triglyceride uptake in different tissues.  

PubMed

Chronic intermittent hypoxia (CIH) inhibits plasma lipoprotein clearance and adipose lipoprotein lipase (LPL) activity in association with upregulation of an LPL inhibitor angiopoietin-like protein 4 (Angptl4). We hypothesize that CIH inhibits triglyceride (TG) uptake via Angptl4 and that an anti-Angptl4-neutralizing antibody would abolish the effects of CIH. Male C57BL/6J mice were exposed to four weeks of CIH or intermittent air (IA) while treated with Ab (30 mg/kg ip once a week). TG clearance was assessed by [H(3)]triolein administration retroorbitally. CIH delayed TG clearance and suppressed TG uptake and LPL activity in all white adipose tissue depots, brown adipose tissue, and lungs, whereas heart, liver, and spleen were not affected. CD146+ CD11b- pulmonary microvascular endothelial cells were responsible for TG uptake in the lungs and its inhibition by CIH. Antibody to Angptl4 decreased plasma TG levels and increased TG clearance and uptake into adipose tissue and lungs in both control and CIH mice to a similar extent, but did not reverse the effects of CIH. The antibody reversed the effects of CIH on LPL in adipose tissue and lungs. In conclusion, CIH inactivates LPL by upregulating Angptl4, but inhibition of TG uptake occurs predominantly via an Angptl4/LPL-independent mechanism. PMID:23386706

Yao, Qiaoling; Shin, Mi-Kyung; Jun, Jonathan C; Hernandez, Karen L; Aggarwal, Neil R; Mock, Jason R; Gay, Jason; Drager, Luciano F; Polotsky, Vsevolod Y

2013-04-01

83

JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs  

PubMed Central

Background Microsomal transfer protein inhibitors (MTPi) have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG). However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group) were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control), 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P < 0.05). Atorvastatin had the most pronounced hypolipidemic effects with a 35% reduction in LDL cholesterol and 40% reduction in TG. JTT-130 did not induce hepatic lipid accumulation compared to controls. Cholesteryl ester transfer protein (CETP) activity was reduced in a dose dependent manner by increasing doses of MTPi and guinea pigs treated with atorvastatin had the lowest CETP activity (P < 0.01). In addition the number of molecules of cholesteryl ester in LDL and LDL diameter were lower in guinea pigs treated with atorvastatin. In contrast, hepatic enzymes involved in maintaining cholesterol homeostasis were not affected by drug treatment. Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

Aggarwal, Dimple; West, Kristy L; Zern, Tosca L; Shrestha, Sudeep; Vergara-Jimenez, Marcela; Fernandez, Maria Luz

2005-01-01

84

Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-? in patients with triglyceride deposit cardiomyovasculopathy.  

PubMed

Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPAR? and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. PMID:24332944

Hirano, Ken-ichi; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Suzuki, Akira; Sakata, Yasuhiko; Sakata, Yasushi; Kobayashi, Kunihisa; Toda, Tatsushi; Fukushima, Norihide; Ishibashi-Ueda, Hatsue; Tavian, Daniela; Nagasaka, Hironori; Hui, Shu-Ping; Chiba, Hitoshi; Sawa, Yoshiki; Hori, Masatsugu

2014-01-10

85

Influence of light absorption rate by Nannochloropsis oculata on triglyceride production during nitrogen starvation.  

PubMed

This study aims to understand the role of light transfer in triglyceride fatty-acid (TG-FA) cell content and productivity from microalgae during nitrogen starvation. Large amounts of TG-FA can be produced via nitrogen starvation of microalgae in photobioreactors exposed to intense light. First, spectral absorption and scattering cross-sections of N. oculata were measured at different times during nitrogen starvation. They were used to relate the mean volumetric rate of energy absorption (MVREA) per unit mass of microalgae to the TG-FA productivity and cell content. TG-FA productivity correlated with the MVREA and reached a maximum for MVREA of 13?molh?/gs. This indicated that TG-FA synthesis was limited by the photon absorption rate in the PBR. A minimum MVREA of 13?molh?/gs was also necessary at the onset of nitrogen starvation to trigger large accumulation of TG-FA in cells. These results will be instrumental in defining protocols for TG-FA production in scaled-up photobioreactors. PMID:24835743

Kandilian, Razmig; Pruvost, Jérémy; Legrand, Jack; Pilon, Laurent

2014-07-01

86

Relationship between plasma free fatty acid, intramyocellular triglycerides and long-chain acylcarnitines in resting humans  

PubMed Central

We hypothesized that plasma non-esterified fatty acids (NEFA) are trafficked directly to intramyocellular long-chain acylcarnitines (imLCAC) rather than transiting intramyocellular triglycerides (imTG) on the way to resting muscle fatty acid oxidation. Overnight fasted adults (n= 61) received intravenous infusions of [U-13C]palmitate (0400–0830 h) and [U-13C]oleate (0800–1400 h) labelling plasma NEFA, imTG, imLCAC and im-non-esterified FA (imNEFA). Two muscle biopsies (0830 and 1400 h) were performed following 6 h, overlapping, sequential palmitate/oleate tracer infusions. Enrichment of plasma palmitate was ?15 times greater than enrichment of imTG, imNEFA-palmitate and im-palmitoyl-carnitine. Fatty acid enrichment in LCAC was correlated with imTG and imNEFA; there was a significant correlation between imTG concentrations and imLCAC concentrations in women (r= 0.51, P= 0.005), but not men (r= 0.30, P= 0.11). We estimated that ?11% of NEFA were stored in imTG. imTG NEFA storage was correlated only with NEFA concentrations (r= 0.52, P= 0.004) in women and with (r= 0.45, P= 0.02) in men. At rest, plasma NEFA are trafficked largely to imTG before they enter LCAC oxidative pools; thus, imTG are an important, central pool that regulates the delivery of fatty acids to the intracellular environment. Factors relating to plasma NEFA storage into imTG differ in men and women.

Kanaley, Jill A; Shadid, Samyah; Sheehan, Michael T; Guo, ZengKui; Jensen, Michael D

2009-01-01

87

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update.  

PubMed

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management. While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This 'residual risk' is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy. Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed. PMID:23932901

Reiner, Z

2013-09-01

88

Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia  

Microsoft Academic Search

Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The ob- jective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and

Melissa A. Austin; Karen L. Edwards; Stephanie A. Monks; Kent M. Koprowicz; John D. Brunzell; Arno G. Motulsky; Michael C. Mahaney; James E. Hixson

2003-01-01

89

Evidence for a role of tumor necrosis factor ? in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease  

Microsoft Academic Search

Elevated plasma levels of triglyceride-rich lipoproteins, a decreased high-density lipoprotein (HDL) cholesterol concentration, hyperinsulinemia, and impaired fibrinolytic function frequently aggregate in patients with premature coronary heart disease (CHD). Experimetnal studies suggest that the cytokine tumor necrosis factor ? (TNF?) produced by adipocytes plays a part in the regulation of triglyceride and glucose metabolism. The present study examined whether TNF? is

Stefan Jovinge; Anders Hamsten; Per Tornvall; Anthony Proudler; Peter Båvenholm; Carl-Göran Ericsson; Ian Godsland; Ulf de Faire; Jan Nilsson

1998-01-01

90

The Hyplip2 locus causes hypertriglyceridemia by decreased clearance of triglycerides  

Microsoft Academic Search

The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL\\/MpJ on the BALB\\/cJ back- ground. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hyper- triglyceridemia. Hypertriglyceridemia can result from in- creased intestinal or hepatic TG production and\\/or by

Corina J. A. Moen; Aart P. Tholens; Peter J. Voshol; Willeke de Haan; Louis M. Havekes; Peter Gargalovic; Aldons J. Lusis; Ko Willems van Dyk; Rune R. Frants; Marten H. Hofker; Patrick C. N. Rensen

2007-01-01

91

Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis  

Microsoft Academic Search

The relationship between apoE phenotype and plasma lipid levels was analyzed in the combined data of published studies. Accordingly, 45 population samples from 17 different countries were included in the analysis. The mean plasma values of cholesterol (CH), triglyceride (TG), and high density lipoprotein (HDL)-CH of the apoE 2\\/2, 3\\/2, 4\\/3, 4\\/4, and 4\\/2 groups were compared with the same

J. Dallongeville; S. Lussier-Cacan; J. Davignon

92

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease  

Microsoft Academic Search

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the

Carlo M. Barbagallo; Manfredi Rizzo; Davide Noto; Arian Frasheri; Vincenzo Pernice; Antonio Rubino; Daniele Pieri; Vito Pinto; Angelo B. Cefalù; Carla Giordano; Alberto Notarbartolo; Maurizio R. Averna

2006-01-01

93

HDLC and Triglyceride Levels: Relationship to Coronary Heart Disease and Treatment with Statins  

Microsoft Academic Search

The association between low-density lipoprotein cholesterol (LDL-C) levels and risk of coronary heart disease (CHD) is well established and LDL-C-lowering is currently the primary target for the treatment of dyslipidemia. However, low levels of high-density lipoprotein cholesterol (HDL-C), and high levels of triglycerides (TG) are also risk factors for CHD and modifying levels of these lipid subfractions, in addition to

Allan Gaw

2003-01-01

94

Palmitate induces insulin resistance without significant intracellular triglyceride accumulation in HepG2 cells  

Microsoft Academic Search

Previous studies showed that increased release of free fatty acids from adipocytes leads to insulin resistance and triglyceride (TG) accumulation in the liver, which may progress into hepatic steatohepatitis. We and other investigators have previously reported that palmitate induces endoplasmic reticulum stress-mediated toxicity in several tissues. This work investigated whether palmitate could induce insulin resistance and steatosis in HepG2 cells.

Jin-young Lee; Hyang-Ki Cho; Young Hye Kwon

2010-01-01

95

Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver  

PubMed Central

Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum E2 concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol 7?-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase (ACC?), malic enzyme (ME), stearoyl-CoA (?9) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ?, ? (ER? and ?) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of ER? protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

Wu, J.; Fu, W.; Huang, Y.; Ni, Y.; Zhao, R.

2013-01-01

96

Senescence-related truncation and multimerization of apolipoprotein A-I in high-density lipoprotein with an elevated level of advanced glycated end products and cholesteryl ester transfer activity.  

PubMed

To compare the change in lipoprotein metabolism with aging, we analyzed the lipid and protein compositions of individual lipoprotein fractions. Healthy and nonobese elderly participants (elderly group, n = 26) had a serum lipid profile within the normal range, although slightly higher than in young participants (control group, n = 18). However, the elderly group had a twofold higher serum uric acid level and triglyceride (TG):high-density lipoprotein cholesterol ratio. The elderly group had less antioxidant ability and elevated TG content in high-density lipoprotein (HDL) with enhanced cholesteryl ester transfer activity. An elevated level of advanced glycated end products in lipoproteins and fragmentation of apoA-I were present in the elderly group, with detected lower apoA-I level and more multimerized apoA-I in HDL. The protein levels of apoA-I, apoC-III, and serum amyloid A in lipoprotein-deficient serum were increased in the elderly group. PMID:20421239

Park, Ki-Hoon; Shin, Dong-Gu; Kim, Jae-Ryong; Cho, Kyung-Hyun

2010-06-01

97

Medium chain triglycerides and hepatic encephalopathy  

PubMed Central

The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy.

Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

1974-01-01

98

VLDL-triglyceride kinetics during hyperglycemia-hyperinsulinemia: effects of sex and obesity.  

PubMed

We have previously shown that sex and obesity independently affect basal very low density lipoprotein (VLDL)-triglyceride (TG) kinetics. In the present study, we investigated the effect of hyperglycemia-hyperinsulinemia on VLDL-TG kinetics in lean and obese men and women (n = 6 in each group). VLDL-TG kinetics were measured during basal, postabsorptive conditions and during glucose infusion (5.5 mg x kg FFM(-1) x min(-1)) by using [(2)H(5)]glycerol bolus injection in conjunction with compartmental modeling analysis. Basal VLDL-TG secretion in plasma was greater in obese than in lean men (7.8 +/- 0.6 and 2.9 +/- 0.4 micromol x l plasma(-1) x min(-1); P < 0.001) but was not different in lean and obese women (5.0 +/- 1.1 and 5.9 +/- 1.1 micromol x l plasma(-1) x min(-1)). Glucose infusion decreased the VLDL-TG secretion rate by approximately 50% in lean and obese men and in lean women (to 1.5 +/- 0.4, 4.0 +/- 0.6, and 2.2 +/- 0.4 micromol x l plasma(-1) x min(-1), respectively; all P < 0.05) but had no effect on the VLDL-TG secretion rate in obese women (4.9 +/- 1.0 micromol x l plasma(-1) x min(-1)). These results demonstrate that both sex and adiposity affect the regulation of VLDL-TG metabolism. Glucose and insulin decrease VLDL-TG production in both lean men and lean women; obesity is associated with resistance to the glucose- and insulin-mediated suppression of VLDL-TG secretion in women, but not in men. PMID:12475756

Mittendorfer, Bettina; Patterson, Bruce W; Klein, Samuel; Sidossis, Labros S

2003-04-01

99

Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations.  

PubMed

This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or 60% of total calories as carbohydrate (CHO). The protein content of the two diets was similar (15% of calories), and the fat content varied inversely with the amount of CHO (45% or 25%). The diets were consumed in random order, and measurements were made of plasma glucose, insulin, FFA, and TG concentrations at the end of each dietary period, fasting, and at hourly intervals following breakfast and lunch. The results indicated that the 60% CHO diet resulted in higher fasting plasma TG concentrations associated with higher day-long plasma insulin and TG concentrations, and lower FFA concentrations. These results do not support the view that hypertriglyceridemia is secondary to a failure of insulin to inhibit hepatic TG secretion. PMID:10999790

McLaughlin, T; Abbasi, F; Lamendola, C; Yeni-Komshian, H; Reaven, G

2000-09-01

100

Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph.  

PubMed

Abstract Apolipoprotein C-III (apoC-III) is not only predominantly synthesized by the liver but also by the small intestine. Because apoC-III is secreted from the intestine on the chylomicron along with lipid absorption, we questioned whether apoC-III might play a role in intestinal lipid absorption and/or transport. Using both wild-type (WT) and apoC-III transgenic (apoC-III Tg) mice, we showed that apoC-III Tg mice have decreased lymphatic lipid transport compared with WT mice in response to an intraduodenal infusion of radiolabeled lipid. This is associated with accumulation of radiolabeled lipids in the luminal compartment of the apoC-III Tg mice, indicating delayed lipid uptake from the lumen. The total amount of radioactive lipids in the mucosal compartment did not differ between apoC-III Tg and WT mice, but the lipid distribution analysis indicated a predominance of free fatty acids and monoacylglycerol in the mucosa of apoC-III Tg mice, implying impaired esterification capacity. Thus, the mechanisms underlying the reduced lymphatic lipid transport in apoC-III Tg mice involve both a delayed lipid uptake into enterocytes, as well as impaired esterification to form triglyceride in the mucosa. These data document a novel role for apoC-III in the uptake, re-esterification, and lymphatic transport of dietary lipids in the intestine. PMID:24760506

Wang, Fei; Kohan, Alison B; Dong, H Henry; Yang, Qing; Xu, Min; Huesman, Sarah; Lou, Danwen; Hui, David Y; Tso, Patrick

2014-01-01

101

Tocotrienol attenuates triglyceride accumulation in HepG2 cells and F344 rats.  

PubMed

Tocotrienol (T3) is an important phytonutrient found in rice bran and palm oil. T3 has gained much interest for lipid lowering effects, especially for cholesterol (Cho) by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Also, usefulness of T3 in improving triglyceride (TG) profiles has been suggested, but its efficacy and mechanism have been unclear. We investigated how T3 decreases TG concentration in cultured cells and animals. In a cell culture study, human hepatoma cells (HepG2) were incubated in a control or a fat (1 mM oleic acid)-loaded medium containing ?-T3 for 24 h. We found that 10-15 ?M ?-T3 inhibited cellular TG accumulation significantly, especially in the fat-loaded medium. This manifestation was supported by mRNA and protein expressions of fatty acid synthase, carnitine palmitoyltransferase 1, and cytochrome P450 3A4. In concordance with these results, rice bran T3 supplementation to F344 rats (5 or 10 mg T3/day/rat) receiving a high fat diet for 3 weeks significantly reduced TG and the oxidative stress marker (phospholipid hydroperoxides, PLOOH) in the liver and blood plasma. T3 supplementation did not show changes in the Cho level. These results provided new information and the mechanism of the TG-lowering effect of T3. The lipid lowering effects of dietary T3 might be mediated by the reduction of TG synthesis. PMID:22367056

Burdeos, Gregor Carpentero; Nakagawa, Kiyotaka; Kimura, Fumiko; Miyazawa, Teruo

2012-05-01

102

Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)  

SciTech Connect

The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from (14C)acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells.

Judge, S.M.; Chatterton, R.T. Jr.

1983-09-01

103

Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation.  

PubMed

Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption. PMID:23886516

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-10-01

104

Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph  

PubMed Central

Abstract Apolipoprotein C?III (apoC?III) is not only predominantly synthesized by the liver but also by the small intestine. Because apoC?III is secreted from the intestine on the chylomicron along with lipid absorption, we questioned whether apoC?III might play a role in intestinal lipid absorption and/or transport. Using both wild?type (WT) and apoC?III transgenic (apoC?III Tg) mice, we showed that apoC?III Tg mice have decreased lymphatic lipid transport compared with WT mice in response to an intraduodenal infusion of radiolabeled lipid. This is associated with accumulation of radiolabeled lipids in the luminal compartment of the apoC?III Tg mice, indicating delayed lipid uptake from the lumen. The total amount of radioactive lipids in the mucosal compartment did not differ between apoC?III Tg and WT mice, but the lipid distribution analysis indicated a predominance of free fatty acids and monoacylglycerol in the mucosa of apoC?III Tg mice, implying impaired esterification capacity. Thus, the mechanisms underlying the reduced lymphatic lipid transport in apoC?III Tg mice involve both a delayed lipid uptake into enterocytes, as well as impaired esterification to form triglyceride in the mucosa. These data document a novel role for apoC?III in the uptake, re?esterification, and lymphatic transport of dietary lipids in the intestine.

Wang, Fei; Kohan, Alison B.; Dong, H. Henry; Yang, Qing; Xu, Min; Huesman, Sarah; Lou, Danwen; Hui, David Y.; Tso, Patrick

2014-01-01

105

Dog Age and Breeds Associated with High Plasma Cholesterol and Triglyceride Concentrations  

PubMed Central

ABSTRACT The objectives of this study were to set specific dog breed and sex standards for total cholesterol (T-Cho) and total triglyceride (T-TG) concentrations in dogs and to quantify the associations between dog age and concentrations of both lipids for different breeds. Increased age was associated with higher T-Cho and T-TG concentrations in all five breed groups (P<0.05); T-Cho concentrations increased by 62.5 mg/dl between 9 and 16 years of age, and T-TG concentrations increased by 4.8 mg/dl per year of age (P<0.05). Miniature Schnauzers had the highest T-Cho concentrations of the studied breeds, while Miniature Dachshunds had the lowest concentrations (P<0.05). Veterinarians should consider dog age and breed when they use the lipid concentrations for diagnostic purposes.

USUI, Shiho; MIZOGUCHI, Yasushi; YASUDA, Hidemi; ARAI, Nobuaki; KOKETSU, Yuzo

2013-01-01

106

Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying  

PubMed Central

Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor (DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1 (intestine-Dgat1?/?) markedly reduced postprandial plasma TG and retinyl ester excursions by inhibiting chylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiency of retinol esterification, but it did reduce TG and retinoid accumulation in the small intestine. In contrast, inhibition of microsomal triglyceride transfer protein (MTP) reduced chylomicron secretion after oral fat/retinol loads, but with accumulation of dietary TG and retinoids in the small intestine. Lack of intestinal accumulation of TG and retinoids in DGAT1i-treated or intestine-Dgat1?/? mice resulted, in part, from delayed gastric emptying associated with increased plasma levels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomach through duodenal oil injection nor inhibiting the receptor for GLP-1 normalized postprandial TG or retinyl esters excursions in the absence of DGAT1 activity. In summary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptying and inhibited chylomicron secretion; however, the latter occurred when gastric emptying was normal or when lipid was administered directly into the small intestine. Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition.

Ables, Gene P.; Yang, Kryscilla Jian Zhang; Vogel, Silke; Hernandez-Ono, Antonio; Yu, Shuiqing; Yuen, Jason J.; Birtles, Susan; Buckett, Linda K.; Turnbull, Andrew V.; Goldberg, Ira J.; Blaner, William S.; Huang, Li-Shin; Ginsberg, Henry N.

2012-01-01

107

The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment  

PubMed Central

Metabolic response to the triglyceride (TG)-lowering drug, fenofibrate, is shaped by interactions between genetic and environmental factors, yet knowledge regarding the genetic determinants of this response is primarily limited to single-gene effects. Since very low-density lipoprotein (VLDL) is the central carrier of fasting TG, identifying factors that affect both total TG and VLDL–TG response to fenofibrate is critical for predicting individual fenofibrate response. As part of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, 688 individuals from 161 families were genotyped for 91 single-nucleotide polymorphisms (SNPs) in 25 genes known to be involved in lipoprotein metabolism. Using generalized estimating equations to control for family structure, we performed linear modeling to investigate whether single SNPs, single covariates, SNP–SNP interactions, and/or SNP–covariate interactions had a significant association with the change in total fasting TG and fasting VLDL–TG after 3 weeks of fenofibrate treatment. A 10-iteration fourfold cross-validation procedure was used to validate significant associations and quantify their predictive abilities. More than one-third of the significant, cross-validated SNP–SNP interactions predicting each outcome involved just five SNPs, showing that these SNPs are of key importance to fenofibrate response. Multiple variable models constructed using the top-ranked SNP–covariate interactions explained 11.9% more variation in the change in TG and 7.8% more variation in the change in VLDL than baseline TG alone. These results yield insight into the complex biology of fenofibrate response, which can be used to target fenofibrate therapy to individuals who are most likely to benefit from the drug.

Smith, Jennifer A; Arnett, Donna K; Kelly, Reagan J; Ordovas, Jose M; Sun, Yan V; Hopkins, Paul N; Hixson, James E; Straka, Robert J; Peacock, James M; Kardia, Sharon LR

2008-01-01

108

Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men.  

PubMed

Postprandial triglyceride-rich lipoproteins (TRLs) are recognized as atherogenic particles whose lipid composition and function can be modified by the composition of dietary oils. This study was designed to test the hypothesis that minor components of pomace olive oil (POMACE) can not only change the composition of postprandial TRL but also affect the clearance of triglyceride (TG) molecular species of postprandial TRL. Meals enriched in either POMACE or refined olive oil (OLIVE) were administered to 10 healthy young men. TRL were isolated from serum at 2, 4, and 6 hours postprandially, and their fatty acid and TG molecular species compositions were analyzed by gas chromatography. The apolipoprotein B concentration was determined by immunoturbidimetry. POMACE and OLIVE, differing mainly in their unsaponifiable fraction, led to similar fatty acid and TG molecular species profiles in postprandial TRL. However, POMACE-TRL presented a higher particle size, estimated as TG to apolipoprotein B ratio, which was also found for the main TG molecular species (trioleoyl-glycerol, palmitoyl-dioleoyl-glycerol, palmitoyl-oeloyl-linoleoyl-glycerol, and dioleoyl-linoleoyl-glycerol). TG from POMACE-TRL also showed higher clearance rates. In this regard, apolar TG (with a higher equivalent carbon number) disappeared more rapidly from TRL particles obtained after the ingestion of either POMACE or OLIVE. In conclusion, minor components of POMACE facilitated TG clearance from TRL by modifying their particle size and the hydrolysis of the most apolar species. PMID:24418245

Cabello-Moruno, Rosana; Martinez-Force, Enrique; Montero, Emilio; Perona, Javier S

2014-01-01

109

Reduced Triglyceride Secretion in Response to an Acute Dietary Fat Challenge in Obese Compared to Lean Mice  

PubMed Central

Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6?h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice.

Uchida, Aki; Whitsitt, Mary C.; Eustaquio, Trisha; Slipchenko, Mikhail N.; Leary, James F.; Cheng, Ji-Xin; Buhman, Kimberly K.

2012-01-01

110

Effect of Acute Negative and Positive Energy Balance on Basal Very-Low Density Lipoprotein Triglyceride Metabolism in Women  

PubMed Central

Background Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known. Objective The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women. Design Ten healthy women (age: 22.0±2.9 years, BMI: 21.2±1.3 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition. Results Fasting plasma VLDL-TG concentrations decreased by ?26% after hypocaloric feeding relative to the control trial (P?=?0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P?=?0.023) and increased VLDL-TG plasma clearance rate (by ?12%, P?=?0.016). Hypercaloric feeding increased plasma glucose concentration (P?=?0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial. Conclusion Acute dietary energy deficit (?3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (?3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women.

Bellou, Elena; Maraki, Maria; Magkos, Faidon; Botonaki, Helena; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Sidossis, Labros S.

2013-01-01

111

Independent Effects of Testosterone on Lipid Oxidation and VLDL-TG Production  

PubMed Central

Low testosterone (T) levels in men have been shown to predict development of the metabolic syndrome, but the effects of T on lipid metabolism are incompletely understood. In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy, young males received gonadotropin-releasing hormone agonist treatment 1 month prior to 3 of 4 trial days to induce castrate levels of T. On trial days, T gel was applied to the body containing either high or low physiological T dose or placebo. On the 4th trial day, participants constituted their own eugonadal controls. Each study comprised a 5-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. Short-term hypogonadism did not affect VLDL triglyceride (TG) secretion, nor did it affect VLDL-TG concentrations. It was, however, characterized by lower total lipid oxidation. In addition, acute rescue with high physiological T increased VLDL-TG secretion during both basal and clamp conditions. These data show that T can act through fast nongenomic pathways in the liver. In addition, the early hypogonadal state is characterized by decreased total lipid oxidation, but whether these changes represent early hypogonadal metabolic dysfunction warrants further investigations. T is not a major determinant of resting VLDL-TG kinetics in men.

H?st, Christian; Gormsen, Lars C.; Christensen, Britt; Jessen, Niels; Hougaard, David M.; Christiansen, Jens S.; Pedersen, Steen B.; Jensen, Michael D.; Nielsen, S?ren; Gravholt, Claus H.

2013-01-01

112

PROPERTY ANALYSIS OF TRIGLYCERIDE-BASED THERMOSETS. (R829576)  

EPA Science Inventory

Triglycerides with acrylate functionality were prepared from various oils and model triglycerides. The triglyceride-acrylates were homopolymerized and copolymerized with styrene. The cross-link densities of the resulting polymer networks were predicted utilizing the F...

113

21 CFR 862.1705 - Triglyceride test system.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Triglyceride test system. 862.1705 Section...Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

2010-04-01

114

21 CFR 862.1705 - Triglyceride test system.  

Code of Federal Regulations, 2010 CFR

...2009-04-01 2009-04-01 false Triglyceride test system. 862.1705 Section...Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

2009-04-01

115

Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis  

PubMed Central

Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8?/?) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8?/? mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8?/? mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.

Wang, Yan; Quagliarini, Fabiana; Gusarova, Viktoria; Gromada, Jesper; Valenzuela, David M.; Cohen, Jonathan C.; Hobbs, Helen H.

2013-01-01

116

Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.  

PubMed

Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(-/-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis. PMID:24043787

Wang, Yan; Quagliarini, Fabiana; Gusarova, Viktoria; Gromada, Jesper; Valenzuela, David M; Cohen, Jonathan C; Hobbs, Helen H

2013-10-01

117

[Triglycerides/HDL-cholesterol ratio: in adolescents without cardiovascular risk factors].  

PubMed

Triglycerides/HDL-cholesterol ratio (TG/HDL) is an easy resource determination and it has good correlation with the HOMA index in adults. Due to physiological insulin resistance (IR) in adolescence it is necessary to find markers of IR independent of age, sex and pubertal stage. The objective was to identify reference values of TG/HDL ratio in a population of adolescents without cardiovascular risk factors. We evaluated 943 adolescents, 429 females and 514 males between 11 and 14. Anthropometric measures were determined and body mass index was calculated (BMI). Blood was extracted after 12 hours of fasting to determine glucose, triglycerides, HDL. The metabolic syndrome (MS) was diagnosed according to criteria of NCEP/ATP III modified by Cook. We excluded adolescents with MS or any component of it. We evaluated 562 adolescents (289 women and 273 men) with a weight of 48.91 +/- 6.51kg, BMI: 18.95 +/- 1.78, systolic blood pressure of 108.12 +/- 13.60 mmHg, diastolic blood pressure: 63.82 +/- 9.43 and waist circumference: 65.09 +/- 4.54 cm. TG/HDL ratio was 1.25 +/- 0.43, with a 95 percentile of 2.05. In adults, TG/HDL ratio greater than 3 is a marker of insulin resistance. We believe that a higher value to 2.05 might be a good index of insulin resistance in adolescence. TG/HDL ratio has the advantage of being methodologically simpler, more economical and independent of pubertal stage. PMID:23610904

Soutelo, Jimena; Graffigna, Mabel; Honfi, Margarita; Migliano, Marta; Aranguren, Marcela; Proietti, Adrian; Musso, Carla; Berg, Gabriela

2012-06-01

118

Acute effects of exercise and calorie restriction on triglyceride metabolism in women  

PubMed Central

The mechanisms by which exercise reduces fasting plasma triglyceride (TG) concentrations in women and the effect of negative energy balance independent of muscular contraction are not known. Purpose The aim of this study was to evaluate the effects of equivalent energy deficits induced by exercise or calorie restriction on basal very low-density lipoprotein (VLDL) TG metabolism in women. Methods Eleven healthy women (age: 23.5±2.7 years, BMI: 21.6±1.4 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) a single exercise bout (brisk walking at 60% of peak oxygen consumption for 123±18 min, with a net energy expenditure of 2.06±0.39 MJ (~500 kcal)), ii) dietary energy restriction of 2.10±0.41 MJ, and iii) a control day of isocaloric feeding and rest (zero energy balance). Results Fasting plasma VLDL-TG concentration was ~30% lower after the exercise trial compared to the control trial (P<0.001), whereas no significant change was detected after the calorie restriction trial (P=0.297 vs control). Relative to the control condition, exercise increased the plasma clearance rate of VLDL-TG by 22% (P=0.001) and reduced hepatic VLDL-TG secretion rate by ~17% (P=0.042), whereas hypocaloric diet had no effect on VLDL-TG kinetics (P>0.2). Conclusion (i) Exercise-induced hypotriglyceridemia in women manifests through a different mechanism (increased clearance and decreased secretion of VLDL-TG) than that previously described in men (increased clearance of VLDL-TG only), and (ii) exercise affects TG homeostasis by eliciting changes in VLDL-TG kinetics that cannot be reproduced by an equivalent diet-induced energy deficit, indicating that these changes are independent of the exercise-induced negative energy balance but instead are specific to muscular contraction.

Bellou, Elena; Siopi, Aikaterina; Galani, Maria; Maraki, Maria; Tsekouras, Yiannis E.; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Magkos, Faidon; Sidossis, Labros S.

2013-01-01

119

Rheology of vegetable oil analogs and triglycerides  

Microsoft Academic Search

The rheological properties of two complex mixtures of short-chain triglycerides were experimentally determined. Dynamic or\\u000a absolute viscosities of the mixtures were measured for shear rates of 0.32 to 64.69 s?1 at temperatures between 25 and 80C. The compositions of the mixtures were based on the oil of the plant species Cuphea viscosissima VS-320, a natural source of short-chain triglycerides. The

Daniel P. Geller; John W. Goodrum

2000-01-01

120

Quantitative gas-liquid chromatography of triglycerides  

Microsoft Academic Search

To determine optimum operating conditions, an extensive study was made of the variables affecting quantitative recovery and\\u000a resolution of model triglyceride mixtures. Parameters investigated included: flash heater temperature, carrier gas flow rate,\\u000a type of carrier gas, column length, glass and metal columns, temperature program rate, linearity of detector response, physical\\u000a design of gas chromatograph, and molecular species of triglyceride.\\u000a \\u000a Results

Carter Litchfield; R. D. Harlow; Raymond Reiser

1965-01-01

121

Effects of acute exercise on postprandial triglyceride response after a high fat meal in overweight black and white adolescents  

PubMed Central

Objective We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high fat meal in overweight black vs. white adolescents. Design and Subjects Twenty-one black and 17 white adolescents (12-18 yrs, BMI >85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60 min exercise (50% VO2peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 hrs postprandially. Results There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG-area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs. control trial. Including Tanner stage, gender, total fat (kg) and VAT as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC explaining 56% and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC independent of trial. Conclusion A single bout of aerobic exercise preceding a high fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity.

Lee, SoJung; Burns, Stephen F.; White, David; Kuk, Jennifer L.; Arslanian, Silva

2014-01-01

122

Relationships among Blood Pressure, Triglycerides and Verbal Learning in African Americans  

PubMed Central

Background Individuals at greater risk for cardiovascular disease (CVD) display poorer cognitive functioning across various cognitive domains. This finding is particularly prevalent among older adults; however, few studies examine these relationships among younger adults or among African Americans. Purpose The objective was to examine the relationships among 2 cardiovascular risk factors, elevated blood pressure and elevated triglycerides, and verbal learning in a community-based sample of African Americans. Methods Measurements of blood pressure and triglycerides were obtained in 121 African-American adults and compared to performance on 3 domains of the California Verbal Learning Test-II (CVLT-II). Results Blood pressure was not related to CVLT-II performance. Triglyceride levels were inversely related to CVLT-II performance. Higher triglyceride levels were associated with poorer immediate, short delay and long delay recall. Conclusions Consistent with studies involving older participants, the current investigation shows that in a nonelderly sample of African Americans, triglyceride levels may be related to cognitive functioning. Because early detection and intervention of vascular-related cognitive impairment may have a salutary effect, future studies should include younger adults to highlight the impact of cardiovascular risk on cognition.

Sims, Regina C.; Madhere, Serge; Gordon, Shalanda; Clark, Elijah; Abayomi, Kobi A.; Callender, Clive O.; Campbell, Alfonso L.

2013-01-01

123

Novel unbiased equations to calculate triglyceride-rich lipoprotein cholesterol from routine non-fasting lipids  

PubMed Central

Background Non-fasting triglyceride-rich lipoproteins cholesterol (TRL-C) contributes to cardiovascular risk, in that it includes remnant cholesterol (RC). TRL-C is computed as total C - [LDL-C?+?HDL-C]. Such calculation applies only if LDL-C is directly measured, or obtained from a non-Friedewald’s formula, a method as yet never benchmarked against independent markers of TRL burden. Methods The Discriminant Ratio (DR) methodology was used in 120 type 2 diabetic patients in order: (i) to compute TRL-C from non-fasting lipids; (ii) to establish the performance of TRL-C and TRL-C/apoA-I (vs. TG-based markers) to grade TRLs and atherogenic dyslipidemia (AD); and (iii) to relate TRL-C with non-fasting TG. Results Depending on apoB100 availability, TRL-C (mg/dL) can be derived from non-fasting lipids in two ways: (a) total cholesterol (TC) - [(0.0106 * TC - 0.0036 * TG?+?0.017 * apoB100 - 0.27) * 38.6] - HDL-C; and (b) TC - [(0.0106 * TC - 0.0036 * TG?+?0.017 * [0.65 * (TC - HDL-C)?+?6.3] - 0.27) * 38.6] - HDL-C. Discrimination between log[TG] and TRL-C was similar (DR 0.94 and 0.84, respectively), whereas that of log[TG]/HDL-C was better than TRL-C/apoA-I (DR 1.01 vs. 0.65; p 0.0482). All Pearson’s correlations between pairs reached unity, allowing formulation of two unbiased equivalence equations: (a) TRL-C?=?97.8 * log[TG] - 181.9; and (b) TRL-C/apoA-I?=?8.15 * (log[TG]/HDL-C) - 0.18. Conclusions TRL-C and log[TG] are as effective and interchangeable for assessing remnant atherogenic particles. For grading TRL-AD, it is best to use log[TG]/HDL-C, inherently superior to TRL-C/apoA-I, while measuring the same underlying variable.

2014-01-01

124

OSBPL10 , a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism  

Microsoft Academic Search

Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N?=?426) or familial combined hyperlipidemia (N?=?684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this\\u000a initial finding, we carried out association analysis in a metabolic

Julia Perttilä; Krista Merikanto; Jussi Naukkarinen; Ida Surakka; Nicolas W. Martin; Kimmo Tanhuanpää; Vinciane Grimard; Marja-Riitta Taskinen; Christoph Thiele; Veikko Salomaa; Antti Jula; Markus Perola; Ismo Virtanen; Leena Peltonen; Vesa M. Olkkonen

2009-01-01

125

Leptin and insulin down-regulate angiopoietin-like protein 3, a plasma triglyceride-increasing factor  

Microsoft Academic Search

We reported previously that angiopoietin-like protein3 (ANGPTL3), a liver-specific secretory factor, increased plasma triglyceride (TG) via inhibition of lipoprotein lipase and free fatty acid (FFA) by activating adipose-lipolysis. The current study examined the regulation of Angptl3 by leptin and insulin, both of which are key players in the metabolic syndrome. Angptl3 expression and plasma ANGPTL3 levels were increased in leptin-resistant

Mitsuru Shimamura; Morihiro Matsuda; Yosuke Ando; Ryuta Koishi; Hiroaki Yasumo; Hidehiko Furukawa; Iichiro Shimomura

2004-01-01

126

Leptospirosis is Associated with Markedly Increased Triglycerides and Small Dense Low-Density Lipoprotein and Decreased High-Density Lipoprotein  

Microsoft Academic Search

The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol\\u000a (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-?, B, E, C-II, C-III and\\u000a lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and

Irene F. Gazi; Fotini A. Apostolou; Evangelos N. Liberopoulos; Theodosios D. Filippatos; Constantinos C. Tellis; Moses S. Elisaf; Alexandros D. Tselepis

127

High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk.  

PubMed

In this study we compared the effects of variations in dietary fat and carbohydrate (CHO) content on concentrations of triglyceride-rich lipoproteins in 8, healthy, nondiabetic volunteers. The diets contained, as a percentage of total calories, either 60% CHO, 25% fat, and 15% protein, or 40% CHO, 45% fat, and 15% protein. They were consumed in random order for 2 weeks, with a 2-week washout period in between. Measurements were obtained at the end of each dietary period of plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, remnant lipoprotein (RLP) cholesterol, and RLP triglyceride concentrations, both after an overnight fast and throughout an 8-hour period (8 A.M. to 4 P.M.) in response to breakfast and lunch. The 60% CHO diet resulted in higher (mean +/- SEM) fasting plasma triglycerides (206 +/- 50 vs 113 +/- 19 mg/dl, p = 0.03), RLP cholesterol (15 +/- 6 vs 6 +/- 1 mg/dl, p = 0.005), RLP triglyceride (56 +/- 25 vs 16 +/- 3 mg/dl, p = 0.003), and lower HDL cholesterol (39 +/- 3 vs 44 +/- 3 mg/dl, p = 0.003) concentrations, without any change in LDL cholesterol concentration. Furthermore, the changes in plasma triglyceride, RLP cholesterol, and RLP triglyceride persisted throughout the day in response to breakfast and lunch. These results indicate that the effects of lowfat diets on lipoprotein metabolism are not limited to higher fasting plasma triglyceride and lower HDL cholesterol concentrations, but also include a persistent elevation in RLPs. Given the atherogenic potential of these changes in lipoprotein metabolism, it seems appropriate to question the wisdom of recommending that all Americans should replace dietary saturated fat with CHO. PMID:11078235

Abbasi, F; McLaughlin, T; Lamendola, C; Kim, H S; Tanaka, A; Wang, T; Nakajima, K; Reaven, G M

2000-01-01

128

Physiological difference between free and triglyceride-type conjugated linoleic acid on the immune function of C57BL/6N mice.  

PubMed

Previous studies have shown the physiological significance of dietary conjugated linoleic acid (CLA) in various experimental animals and in human beings. One of the important problems to better elucidate is the difference between triglyceride (TG) and free (FFA) dietary CLA. Here, using splenocytes, this study assesses how TG- and FFA-CLA modulate immunoglobulin and various cytokine productions. In this study, C57BL/6N mice were fed an experimental diet containing 0% CLA, 0.1 or 1% FFA-CLA, or 0.1 or 1% TG-CLA for 3 weeks. The production of immunoglobulin tended to be up-regulated by 1% FFA-CLA. As a result of protein array analysis using the supernatant from splenocytes cultured with no CLA, 1% FFA-CLA, and TG-CLA, some cytokine production was shown to be remarkably regulated by dietary FFA- and TG-CLA. A total of 32 cytokines were examined, and 11-14 produced cytokines that were 2-fold up-regulated as compared with control for FFA- or TG-CLA, respectively. Especially, the production of IL-9 and MCP-5 and other cytokines was remarkably up-regulated by both FFA- and TG-CLA. In addition, seven cytokines were 2-fold down-regulated by TG-CLA. These data show that there is a slight but significant difference between the functionalities of FFA- and TG-CLA. PMID:15161243

Yamasaki, Masao; Kitagawa, Takae; Chujo, Hitomi; Koyanagi, Nami; Nishida, Eri; Nakaya, Mako; Yoshimi, Kazuma; Maeda, Hidenori; Nou, Shinsuke; Iwata, Toshio; Ogita, Kanehide; Tachibana, Hirofumi; Yamada, Koji

2004-06-01

129

Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry.  

PubMed

The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population. PMID:16958054

Bernstein, J L; Teraoka, S; Southey, M C; Jenkins, M A; Andrulis, I L; Knight, J A; John, E M; Lapinski, R; Wolitzer, A L; Whittemore, A S; West, D; Seminara, D; Olson, E R; Spurdle, A B; Chenevix-Trench, G; Giles, G G; Hopper, J L; Concannon, P

2006-11-01

130

Triglyceride-Based Screening Tests Fail to Recognize Cardiometabolic Disease in African Immigrant and African-American Men  

PubMed Central

Abstract Background The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ?150?mg/dL) and cardiometabolic disease in African and African-American men. Research Design and Methods This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35±9 years, mean±standard deviation (SD), body mass index (BMI) 28.5±5.2?kg/m2] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (SI), respectively. Cardiometabolic disease was defined by four possible subtypes—prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. Results TG levels were higher in men with cardiometabolic disease than without (88±43 versus 61±26?mg/dL, P<0.01). However, <10% of men with cardiometabolic disease had TG ?150?mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ?150?mg/dL was <10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were ?100?mg/dL (mean 71±24, range 45–100?mg/dL). Conclusions Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost.

Yu, Sophia S.K.; Ramsey, Natalie L.M.; Castillo, Darleen C.; Ricks, Madia

2013-01-01

131

Intramyocardial triglyceride quantification by magnetic resonance spectroscopy: in vivo and ex vivo correlation in human subjects  

PubMed Central

Accumulation of triglycerides (TG) in heart tissue has been associated with changes in left ventricular function. Proton magnetic resonance spectroscopy (1H-MRS) is currently the only non-invasive in vivo method to measure myocardial TG content. The primary aim of this study was to determine if these in vivo measurements are specific to myocardial TG in human subjects. Thus, in vivo 1H-MRS measurements were conducted on orthotopic heart transplant patients (n = 8) immediately before they underwent routine biopsies and ex vivo measurements were made on the endomyocardial biopsy samples. The correlation coefficient between the two measurements was 0.97, with p < 0.005, demonstrating for the first time the specificity of the in vivo measurement in human heart. From accompanying reliability experiments, the standardized typical error for the in vivo 1H-MRS method was estimated to be 7.0%, with a 95% confidence interval from 5.5 to 9.4%. These results suggest that 1H-MRS provides a specific and reliable measurement of myocardial TG content and is suitable for routine studies.

O'Connor, Robert D.; Xu, Jian; Ewald, Gregory A.; Ackerman, Joseph J. H.; Peterson, Linda R.; Gropler, Robert J.; Bashir, Adil

2013-01-01

132

Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans.  

PubMed

The relative activity of lipoprotein lipase (LPL) in different tissues controls the partitioning of lipoprotein-derived fatty acids between sites of fat storage (adipose tissue) and oxidation (heart and skeletal muscle). Here we used a reverse genetic strategy to test the hypothesis that 4 angiopoietin-like proteins (ANGPTL3, -4, -5, and -6) play key roles in triglyceride (TG) metabolism in humans. We re-sequenced the coding regions of the genes encoding these proteins and identified multiple rare nonsynonymous (NS) sequence variations that were associated with low plasma TG levels but not with other metabolic phenotypes. Functional studies revealed that all mutant alleles of ANGPTL3 and ANGPTL4 that were associated with low plasma TG levels interfered either with the synthesis or secretion of the protein or with the ability of the ANGPTL protein to inhibit LPL. A total of 1% of the Dallas Heart Study population and 4% of those participants with a plasma TG in the lowest quartile had a rare loss-of-function mutation in ANGPTL3, ANGPTL4, or ANGPTL5. Thus, ANGPTL3, ANGPTL4, and ANGPTL5, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans. PMID:19075393

Romeo, Stefano; Yin, Wu; Kozlitina, Julia; Pennacchio, Len A; Boerwinkle, Eric; Hobbs, Helen H; Cohen, Jonathan C

2009-01-01

133

Increased muscular triglyceride content and hyperglycemia in Goto-Kakizaki rat are decreased by egg white hydrolysate.  

PubMed

Abstract We investigated the fat metabolic characteristics in non-obese and diabetic Goto-Kakizaki (GK) rat and the effects of dietary egg white hydrolysate (EWH) on glucose and fat metabolism. Wistar (W) and GK (G) rats were placed into dietary casein (WC and GC) or EWH (WE and GE) group, and fed their respective diet for six weeks. Triglyceride (TG) content and stearoyl-CoA desaturase (SCD) indices in the soleus muscle were higher in the GC group than WC group in parallel with worsening serum glucose metabolic parameters. The glucose metabolic parameters were significantly improved in the GE group. The TG accumulation and SCD indices in the soleus muscle were also significantly lower in the GE group than in the GC group. In conclusion, dietary EWH not only improved glucose metabolism but also reduced both TG accumulation and SCD indices in the soleus muscle of GK rat. PMID:24467567

Ochiai, Masaru; Kuroda, Takashi; Matsuo, Tatsuhiro

2014-06-01

134

Platelet hypoaggregability in hereditary hypertriglyceridemic rats: relation to plasma triglycerides.  

PubMed

To define better the relationships between lipid metabolism disturbances and platelet aggregation we have examined these parameters in hereditary hypertriglyceridemic and control Lewis rats. Hereditary hypertriglyceridemic rats are hypertensive and have high plasma triglycerides but not elevated plasma total cholesterol. In the present study, we have demonstrated that platelets from hereditary hypertriglyceridemic rats have lowered initial rate and maximal aggregation after stimulation with thrombin or ADP in comparison with controls. These two strains did not differ significantly in the inhibition of platelet aggregation by the thromboxane A2 receptor inhibitor, SQ 29 548. In hereditary hypertriglyceridemic rats, the thrombin response, as well as the contribution of the thromboxane A2-sensitive pathway, were positively associated with the plasma level of triglycerides. Similar trend was found in Lewis rats. However, the slopes of these relationships were reduced in hereditary hypertriglyceridemic rats. These alterations of the aggregatory responses in hereditary hypertriglyceridemic rats were independent of blood pressure and plasma cholesterol level. In conclusion, our results showed a clear-cut platelet hypoaggregability to both thrombin and ADP in hypertensive hypertriglyceridemic rats. This hypoaggregability was not due to an impaired function of the thromboxane A2 pathway but could be connected with disturbances of lipid metabolism. PMID:9526957

Kunes, J; Mazeaud, M M; Devynck, M A; Zicha, J

1997-11-15

135

High serum phosphate and triglyceride levels in smoking women and men with CVD risk and type 2 diabetes  

PubMed Central

Background Both low and high serum phosphate levels may be associated with morbidity and mortality from cardiovascular disease. As smoking increases risk for type 2 diabetes (as shown by dyslipidemia and hyperglycemia), we wanted to study whether smoking and type 2 diabetes were associated with serum phosphate and triglyceride levels independently from other CVD risk factors. Methods Upon admittance to the Vindeln Health Education Centre (VHE-centre) for a four-week comprehensive lifestyle intervention, the participants (1408 women and 1096 men) completed a questionnaire that included their smoking habits – current smoker or non-smoker. We used multiple linear regression analyses to investigate the association between smoking and other CVD risk factors with S-P and S-TG levels. Results In the non-type 2 diabetes populations, the smokers, compared to the non-smokers, had higher S-P and higher serum triglycerides (S-TG). In women, serum-TG in smokers with type 2 diabetes was higher than in smokers with non-type 2 diabetes. Non-type 2 diabetes patients exhibited an inverse relation between S-Glucose (S-Glu) and S-P and a positive association with S-TG. For men only, an association was seen between age (-) and S-Crea (-) and S-P. For women only, an association was seen between BMI (-) and S-Cholesterol (+) (S-Chol) and S-P. Conclusions Compared to non-smokers, smoking women with non-type 2 diabetes and smoking men with type 2 diabetes had a higher level of S-P and S-TG. The association between smoking and S-P and S-TG levels still existed after adjusting for age and CVD risk factors in the multiple linear regression analyses. Trial registration The study has been registered as a sub-study to the Lifestyle Intervention Trial no. ISRCTN79355192.

2014-01-01

136

Hepatic diseases related to triglyceride metabolism.  

PubMed

Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24059726

Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

2013-10-01

137

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways  

PubMed Central

Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine ?-synthase. However, the mechanism by which homocysteine promotes the development and progression of hepatic steatosis is unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both the unfolded protein response and the sterol regulatory element–binding proteins (SREBPs) in cultured human hepatocytes as well as vascular endothelial and aortic smooth muscle cells. Activation of the SREBPs is associated with increased expression of genes responsible for cholesterol/triglyceride biosynthesis and uptake and with intracellular accumulation of cholesterol. Homocysteine-induced gene expression was inhibited by overexpression of the ER chaperone, GRP78/BiP, thus demonstrating a direct role of ER stress in the activation of cholesterol/triglyceride biosynthesis. Consistent with these in vitro findings, cholesterol and triglycerides were significantly elevated in the livers, but not plasmas, of mice having diet-induced hyperhomocysteinemia. This effect was not due to impaired hepatic export of lipids because secretion of VLDL-triglyceride was increased in hyperhomocysteinemic mice. These findings suggest a mechanism by which homocysteine-induced ER stress causes dysregulation of the endogenous sterol response pathway, leading to increased hepatic biosynthesis and uptake of cholesterol and triglycerides. Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia.

Werstuck, Geoff H.; Lentz, Steven R.; Dayal, Sanjana; Hossain, Gazi S.; Sood, Sudesh K.; Shi, Yuan Y.; Zhou, Ji; Maeda, Nobuyo; Krisans, Skaidrite K.; Malinow, M. Rene; Austin, Richard C.

2001-01-01

138

Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth.  

PubMed

Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants. Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia. Our study of 1,742 French-Canadians aged 9, 13, and 16 years did not provide evidence of a potential predisposition to IRS related to either FABP2 or MTP genotypes. However, we observed a heterogeneity of the FABP2 effect by IRS status on total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) concentrations (P for interaction=0.045, 0.018, and 0.017, respectively). Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001). IRS did not modify the associations between the MTP polymorphism and any of the biochemical parameters. Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia. PMID:15547295

Stan, Simona; Lambert, Marie; Delvin, Edgard; Paradis, Gilles; O'loughlin, Jennifer; Hanley, James A; Levy, Emile

2005-02-01

139

Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.  

PubMed

Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

2013-07-01

140

Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice  

PubMed Central

Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

Forrest, Lolita M.; Lough, Christopher M.; Chung, Soonkyu; Boudyguina, Elena Y.; Gebre, Abraham K.; Smith, Thomas L.; Colvin, Perry L.; Parks, John S.

2013-01-01

141

Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat.  

PubMed

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein. PMID:18971352

Laplante, Mathieu; Festuccia, William T; Soucy, Geneviève; Blanchard, Pierre-Gilles; Renaud, Alexandra; Berger, Joel P; Olivecrona, Gunilla; Deshaies, Yves

2009-01-01

142

Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Patients With Very High Triglyceride Levels (from the Multicenter, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] Trial)  

Microsoft Academic Search

AMR101 is an omega-3 fatty acid agent containing ?96% eicosapentaenoic acid ethyl ester and no docosahexaenoic acid. Previous smaller studies suggested that highly purified eicosapentaenoic acid lowered triglyceride (TG) levels without increasing low-density lipoprotein (LDL) cholesterol levels. TG-lowering therapies such as fibrates, and fish oils containing both eicosapentaenoic acid and docosahexaenoic acid, can substantially increase LDL cholesterol levels when administered

Harold E. Bays; Christie M. Ballantyne; John J. Kastelein; Jonathan L. Isaacsohn; Rene A. Braeckman; Paresh N. Soni

2011-01-01

143

Inhibition of ATP citrate lyase induces triglyceride accumulation with altered fatty acid composition in cancer cells.  

PubMed

De novo lipogenesis is activated in most cancers and several lipogenic enzymes have been implicated as therapeutic targets. Here, we demonstrate a novel function of the lipogenic enzyme, ATP citrate lyase (ACLY), in lipid metabolism in cancer cells. ACLY depletion by small interfering RNAs caused growth suppression and/or apoptosis in a subset of cancer cell lines. To investigate the effect of ACLY inhibition on lipid metabolism, metabolome and transcriptome analysis was performed. ACLY depletion blocks the fatty acid chain elongation from C16 to C18 in triglyceride (TG), but not in other lipid classes. Meanwhile, wild-type ACLY overexpression enhanced fatty acid elongation of TG, whereas an inactive mutant ACLY did not change it. ACLY depletion-mediated blockade of fatty acid elongation was coincident with downregulation of long-chain fatty acid elongase ELOVL6, which resides in endoplasmic reticulum (ER). Paradoxically, ACLY depletion-mediated growth suppression was associated with TG accumulation. ACLY depletion downregulated the expression of carnitine palmitoyltransferase 1A, which is a mitochondrial fatty acid transporter. Consistent with this finding, metabolome analysis revealed that ACLY positively regulates the carnitine system, which plays as an essential cofactor for fatty acid transport across mitochondrial membrane. AICAR, an activator of mitochondrial fatty acid oxidation (FAO), significantly reduced ACLY depletion-mediated TG accumulation. These data indicate that inhibition of ACLY might affect both fatty acid elongation in ER and FAO in mitochondria, thereby explaining the TG accumulation with altered fatty acid composition. This phenotype may be a hallmark of growth suppression mediated by ACLY inhibition. PMID:24310723

Migita, Toshiro; Okabe, Sachiko; Ikeda, Kazutaka; Igarashi, Saori; Sugawara, Shoko; Tomida, Akihiro; Soga, Tomoyoshi; Taguchi, Ryo; Seimiya, Hiroyuki

2014-07-01

144

Association between periodontal disease and plasma levels of cholesterol and triglycerides  

PubMed Central

Objective: untreated periodontal disease seems to cause low grade systemic inflammation and blood lipid alteration leading to increased cardiovascular disease risk. To start testing this hypothesis in colombian patients, a multicentre study was conducted including the three main state capitals: bogota, medellin and cali. Methods: in this study 192 (28.4%) advanced and 256 (37.8%) moderate periodontitis patients were investigated for socio-demographic variables, city of precedence, periodontal parameters, smoking, red complex periodontopathic bacteria, serum antibodies against porphyromonas gingivalis and aggregatibacter actinomycetemcomitans and blood lipids including total cholesterol, hdl, ldl and triglycerides (tg). Those parameters were compared to 229 (33.8%) controls having periodontal health or gingivitis. Results: advanced periodontitis had worst periodontal indexes, than moderate periodontitis and controls. Interestingly, higher hdl and tg levels were present in periodontitis. Bmi <30 and smoking were associated with increased hdl, hdl-35, ldl and tg, while glycemia >100 mg/dl associated with hdl, hdl-35 and tg. Tannerella forsythia showed a significant association with hdl-35 in bivariate analysis and serum igg1 against p. Gingivalis associated with hdl-35 and serum igg1 against t. Forsythia associated with tg and serum igg2 against a. Actinomycetemcomitans correlated with levels of hdl y hdl-35. In logistic regression the periodontitis patients from cali presented reduced hdl levels as compared to bogota and medellin patients. Presence of igg1 antibodies against p. Gingivalis and a. Actinomycetemcomitans correlated with reduced hdl levels. Conclusion: this study confirmed that untreated periodontitis generates alteration in serum lipid levels and systemic bacterial exposure against important periodontopathic bacteria could be the biological link.

Lafaurie, Gloria Ines; Millan, Lina Viviana; Ardila, Carlos Martin; Duque, Andres; Novoa, Camilo; Lopez, Diego; Contreras, Adolfo

2013-01-01

145

Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin.  

PubMed

Administration of a single nonlethal dose (20 micrograms/kg) of 2,3,7,8-tetrachlorodibenzo-p-dioxin to New Zealand male rabbits, both on a standard and on a cholesterol (0.5% in the diet) regimen, resulted in a significant increase of plasma triglyceride levels. Triglycerides were particularly raised in the very low-density lipoprotein fraction; no significant apolipoprotein changes, as assessed by an analytical isoelectrofocusing procedure, could be determined. Concomitant to the increased triglyceridemia, aortic triglycerides were also significantly elevated in 2,3,7,8-tetrachlorodibenzo-p-dioxin-pretreated rabbits, both on the standard and on the cholesterolemic regimen. These findings suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin, possibly by inhibiting triglyceride breakdown, may induce an atherogenic form of hypertriglyceridemia in a standard experimental model of atherosclerosis. PMID:6464024

Lovati, M R; Galbussera, M; Franceschini, G; Weber, G; Resi, L; Tanganelli, P; Sirtori, C R

1984-08-01

146

21 CFR 862.1705 - Triglyceride test system.  

Code of Federal Regulations, 2013 CFR

...a) Identification. A triglyceride test system is a device intended to measure triglyceride (neutral fat) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of patients with diabetes mellitus,...

2013-04-01

147

Analysis of the Triglycerides of Some Vegetable Oils.  

ERIC Educational Resources Information Center

Explains that triglycerides consist of a mixture of different compounds, depending on the total number of fatty acid constituents. Details the method and instrumentation necessary for students to analyze a vegetable oil for its triglyceride content. Describes sample results. (CW)

Farines, Marie; And Others

1988-01-01

148

Glass paper chromatography and elatography of triglycerides  

Microsoft Academic Search

A degree of reverse phase separation of triglycerides can be obtained with ascending chromatography on uncoated glass paper\\u000a using a pyridine: water solvent system. The same Rf values result when silica gel coated paper is used. To extend the usefulness of this separation, the glyceryl esters are\\u000a converted to methyl esters in situ using sodium methoxide. This permits, on silica

J. R. Swartwout; R. J. Gross

1964-01-01

149

Medium chain triglycerides and structured lipids  

Microsoft Academic Search

Lipids are an essential component of our body composition and necessary in our daily food intake. Conventional fats and oils\\u000a are composed of glycerides of long chain fatty acids and are designated as long chain triglycerides (LCT). Body fat as well\\u000a as the fats and oils in our daily intake fall into this category. In enteral and parenteral hyperalimentation, we

Vigen K. Babayan

1987-01-01

150

The plasma parameter log (TG\\/HDLC) as an atherogenic index: correlation with lipoprotein particle size and esterification rate inapob-lipoprotein-depleted plasma (FER HDL)  

Microsoft Academic Search

Objectives: To evaluate if logarithm of the ratio of plasma concentration of triglycerides to HDL-cholesterol (Log[TG\\/HDL-C]) correlates with cholesterol esterification rates in apoB-lipoprotein-depleted plasma (FERHDL) and lipoprotein particle size.Design and methods: We analyzed previous data dealing with the parameters related to the FERHDL (an indirect measure of lipoprotein particle size). In a total of 1433 subjects from 35 cohorts with

Jiri Frohlich

2001-01-01

151

Static and Dynamic Wetting Behavior of Triglycerides on Solid Surfaces  

Microsoft Academic Search

Triglyceride wetting properties on solid surfaces of different hydro-phobicities were investigated using three different methods, namely, the sessile drop method for static contact angle measurements, the Wilhelmy method for dynamic contact angle measurements, and the captive bubble method to investigate thin triglyceride film stability. For solid surfaces having a surface free energy higher than the surface tension of triglycerides (tributyrin,

Marie-Caroline Michalski; Benilde J. V. Saramago

2000-01-01

152

Triglycerides in embryogenic conifer calli: a comparison with zygotic embryos  

Microsoft Academic Search

Triglycerides in developing zygotic embryos of Norway spruce and loblolly pine were found to accumulate continuously during the course of development, comprising nearly 50% of the fresh weight of a mature embryo. Embryogenic calli of these two species contained dramatically lower levels of triglycerides. Abscisic acid treatments promoted both embryo production and triglyceride accumulation in Norway spruce cultures. A method

R. P. Feirer; J. H. Conkey; S. A. Verhagen

1989-01-01

153

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study  

PubMed Central

OBJECTIVE—Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS—We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS—After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 ± 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 × 10?5). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS—Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.

Coletta, Dawn K.; Schneider, Jennifer; Hu, Shirley L.; Dyer, Thomas D.; Puppala, Sobha; Farook, Vidya S.; Arya, Rector; Lehman, Donna M.; Blangero, John; DeFronzo, Ralph A.; Duggirala, Ravindranath; Jenkinson, Christopher P.

2009-01-01

154

OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism.  

PubMed

Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N = 426) or familial combined hyperlipidemia (N = 684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this initial finding, we carried out association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing association of multiple OSBPL10 SNPs with high serum TG levels (>95th percentile). To investigate whether OSBPL10 could be the gene underlying the observed linkage and association, we carried out functional experiments in the human hepatoma cell line Huh7. Silencing of OSBPL10 increased the incorporation of [(3)H]acetate into cholesterol and both [(3)H]acetate and [(3)H]oleate into triglycerides and enhanced the accumulation of secreted apolipoprotein B100 in growth medium, suggesting that the encoded protein ORP10 suppresses hepatic lipogenesis and very-low-density lipoprotein production. ORP10 was shown to associate dynamically with microtubules, consistent with its involvement in intracellular transport or organelle positioning. The data introduces OSBPL10 as a gene whose variation may contribute to high triglyceride levels in dyslipidemic Finnish subjects and provides evidence for ORP10 as a regulator of cellular lipid metabolism. PMID:19554302

Perttilä, Julia; Merikanto, Krista; Naukkarinen, Jussi; Surakka, Ida; Martin, Nicolas W; Tanhuanpää, Kimmo; Grimard, Vinciane; Taskinen, Marja-Riitta; Thiele, Christoph; Salomaa, Veikko; Jula, Antti; Perola, Markus; Virtanen, Ismo; Peltonen, Leena; Olkkonen, Vesa M

2009-08-01

155

Free fatty acids/triglycerides increase ocular and subcutaneous blood flow.  

PubMed

Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU. kg(-1). min(-1)) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 +/- 3% (P < 0.001) and in retinal blood flow by 60 +/- 23% (P = 0.0125). PSV increased by 27 +/- 8% (P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 +/- 38% (P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 +/- 5% (P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome. PMID:11124134

Polak, K; Schmetterer, L; Luksch, A; Gruber, S; Polska, E; Peternell, V; Bayerle-Eder, M; Wolzt, M; Krebs, M; Roden, M

2001-01-01

156

Polyunsaturated fatty acids effect on serum triglycerides concentration in presence of metabolic syndrome components. The Alaska-Siberia Project  

PubMed Central

Serum fatty acids (FA) have wide effects on metabolism: Serum saturated fatty acids (SFA) increase triglyceride (TG) levels in plasma while polyunsaturated fatty acids (PUFA) reduce them. Traditionally, Eskimos have a high consumption of omega -3 fatty acids (?–3 FA), but the westernization of their food habits have increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TG in the presence of metabolic syndrome components. We included 212 men and 240 women (age 47.9±15.7 y, BMI 26.9±5.3) from four villages located in Alaska for a cross sectional study. Generalized linear models were employed to build surface responses of TG as in functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI and village. The effects of individual FAs were assessed by multiple linear regression analysis and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, p = 0.018) and BMI (r = 0.42, p<0.001). TG concentration showed negative associations with 20:3?-6 (r =? 0.16, p = 0.001), 20:4?-6 (r = ?0.14, p=0.005), 20:5?-3 (r = ?0.17, p<0.001) and 22:5?-3 (r = ?0.26, p<0.001), and positive associations with palmitic acid (r = 0.16, p<0.001) and 18:3?-3 (r = 0.15, p<0.001). The surface response analysis suggested that the effect of palmitic acid on TG is blunted in different degrees according to the PUFA chemical structure. The long chain ?-3, even in presence of high levels of SF, was associated with lower triglyceride levels. Eicosapentanoic acid (20:5?3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, while SFA was positively associated, and large chain PUFA negatively. The westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease.

Lopez-Alvarenga, Juan C.; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth; Voruganti, V. Saroja; Comuzzie, Anthony G

2009-01-01

157

A High Fat Diet and theThr54 polymorphism of FABP2 Reduces Plasma Triglyceride-Rich Lipoproteins  

PubMed Central

The Thr54 allele of the fatty acid binding protein 2 (FABP2) DNA polymorphism is associated with increased triglyceride-rich lipoproteins (TRL). We hypothesized that the TRL response to diets of varied fat content is affected by the FABP2 A54T polymorphism, specifically that a high fat diet would reduce TRL and that the T54 allele would have an enhanced response. Sixteen healthy, post-menopausal women completed a cross-over dietary intervention that included three 8-week, isocaloric diet treatments. The treatments consisted of high fat (HF, 40% of energy as fat), low fat (LF, 20% of energy), and low fat + n-3 fatty acids (LF+n-3, 20% of energy plus 3% as n-3 fatty acids). Eight subjects were homozygous for the wild-type (A/A) of the FABP2 polymorphism while eight subjects had at least one Thr54 allele (7 = A/T, 1 = T/T). HF diet showed significantly reduced plasma triglycerides (TG), chylomicron TG, and very-low density lipoprotein TG from baseline in all participants. Although, carriers of the Thr54 allele of the FABP2 polymorphism had significantly reduced TLR, there is no evidence of an interaction which does not support our hypothesis. The Ala54 allele did not influence the dietary effects on the plasma lipids.

McColley, Steven P; Georgopoulos, Angeliki; Young, Lindsay R; Kurzer, Mindy S; Redmon, J Bruce; Raatz, Susan K

2011-01-01

158

High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and\\/or high triglyceride concentrations, and its association with insulin and c-reactive protein  

Microsoft Academic Search

We tested whether low high-density lipoprotein cholesterol (HDL-C) and\\/or high triglycerides are associated to abnormal HDL subclasses distribution and composition, and their relationships with fasting insulin and C-reactive protein (CRP). Four groups of adolescents were studied: group 1 (HDL-C?35mg\\/dl+TG?150mg\\/dl; n=16); group 2 (isolated HDL-C?35mg\\/dl; n=31); group 3 (isolated TG?150mg\\/dl; n=20); and group 4 (CT<200mg\\/dl, HDL-C>35mg\\/dl, LDL-C<130mg\\/dl, and TG<150mg\\/dl; n=39). Tanner

Aida Medina-Urrutia; Juan G. Juarez-Rojas; Rocio Martínez-Alvarado; Esteban Jorge-Galarza; Rosalinda Posadas-Sánchez; Guillermo Cardoso-Saldaña; Enrique Mendoza-Perez; Carlos Posadas-Romero

2008-01-01

159

Serum factors influencing cultured hepatocyte exogenous and endogenous triglyceride.  

PubMed

Rat hepatocyte monolayer triglyceride content was increased modestly by incubations with apolipoprotein E-containing triglyceride emulsions or chylomicrons (exogenous) and was increased substantially by increasing media free fatty acid concentrations (endogenous). The secretion of both endogenous and exogenous triglyceride into media was enhanced by additions of serum and serum components. These additions not only enhanced hepatocyte triglyceride secretion but also, because of the absence of media lipolysis, more triglyceride was recovered in the system. Lipoprotein-free serum replicated the effect of whole serum. Lipoprotein produced a more modest secretory response. The apolipoprotein C components were the only ones that enhanced hepatic triglyceride secretion. Both lipoprotein-free plasma and lipoprotein enhanced the in vitro transfer of hepatocyte exogenous triglyceride to fibroblast. PMID:2372060

Levinson, M; Oswald, B; Quarfordt, S

1990-07-01

160

Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension  

PubMed Central

Background In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.

Moura, Rafaela do Socorro Souza e Silva; Vasconcelos, Daniel Franca; Freitas, Eduardo; de Moura, Flavio Jose Dutra; Rosa, Tania Torres; Veiga, Joel Paulo Russomano

2014-01-01

161

Transgenic Angiopoietin-Like (Angptl)4 Overexpression and Targeted Disruption of Angptl4 and Angptl3: Regulation of Triglyceride Metabolism  

Microsoft Academic Search

deficient mice displayed hypotriglyceridemia and increased PHP LPL activity, with greater effects in the fasted compared with the fed state. Angptl3-deficient mice also displayed hy- potriglyceridemia with elevated PHP LPL activity, but these mice showed a greater effect in the fed state. Mice deficient in both Angptl proteins showed an additive effect on plasma triglycerides and did not survive past

Anja Koster; Y. Bernice Chao; Marian Mosior; Amy Ford; Patricia A. Gonzalez-DeWhitt; John E. Hale; Deshan Li; Yubin Qiu; Christopher C. Fraser; Derek D. Yang; Josef G. Heuer; S. Richard Jaskunas; Patrick Eacho

2010-01-01

162

Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels.  

PubMed

The metabolic syndrome, a common disorder including glucose intolerance and dyslipidemia, poses a major public health issue. Patients with high blood lipids, such as triglycerides, are at high risk in developing atherosclerotic cardiovascular diseases. To identify genes involved in metabolism, we performed RNA-seq experiments on the liver and fat in mice treated with a high-fat diet or fasting, and identified Gm6484 (named Lipasin) as a novel nutritionally regulated gene. Human LIPASIN is liver specific, while the mouse one is enriched in the liver and fat, including both brown and white adipose tissues. Obesity increases liver Lipasin, whereas fasting reduces its expression in fat. ANGPTL3 (Angiopoietin-like 3) and ANGPTL4 are critical regulators of blood lipids. LIPASIN shares homology with ANGPTL3's N-terminal domain that is needed for lipid regulation, and with ANGPTL4's N-terminal segment that mediates lipoprotein lipase (LPL) binding. Lipasin overexpression by adenoviruses in mice increases serum triglyceride levels, and a recombinant Lipasin inhibits LPL activity. Therefore, a potential mechanism for Lipasin-mediated triglyceride elevation is through reduced triglyceride clearance by LPL inhibition. Lipasin is thus a novel nutritionally-regulated liver-enriched factor that plays a role in lipid metabolism. PMID:22809513

Zhang, Ren

2012-08-10

163

AdR1-TG/TALLYHO mice have improved lipid accumulation and insulin sensitivity  

PubMed Central

Background Overexpression of adiponectin receptor 1 in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. To investigate the effects of enhanced adiponectin actions in TALLYHO (TH) diabetic mouse model, we crossed the adiponectin receptor 1 macrophage-specific transgenic mice (AdR1-TG) with the TALLYHO diabetic mice (TH) to examine the changes of lipid accumulation and insulin sensitivity in these mice. Methods AdR1-TG/TH and the control WT/TH mice were fed either normal diet or high fat diet for twenty-eight weeks. Whole body weights of these mice were measured and mouse sera were analyzed for the levels of cholesterol, triglyceride, and free fatty acids. Glucose tolerance testing (GTT) and insulin tolerance testing (ITT) in these mice were performed to investigate systemic insulin sensitivity in vivo. Molecular markers for insulin signaling pathway in mouse skeletal muscle tissues, IRS-1 and AKT, were examined. Mouse serum insulin levels were measured and Sirt1 gene expression in mouse pancreatic tissues was also quantified related to the insulin secretion. The Caspase 3 protein levels were analyzed by Western blot methods. Results Compared to the control WT/TH mice, AdR1-TG/TH mice showed significantly lower body weights under either normal diet or high fat diet and the mouse serum levels of cholesterol, triglyceride and free fatty acids were significantly decreased in the transgenic crossed mice when compared to those from the control mice. Improved GTT and ITT tests indicating increased systemic insulin sensitivity in the transgenic crossed mice demonstrated the enhanced adiponectin actions on the systemic metabolism in vivo. The increases of insulin secretion and its related gene expression were also detected in the transgenic crossed mice. In contrast, the control mice showed hypertrophy pancreases companying with high apoptosis gene expression. These results suggest that enhanced adiponectin actions by overexpressing adiponectin receptor 1 in macrophages can provide unique interactions with the metabolic tissues/cells, improving lipid accumulation and insulin sensitivity in TALLYHO diabetic mice.

Luo, Nanlan; Wang, Xiangdong; Zhang, Wei; Garvey, W. Timothy; Fu, Yuchang

2013-01-01

164

Absence of Nitric Oxide Synthase 3 Increases Amyloid ?-Protein Pathology in Tg-5xFAD Mice  

PubMed Central

Aim The abnormal accumulation, assembly and deposition of the amyloid ?-protein (A?) are prominent pathological features of patients with Alzheimer’s disease (AD) and related disorders. A number of factors in the brain can influence A? accumulation and associated pathologies. The aim of the present study was to determine the consequences of deleting nitric oxide synthase (NOS) 3, the endothelial form of NOS, in Tg-5xFAD mice, a model of parenchymal AD-like amyloid pathology. Methods Tg-5xFAD mice were bred with NOS3?/? mice. Cohorts of Tg-5xFAD mice and bigenic Tg-5xFAD/NOS3?/? mice were aged to six months followed by collection of the blood and brain tissues from the mice for biochemical and pathological analyses. Results ELISA analyses show that the absence of NOS3 results in elevated levels of cerebral and plasma A? peptides in Tg-5xFAD mice. Immunohistochemical analyses show that the absence of NOS3 increased the amount of parenchymal A? deposition and fibrillar amyloid accumulation in Tg-5xFAD mice. The elevated levels of A? were not due to changes in the expression levels of transgene encoded human amyloid precursor protein (APP), endogenous ?-secretase, or increased proteolytic processing of APP. Conclusions The results from this study suggest that the loss of NOS3 activity enhances A? pathology in Tg-5xFAD mice. These findings are similar to previous studies of NOS2 deletion suggesting that reduced NOS activity and NO levels enhance amyloid-associated pathologies in human APP transgenic mice.

Hu, Zishuo Ian; Kotarba, Ann Marie E.; Van Nostrand, William E.

2013-01-01

165

Endothelial dysfunction in adipose triglyceride lipase deficiency.  

PubMed

Systemic knockout of adipose triglyceride lipase (ATGL), the pivotal enzyme of triglyceride lipolysis, results in a murine phenotype that is characterized by progredient cardiac steatosis and severe heart failure. Since cardiac and vascular dysfunction have been closely related in numerous studies we investigated endothelium-dependent and -independent vessel function of ATGL knockout mice. Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts showed that ATGL knockout mice suffer from pronounced micro- and macrovascular endothelial dysfunction. Experiments with agonists directly targeting vascular smooth muscle cells revealed the functional integrity of the smooth muscle cell layer. Loss of vascular reactivity was restored ~50% upon treatment of ATGL knockout mice with the PPAR? agonist Wy14,643, indicating that this phenomenon is partly a consequence of impaired cardiac contractility. Biochemical analysis revealed that aortic endothelial NO synthase expression and activity were significantly reduced in ATGL deficiency. Enzyme activity was fully restored in ATGL mice treated with the PPAR? agonist. Biochemical analysis of perivascular adipose tissue demonstrated that ATGL knockout mice suffer from perivascular inflammatory oxidative stress which occurs independent of cardiac dysfunction and might contribute to vascular defects. Our results reveal a hitherto unrecognized link between disturbed lipid metabolism, obesity and cardiovascular disease. PMID:24657704

Schrammel, Astrid; Mussbacher, Marion; Wölkart, Gerald; Stessel, Heike; Pail, Karoline; Winkler, Sarah; Schweiger, Martina; Haemmerle, Guenter; Al Zoughbi, Wael; Höfler, Gerald; Lametschwandtner, Alois; Zechner, Rudolf; Mayer, Bernd

2014-06-01

166

Failure simulations of triglyceride-based adhesives  

NASA Astrophysics Data System (ADS)

The use of natural plant oils in the production of adhesives has been the focus of a large amount of research because the natural oils are a renewable resource which have environmental and economic advantages over the petroleum-derived chemicals used in traditional adhesives. An off-lattice Monte Carlo simulation was used to model the formation of networks consisting of the triglycerides found in soybean, linseed and olive oils and networks made from other `theoretical' natural oils. Each of these networks has a different number of carbon-carbon double bonds n present in a given triglyceride molecule. The stress-strain behavior of these networks is studied using large-scale molecular dynamics simulations. Tensile strains are applied to the networks and it is observed that with increasing n the failure stress increases but the failure strain decreases. Also, at low values of n, the systems have large voids form while the system is strained and then the system fails cohesively. However for large n, no significant voiding is observed and the system fails close to the interface. The simulation results are shown to be consistent with vector percolation theoretical predictions for how the failure stress and the crosslink density relate to n.

Lorenz, Christian D.; Stevens, Mark J.; Wool, Richard P.

2004-03-01

167

Endothelial dysfunction in adipose triglyceride lipase deficiency  

PubMed Central

Systemic knockout of adipose triglyceride lipase (ATGL), the pivotal enzyme of triglyceride lipolysis, results in a murine phenotype that is characterized by progredient cardiac steatosis and severe heart failure. Since cardiac and vascular dysfunction have been closely related in numerous studies we investigated endothelium-dependent and -independent vessel function of ATGL knockout mice. Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts showed that ATGL knockout mice suffer from pronounced micro- and macrovascular endothelial dysfunction. Experiments with agonists directly targeting vascular smooth muscle cells revealed the functional integrity of the smooth muscle cell layer. Loss of vascular reactivity was restored ~ 50% upon treatment of ATGL knockout mice with the PPAR? agonist Wy14,643, indicating that this phenomenon is partly a consequence of impaired cardiac contractility. Biochemical analysis revealed that aortic endothelial NO synthase expression and activity were significantly reduced in ATGL deficiency. Enzyme activity was fully restored in ATGL mice treated with the PPAR? agonist. Biochemical analysis of perivascular adipose tissue demonstrated that ATGL knockout mice suffer from perivascular inflammatory oxidative stress which occurs independent of cardiac dysfunction and might contribute to vascular defects. Our results reveal a hitherto unrecognized link between disturbed lipid metabolism, obesity and cardiovascular disease.

Schrammel, Astrid; Mussbacher, Marion; Wolkart, Gerald; Stessel, Heike; Pail, Karoline; Winkler, Sarah; Schweiger, Martina; Haemmerle, Guenter; Al Zoughbi, Wael; Hofler, Gerald; Lametschwandtner, Alois; Zechner, Rudolf; Mayer, Bernd

2014-01-01

168

Dietary oxidized linoleic acid lowers triglycerides via APOA5/APOClll dependent mechanisms.  

PubMed

Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids. The decreases in plasma TG levels were accompanied by significant increases (P<0.001) in the expressions of APOA5 and acetyl-CoA oxidase genes as well as a significant (P<0.04) decrease in APOClll gene expression. Oxidized lipids have been suggested to be ligands for peroxisome proliferator-activated receptor (PPAR*). However, there were no increases in the mRNA or protein levels of PPAR* in the oxidized linoleic acid fed animals. These results suggest that oxidized fatty acids may act through an APOA5/APOClll mechanism that contributes to lowering of TG levels other than PPAR* induction. PMID:18243209

Garelnabi, Mahdi; Selvarajan, Krithika; Litvinov, Dmitry; Santanam, Nalini; Parthasarathy, Sampath

2008-08-01

169

Dietary oxidized linoleic acid lowers triglycerides via APOA5/APOClll dependent mechanisms  

PubMed Central

Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids. The decreases in plasma TG levels were accompanied by significant increases (P < 0.001) in the expressions of APOA5 and acetyl-CoA oxidase genes as well as a significant (P < 0.04) decrease in APOClll gene expression. Oxidized lipids have been suggested to be ligands for peroxisome proliferator-activated receptor (PPAR?). However, there were no increases in the mRNA or protein levels of PPAR? in the oxidized linoleic acid fed animals. These results suggest that oxidized fatty acids may act through an APOA5/APOClll mechanism that contributes to lowering of TG levels other than PPAR? induction.

Garelnabi, Mahdi; Selvarajan, Krithika; Litvinov, Dmitry; Santanam, Nalini; Parthasarathy, Sampath

2008-01-01

170

Relationship between total cholesterol\\/high-density lipoprotein cholesterol ratio, triglyceride\\/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses  

Microsoft Academic Search

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)\\/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)\\/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442

Lianqun Jia; Shiyin Long; Mingde Fu; Bingyu Yan; Ying Tian; Yanhua Xu; Lantu Gou

2006-01-01

171

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements  

Microsoft Academic Search

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation\\u000a fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol\\u000a measurements. In vivo, the intravenous infusion of LEH (5.6 mL\\/kg, n=6) elevated serum triglycerides (+92% vs. baseline, PPP<.01) and had no effect on serum HDL cholesterol. In addition, LEH did

F. Abdullah; M. Whiteford; G. Mathiak; P. Ovadia; A. Rudolph; L. F. Neville; R. Rabinovici

1997-01-01

172

Polyunsaturated fatty acids effect on serum triglycerides concentration in the presence of metabolic syndrome components. The Alaska-Siberia Project.  

PubMed

Serum fatty acids (FAs) have wide effects on metabolism: Serum saturated fatty acids (SFAs) increase triglyceride (TG) levels in plasma, whereas polyunsaturated fatty acids (PUFAs) reduce them. Traditionally, Eskimos have a high consumption of omega-3 fatty acids (omega3 FAs); but the Westernization of their food habits has increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TGs in the presence of metabolic syndrome components. We included 212 men and 240 women (age, 47.9 +/- 15.7 years; body mass index [BMI], 26.9 +/- 5.3) from 4 villages located in Alaska for a cross-sectional study. Generalized linear models were used to build surface responses of TG as functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI, and village. The effects of individual FAs were assessed by multiple linear regression analysis, and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, P = .018) and BMI (r = 0.42, P < .001). Triglyceride concentration showed negative associations with 20:3omega6 (r = -0.16, P = .001), 20:4omega6 (r = -0.14, P = .005), 20:5omega3 (r = -0.17, P < .001), and 22:5omega3 (r = -0.26, P < .001), and positive associations with palmitic acid (r = 0.16, P < .001) and 18:3omega3 (r = 0.15, P < .001). The surface response analysis suggested that the effect of palmitic acid on TG is blunted in different degrees according to the PUFA chemical structure. The long-chain omega3, even in the presence of high levels of saturated fat, was associated with lower TG levels. Eicosapentaenoic acid (20:5omega3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, whereas SFA was positively associated and large-chain PUFA was negatively associated. The Westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease. PMID:19766268

Lopez-Alvarenga, Juan C; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth; Voruganti, V Saroja; Comuzzie, Anthony G

2010-01-01

173

The triglyceride:high-density lipoprotein-cholesterol ratio and steno-occlusive disease in the intracranial arteries  

Microsoft Academic Search

The extent of carotid artery atherosclerosis correlates with increased plasma concentrations of total cholesterol (TC) and\\u000a low-density lipoprotein-cholesterol (LDL-C) and with a decreased plasma concentration of high-density lipoprotein-cholesterol\\u000a (HDL-C). However, emerging data suggest that a triglyceride (TG):HDL-C ratio may be a better predictor of vascular risk than\\u000a the traditional lipid measures such as TC and LDL-C. The purpose of this

Kyusik Kang; Kwangsub Lee; Sung-Hoon Chung

2011-01-01

174

Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein receptor and TG phosphorylation.  

PubMed

Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes (Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A. , and Kohn, L. D. (1997) Proc. Natl. Acad. Sci. U. S. A. 95, 8251-8256). The ability of highly purified 27, 19, or 12 S follicular TG to suppress thyroid-restricted gene expression correlates with their ability to bind to FRTL-5 thyrocytes and is inhibited by a specific antibody to the thyroid apical membrane asialoglycoprotein receptor (ASGPR), which is related to the ASGPR of liver cells. Phosphorylating serine/threonine residues of TG, by autophosphorylation or protein kinase A, eliminates TG suppression and enhances transcript levels of the thyroid-restricted genes 2-fold in the absence of a change in TG binding to the ASGPR. Follicular TG suppression of thyroid-restricted genes is thus mediated by the ASPGR on the thyrocyte apical membrane and regulated by a signal system wherein phosphorylation of serine/threonine residues on the bound ligand is an important component. These data provide a hitherto unsuspected role for the ASGPR in transcriptional signaling, aside from its role in endocytosis. They establish a functional role for phosphorylated serine/threonine residues on the TG molecule. PMID:10455190

Ulianich, L; Suzuki, K; Mori, A; Nakazato, M; Pietrarelli, M; Goldsmith, P; Pacifico, F; Consiglio, E; Formisano, S; Kohn, L D

1999-08-27

175

Pancreatic lipase hydrolysis of triglycerides by a semimicro technique  

Microsoft Academic Search

Procedures are described for rapid lipase hydrolysis of triglycerides, isolation of the hydrolytic products by TLC and their\\u000a conversion to methyl esters and fatty acid analysis by GLC. The techniques are applicable to a few mg of triglycerides or\\u000a fats. Examples of data obtained with purified triglycerides indicate that the specific action of pancreatic lipase for the\\u000a 1,3 ester groups

F. E. Luddy; R. A. Barford; S. F. Herb; P. Magidman; R. W. Riemenschneider

1964-01-01

176

Cholecystokinin Elevates Mouse Plasma Lipids  

PubMed Central

Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR?/?) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR?/? mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

Zhou, Lichun; Yang, Hong; Lin, Xinghua; Okoro, Emmanuel U.; Guo, Zhongmao

2012-01-01

177

Lab-on-a-chip for analysis of triglycerides based on a replaceable enzyme carrier using magnetic beads.  

PubMed

In this paper an enzyme-carrier-based microfluidic chip coupled with a gold nanoband microelectrode as electrochemical detector for Triglyceride (TG) determination was developed by co-immobilized lipase, Glycerokinase (GK) and glycerol-3-phosphate oxidase (GPOx) on chitosan/Fe(3)O(4) composite nanoparticles with a shell-core structure, which combined the advantageous features of microfluidic chips technology with magnetic beads. This procedure enabled the easy renewal of the microchip enzyme carrier after each determination in a highly reproducible manner. Several operational parameters such as working potential, buffer pH, adenosine triphosphate concentrations (ATP, mM), separation voltage and temperature were evaluated and optimized. The performance of enzyme-carrier-based microfluidic chip for TG determination was modulated by changing the length of enzyme carrier from 1.0 to 3.0 cm, and the linear ranges were changed from 0-4.0 mM to 0-10.0 mM with the detection limits from 15 ?M to 6.0 ?M. The enzyme carrier remained its 70% activity after 40 days storage. This system was successfully employed for on-line detection of TG in serums. The experimental results demonstrated that this enzyme carrier using magnetic beads based microfluidic chip provided a relatively simple, sensitive, miniature, and replaceable means for the accurate determination of TG in serum. PMID:20877885

Chen, Shao-Peng; Yu, Xiao-Dong; Xu, Jing-Juan; Chen, Hong-Yuan

2010-11-01

178

Bioconversion of Xylan to Triglycerides by Oil-Rich Yeasts  

PubMed Central

A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Cryptococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Cryptococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase.

Fall, Ray; Phelps, Patricia; Spindler, Diane

1984-01-01

179

Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4alpha.  

PubMed

Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipoprotein B-containing liver (e.g., VLDL) and intestinal (e.g., chylomicron) lipoproteins. The human MTP gene promoter is reported here to associate in vivo with endogenous hepatocyte nuclear factor-4alpha (HNF-4alpha) and to be transactivated or transsuppressed by overexpressed or by dominant negative HNF-4alpha, respectively. Human MTP (hMTP) transactivation by HNF-4alpha is accounted for by the concerted activity of distal (-83/-70) and proximal (-50/-38) direct repeat 1 elements of the hMTP promoter that bind HNF-4alpha. Transactivation by HNF-4alpha is specifically antagonized by chicken ovalbumin upstream promoter. Transcriptional activation of hMTP by HNF-4alpha is mediated by HNF-4alpha domains engaged in ligand binding and ligand-driven transactivation and is further complemented by HNF-4alpha/HNF-1alpha synergism that involves the HNF-4alpha activation function 1 (AF-1) domain. hMTP transactivation by HNF-4alpha is specifically inhibited by beta,beta-tetramethyl-hexadecanedioic acid acting as an HNF-4alpha antagonist ligand. hMTP transactivation by HNF-4alpha may account for the activation or inhibition of MTP expression and the production of TG-rich lipoproteins by agonist (e.g., saturated fatty acids) or antagonist [e.g., (n-3) PUFA, hypolipidemic fibrates, or Methyl-substituted dicarboxylic acid (Medica) compounds] HNF-4alpha ligands. PMID:15547294

Sheena, Vered; Hertz, Rachel; Nousbeck, Janna; Berman, Ina; Magenheim, Judith; Bar-Tana, Jacob

2005-02-01

180

Intracellular pigment epithelium-derived factor contributes to triglyceride degradation.  

PubMed

Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488

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

2013-09-01

181

Polymorphisms in genes involved in fatty acid ?-oxidation interact with dietary fat intakes to modulate the plasma TG response to a fish oil supplementation.  

PubMed

A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid ?-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid ?-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2014-01-01

182

Polymorphisms in Genes Involved in Fatty Acid ?-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation  

PubMed Central

A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid ?-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid ?-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation.

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2014-01-01

183

TG-14A Parameter Investigation (Project HAVE MOTO).  

National Technical Information Service (NTIS)

This report presents the results of Project Have MOTO which used parameter estimation to determine TG-14A stability derivatives. This test program demonstrated the ability to determine the stability derivatives using airborne flight test techniques. The U...

D. Traynor E. Leigh G. Singh M. Marlin R. Maril

2008-01-01

184

Epoxidized triglycerides as renewable monomers in photoinitiated cationic polymerization  

Microsoft Academic Search

A wide variety of epoxidized triglyceride oils was examined as renewable monomers in photoinitiated cationic polymerization. Unsaturated triglyceride oils were obtained from commercial sources and exhaustively epoxidized and characterized by chemical and spectroscopic methods. The oils were photopolymerized as thin films using diaryliodonium and triarylsulfonium salt photoinitiators bearing long-chain alkoxy substituents. The course of the photopolymerizations was monitored using differential

J. V. Crivello; R. Narayan

2009-01-01

185

Changes in liver uptake of a radioiodinated triglyceride analog in ethanol-fed rats  

SciTech Connect

A radioiodinated triglyceride (TG) analog, ({sup 125}I)-glycerol-2-palmitoyl-1,3-di-15-(p-iodophenyl)pentadecanoate (DPPG) has been synthesized and shown to accumulate within the liver of normal rats within 15 min of i.v. administration. With time, the radioactivity clears and more activity appears as the fatty acid metabolite than as parent compound. In this study, rats were fed a commercial liquid diet containing 36% of the calories either as ethanol (ET) or sucrose (CON). After six weeks, the ET rats had significantly higher plasma and liver TG levels than CON rats. In addition, the ET rats showed fatty infiltration of the liver by histopathologic examination. DPPG formulated in a detergent-saline vehicle was administered and different patterns of both uptake and clearance were seen in these groups of rats. The CON rats showed greater uptake and more rapid clearance of radioactivity than ET rats. A similar pattern was observed noninvasively by gamma camera scintigraphy. In addition, PAGE analysis of the plasma revealed that 90% of the radioactivity in the plasma was associated with plasma lipoproteins within 5 m. By 120 m 40% of the plasma activity in CON rats was associated with albumin, indicating hydrolysis to the free fatty acid. In the ET rats only 22% was albumin bound at this time. Thus, DPPG shows promise as an agent to diagnose changes in liver lipid metabolism in such disease states as alcoholism.

Schwendner, S.W.; Skinner, R.S.W.; Gross, M.; Ruyan, M.; Counsell, R.E. (Univ. of Michigan, Ann Arbor (United States) VA Medical Center, Ann Arbor, MI (United States))

1991-03-11

186

Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency.  

PubMed

Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele. PMID:16015281

Garenc, Christophe; Couillard, Charles; Laflamme, Nathalie; Cadelis, François; Gagné, Claude; Couture, Patrick; Julien, Pierre; Bergeron, Jean

2005-10-01

187

A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The treat-to-target (3T) study  

Microsoft Academic Search

Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target.Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C ?2.6

Anders G Olsson; Mats Eriksson; Owe Johnson; Thomas Kjellström; Jan Lanke; Mogens Lytken Larsen; Terje Pedersen; Matti J Tikkanen; Olov Wiklund

2003-01-01

188

Microsomal Triglyceride Transfer Protein Inhibition Induces Endoplasmic Reticulum Stress and Increases Gene Transcription via Ire1?/cJun to Enhance Plasma ALT/AST*  

PubMed Central

Microsomal triglyceride transfer protein (MTP) is a target to reduce plasma lipids because of its indispensable role in triglyceride-rich lipoprotein biosynthesis. MTP inhibition in Western diet fed mice decreased plasma triglycerides/cholesterol, whereas increasing plasma alanine/aspartate aminotransferases (ALT/AST) and hepatic triglycerides/free cholesterol. Free cholesterol accumulated in the endoplasmic reticulum (ER) and mitochondria resulting in ER and oxidative stresses. Mechanistic studies revealed that MTP inhibition increased transcription of the GPT/GOT1 genes through up-regulation of the IRE1?/cJun pathway leading to increased synthesis and release of ALT1/AST1. Thus, transcriptional up-regulation of GPT/GOT1 genes is a major mechanism, in response to ER stress, elevating plasma transaminases. Increases in plasma and tissue transaminases might represent a normal response to stress for survival.

Josekutty, Joby; Iqbal, Jahangir; Iwawaki, Takao; Kohno, Kenji; Hussain, M. Mahmood

2013-01-01

189

Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source.  

PubMed

Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans.Methods: A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (Dw,m) and dose to medium (Dm,m), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted.Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D90 to PTV was reduced by between ?4% and ?40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%-15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting.Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources. PMID:24877796

White, Shane A; Landry, Guillaume; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank; Reniers, Brigitte

2014-06-01

190

The occurrence of triglycerides in Namibian Shelf diatomaceous ooze  

NASA Astrophysics Data System (ADS)

The triglyceride fraction, isolated from extractable lipids of a diatomaceous ooze off shore Walvis Bay (S.W. Africa) by TLC methods, was analyzed by direct probe low and high resolution mass spectrometry. The mass spectral data reveal the fatty acid moieties and their relative distribution in the triglycerides identified. The C 12, C 14, C 15 and C 16 are the major composing fatty acid moieties. The triglycerides are thought to be present in protective structures such as diatom spores, which were found to be present by scanning electron microscopy.

Boon, Jaap J.; Irene, W.; Rijpstra, C.; de Leeuw, J. W.; Burlingame, A. L.

1980-01-01

191

Three months of Tai Chi Chuan exercise can reduce serum triglyceride and endothelin-1 in the elderly.  

PubMed

Endothelin-1 (ET-1) and circulating hormones play important roles in maintaining cardiovascular function. Tai Chi Chuan (TCC) is known to be good for health. This study evaluated the effect of 3 months of TCC training on serum ET-1, blood lipids, and other circulating hormones in the elderly. Twenty-two TCC trainees and 20 normal subjects were included in this study. The TCC trainees practiced classical Yang's TCC 40 min per session, 7 times per week, for 3 months. The hemodynamics and serum ET-1 and lipids before and after TCC were compared. The percentage change in serum ET-1 and triglyceride (TG) were decreased significantly after 3 months of TCC, as compared to the control group. In the TCC group, the percentage decrease in serum ET-1 and TG after 3 months of TCC were -36.6 (-63.4 to -14.0)% and -22.5 (-30.7 to 4.9)%, respectively. TCC exercise for 3 months can reduce serum ET-1 and TG in the elderly. PMID:24199974

Lu, Wan-An; Kuo, Cheng-Deng

2013-11-01

192

Development of small molecule inhibitors targeting adipose triglyceride lipase  

PubMed Central

Adipose triglyceride lipase (ATGL) is rate-limiting in the mobilization of fatty acids from cellular triglyceride stores. This central role in lipolysis marks ATGL as interesting pharmacological target since deregulated fatty acid metabolism is closely linked to dyslipidemic and metabolic disorders. Here we report on the development and characterization of a small-molecule inhibitor of ATGL. Atglistatin is selective for ATGL and reduces fatty acid mobilization in vitro and in vivo.

Romauch, Matthias; Grabner, Gernot F.; Eichmann, Thomas O.; Fuchs, Elisabeth; Ivkovic, Jakov; Heier, Christoph; Mrak, Irina; Lass, Achim; Hofler, Gerald; Fledelius, Christian; Zechner, Rudolf; Zimmermann, Robert; Breinbauer, Rolf

2013-01-01

193

High performance reversed-phase chromatography of natural triglyceride mixtures  

Microsoft Academic Search

High performance reversed-phase chromatography (HPRC) is an efficient and powerful tool gaining momentum in the separation\\u000a of triglycerides and other lipid components. In the present study the effect of different variables in triglyceride separation\\u000a has been studied. It was found that a longer hydrocarbon chain bonded to silica gel as well as the percent coverage improved\\u000a the separation. Smaller particle

A. H. El-Hamdy; E. G. Perkins

1981-01-01

194

Thujone corrects cholesterol and triglyceride profiles in diabetic rat model.  

PubMed

Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral treatment with thujone (5 mg kg?¹ body weight dose) significantly adjusted cholesterol and triglyceride levels in diabetic rats (p ? 0.05) to normal levels compared to diabetic untreated rats. This provides a premise in the field of finding new agents to treat diabetic complications. PMID:21740283

Baddar, Nour W Al-Haj; Aburjai, Talal A; Taha, Mutasem O; Disi, Ahmad M

2011-07-01

195

Triglyceride as a risk factor for coronary artery disease  

Microsoft Academic Search

The data for an independent association between triglyceride concentrations and risk for coronary artery disease (CAD) are equivocal, unlike the data for low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, which show strong, consistent, and opposing correlations with CAD risk. There is some evidence for triglyceride as an independent risk factor in certain subgroups, for example, women 50–69 years

Antonio M. Gotto

1998-01-01

196

The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression  

SciTech Connect

Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

1997-07-01

197

Fecal triglyceride excretion is not excessive in pancreatic insufficiency.  

PubMed

Steatorrhea can result from maldigestion or malabsorption. As the pathophysiology underlying impaired digestion differs from impaired absorption, it is important to differentiate these two disorders. It is generally accepted that patients with maldigestion excrete an excessive amount of triglyceride and patients with malabsorption excrete an excess of the lipolytic product of triglyceride, fatty acid. The two-step Sudan stain has been used as a simple test to differentiate these disorders. The validity of the test has not yet been established. In this study, fecal fatty acid and triglyceride were measured after extraction and thin-layer chromatographic separation. Our results indicate that in adult patients with pancreatic insufficiency, the fecal triglyceride content does not differ from the controls. However, a fivefold to sixfold increase in fecal fatty acid content in patients with pancreatic insufficiency was revealed. As patients with maldigestion do not excrete an excess of undigested triglyceride, it is not possible to differentiate maldigestion from malabsorption by quantifying fecal triglyceride and fatty acid. PMID:2464525

Khouri, M R; Ng, S N; Huang, G; Shiau, Y F

1989-03-01

198

TG69: Radiographic film for megavoltage beam dosimetry  

Microsoft Academic Search

TG-69 is a task group report of the AAPM on the use of radiographic film for dosimetry. Radiographic films have been used for radiation dosimetry since the discovery of x-rays and have become an integral part of dose verification for both routine quality assurance and for complex treatments such as soft wedges (dynamic and virtual), intensity modulated radiation therapy (IMRT),

Sujatha Pai; Indra J. Das; James F. Dempsey; Kwok L. Lam; Thomas J. Losasso; Arthur J. Olch; Jatinder R. Palta; Lawrence E. Reinstein; Dan Ritt; Ellen E. Wilcox

2007-01-01

199

Intact spatial learning in adult Tg2576 mice.  

PubMed

Tg2576 mice, a transgenic model of amyloid pathology associated with Alzheimer's disease (AD), develop measurable levels of soluble amyloid beta1-40 and 1-42 by 6 months of age and amyloid plaque deposition in cortex, hippocampus and amygdala by 10 months of age. To investigate whether non-hippocampal learning strategies would predominate coincident with the age-related increase in Abeta load in the hippocampal region, we measured learning strategies in the T-maze and a redundant cued version of the water maze. Each of these tasks can be solved using either hippocampal or non-hippocampal learning strategies and has proved sensitive to hippocampal disruption in other settings. The results revealed subtle differences in T-maze and water maze performance in Tg2576 mice compared to controls. Surprisingly, however, Tg2576 mice were not impaired relative to non-transgenic littermates on any measures of hippocampal dependent behavior assessed in these tasks. These data suggest that the medial temporal lobe retains considerable function in 15-month-old Tg2576 mice despite significant Abeta pathology. PMID:16504344

Bizon, Jennifer; Prescott, Sonya; Nicolle, Michelle M

2007-03-01

200

Simultaneous TG/DSC (Thermogravimetry/Differential Scanning Calorimetry) and TG/MS (Thermogravimetry/Mass Spectrometry) Analyses of Polymeric and Energetic Materials.  

National Technical Information Service (NTIS)

The utility of simultaneous thermal analysis techniques, such as TG/DSC and TG/MS, has been demonstrated for both energetic and polymeric materials. TG/DSC can assist in elucidating reaction mechanisms and determining weight losses for endothermic transit...

R. B. Whitaker C. R. Brown C. Chang J. A. McDaniel T. L. Shell

1987-01-01

201

Unrefined and refined black raspberry seed oils significantly lower triglycerides and moderately affect cholesterol metabolism in male Syrian hamsters.  

PubMed

Unrefined and refined black raspberry seed oils (RSOs) were examined for their lipid-modulating effects in male Syrian hamsters fed high-cholesterol (0.12% g/g), high-fat (9% g/g) diets. Hamsters fed the refined and the unrefined RSO diets had equivalently lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol in comparison with the atherogenic coconut oil diet. The unrefined RSO treatment group did not differ in liver total and esterified cholesterol from the coconut oil-fed control animals, but the refined RSO resulted in significantly elevated liver total and esterified cholesterol concentrations. The unrefined RSO diets significantly lowered plasma triglycerides (46%; P=.0126) in comparison with the coconut oil diet, whereas the refined RSO only tended to lower plasma triglyceride (29%; P=.1630). Liver triglyceride concentrations were lower in the unrefined (46%; P=.0002) and refined (36%; P=.0005) RSO-fed animals than the coconut oil group, with the unrefined RSO diet eliciting a lower concentration than the soybean oil diet. Both RSOs demonstrated a null or moderate effect on cholesterol metabolism despite enrichment in linoleic acid, significantly lowering HDL cholesterol but not non-HDL cholesterol. Dramatically, both RSOs significantly reduced hypertriglyceridemia, most likely due to enrichment in ?-linolenic acid. As a terrestrial source of ?-linolenic acid, black RSOs, both refined and unrefined, provide a promising alternative to fish oil supplementation in management of hypertriglyceridemia, as demonstrated in hamsters fed high levels of dietary triglyceride and cholesterol. PMID:21548801

Ash, Mark M; Wolford, Kate A; Carden, Trevor J; Hwang, Keum Taek; Carr, Timothy P

2011-09-01

202

Ultra high efficiency/low pressure supercritical fluid chromatography with superficially porous particles for triglyceride separation.  

PubMed

This paper reports the development of the separation of vegetable oil triglycerides (TG) in supercritical chromatography (SFC), using superficially porous particles (SPPs). The SPP, having a small diameter (2-3?m), provide a higher theoretical plate number (N), which allows to improve separation of critical pairs of compounds. However, compared to fully porous particles of larger diameter (5?m), the pressure drop is also increased. Fortunately, supercritical fluids have a low viscosity, which allows coupling several columns to achieve high N values, while maintaining flow rate above 1ml/min, ensuring a ultra high efficiency (UHE) at low pressure (LP) (below 40MPa), with regards to the one reached with liquid and sub-two micron particles (around 100MPa). The use of two detector systems (UV and ELSD) connected in series to the UHE-LP-SFC system provides complementary responses, due to their specific detection principles. Working in a first part with three coupled Kinetex C18 columns (45cm total length), the effect of modifier nature and percentage were studied with two reference oils, argan and rapeseed, chosen for their different and well-known TG composition. The analytical method was developed from previous studies performed with fully porous particles (FPP). Optimized conditions with three Kinetex were as follows: 17°C, 12% of ACN/MeOH (90/10; v/v). With these conditions, and by using an increased length of Kinetex C18 column (60cm), another additional column was selected from ten different commercial SPP C18 bonded phases, by applying a Derringer function on varied parameters: theoretical plate number (TPN), separation index (SI) for critical pairs of peaks (the peaks of compounds difficult to separate due to subtle structural differences), the analysis duration, and the total peak number. This function normalizes the values of any parameters, between 0 and 1, from the worst value to the better, allowing to take account of various parameters in the final choice. Finally, by using four Kinetex C18 plus one Accucore C18 (75cm total column length), a high-performance separation of triglycerides was achieved, with reasonable analysis duration and isocratic conditions. These conditions can be applied to varied vegetable oils. Identification of the numerous separated peaks of rapeseed oil was achieved by using published data and chromatographic retention behaviour. PMID:24411089

Lesellier, E; Latos, A; de Oliveira, A Lopes

2014-01-31

203

Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-?, IL6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats  

Microsoft Academic Search

Chromium (Cr3+) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-?, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA1), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats

Sushil K. Jain; Justin L. Rains; Jennifer L. Croad

2007-01-01

204

Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci  

PubMed Central

Background The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. Methods and Findings We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4,361) and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein (NPC1) gene (P=2.43×10?08). Furthermore, three European loci for TGs (APOA5, GCKR, and LPL) and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We utilized cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalized to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. Conclusions This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; utilized the inter-population heterogeneity to significantly restrict three previously known European GWA signals; and surveyed whether the European lipid GWA SNPs extend to the Mexican population.

Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A.; Nikkola, Elina; Deere, Kerry A.; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Munoz-Hernandez, Linda Liliana; Gomez-Munguia, Lizeth; Ordonez-Sanchez, Maria Luisa; Reddy, Prasad MV Linga; Lusis, Aldons J.; Matikainen, Niina; Taskinen, Marja-Riitta; Riba, Laura; Cantor, Rita M.; Sinsheimer, Janet S.; Tusie-Luna, Teresa; Pajukanta, Paivi

2013-01-01

205

Changes in serum triglycerides and high-density lipoprotein concentration and composition after a low-fat mixed meal. Effects of gender and insulin resistance  

Microsoft Academic Search

Objective  Postprandial lipaemia is generally studied after a test meal that provides most of the calories as fat and that does not reflect\\u000a the common food intake. We investigated postprandial changes in serum triglycerides (TG) and in high-density lipoprotein (HDL)\\u000a concentration and composition after a regular meal poor in fat (30% of calories).\\u000a \\u000a \\u000a \\u000a Methods  Fifty-four women and 54 men had breakfast at

Adriana Branchi; Adriana Torri; Cristina Berra; Emanuela Colombo; Domenico Sommariva

2006-01-01

206

Identification of benzophenone C-glucosides from mango tree leaves and their inhibitory effect on triglyceride accumulation in 3T3-L1 adipocytes.  

PubMed

A 70% ethanol-water extract from the leaves of Mangifera indica L. (Anacardiaceae) inhibited triglyceride (TG) accumulation in 3T3-L1 cells. From the active fraction, seven new benzophenone C-glycosides, foliamangiferosides A (1), A(1) (2), A(2) (3), B (4), C(1) (5), C(2) (6), and C(3) (7), together with five known compounds were isolated and the structures were elucidated on the basis of chemical and physicochemical evidence. The effects of these compounds on TG and the free fatty acid level in 3T3-L1 cells were determined, and the structure-activity relationship was discussed. On the basis of the AMPK signaling pathway, several compounds were found to increase the AMPK enzyme expression and down-regulate lipogenic enzyme gene expression such as SREBP1c, FAS, and HSL. PMID:21923172

Zhang, Yi; Qian, Qian; Ge, Dandan; Li, Yuhong; Wang, Xinrui; Chen, Qiu; Gao, Xiumei; Wang, Tao

2011-11-01

207

Isolation, structural elucidation, MS profiling, and evaluation of triglyceride accumulation inhibitory effects of benzophenone C-glucosides from leaves of Mangifera indica L.  

PubMed

Seventy percent ethanol-water extract from the leaves of Mangifera indica L. (Anacardiaceae) was found to show an inhibitory effect on triglyceride (TG) accumulation in 3T3-L1 cells. From the active fraction, six new benzophenone C-glucosides, foliamangiferosides A(3) (1), A(4) (2), C(4) (3), C(5) (4), C(6) (5), and C(7) (6) together with 11 known benzophenone C-glucosides (7-17) were obtained. In this paper, isolation, structure elucidation (1-6), and MS fragment cleavage pathways of all 17 isolates were studied. 1-6 showed inhibitory effects on TG and free fatty acid accumulation in 3T3-L1 cells at 10 ?M. PMID:23368644

Zhang, Yi; Han, Lifeng; Ge, Dandan; Liu, Xuefeng; Liu, Erwei; Wu, Chunhua; Gao, Xiumei; Wang, Tao

2013-02-27

208

Acoustic detection and localization from a tethered aerostat during the NATO TG-53 test  

NASA Astrophysics Data System (ADS)

Acoustic sensors mounted to a tethered aerostat detect and localize transient signals from mortars, artillery, C-4, propane cannon, and small arms fire. Significant enhancements to soldier lethality and survivability can be gained when using the aerostat array to detect, localize, and cue an aerial imager to a weapon's launch site, or use the aerostat's instantaneous position and orientation to calculate a vector solution to the ground coordinates of the launch site for threat neutralization. The prototype aerostat-mounted array was tested at Yuma Proving Grounds (YPG) as part of the NATO TG-53 signature collection exercise. Acoustic wave form data was collected simultaneously with aerostat and ground-based sensor arrays for comparing wind noise, signal to noise related parameters, and atmospheric effects on propagation to an elevated array. A test description and summary of localization accuracy will be presented for various altitudes, ranges to target, and under differing meteorological conditions.

Reiff, C.; Scanlon, M.; Noble, J.

2006-06-01

209

A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons.  

PubMed

The brain depends on redox electrons from nicotinamide adenine dinucleotide (reduced form; NADH) to produce ATP and oxyradicals (reactive oxygen species [ROS]). Because ROS damage and mitochondrial dysregulation are prominent in aging and Alzheimer's disease (AD) and their relationship to the redox state is unclear, we wanted to know whether an oxidative redox shift precedes these markers and leads to macromolecular damage in a mouse model of AD. We used the 3xTg-AD mouse model, which displays cognitive deficits beginning at 4 months. Hippocampal/cortical neurons were isolated across the age span and cultured in common nutrients to control for possible hormonal and vascular differences. We found an increase of NAD(P)H levels and redox state in nontransgenic (non-Tg) neurons until middle age, followed by a decline in old age. The 3xTg-AD neurons maintained much lower resting NAD(P)H and redox states after 4 months, but the NADH regenerating capacity continuously declined with age beginning at 2 months. These redox characteristics were partially reversible with nicotinamide, a biosynthetic precursor of NAD+. Nicotinamide also protected against glutamate excitotoxicity. Compared with non-Tg neurons, 3xTg-AD neurons had more mitochondria/neuron and lower glutathione (GSH) levels that preceded age-related increases in ROS levels. These GSH deficits were again reversible with nicotinamide in 3xTg-AD neurons. Surprisingly, low macromolecular ROS damage was only elevated after 4 months in the 3xTg-AD neurons if antioxidants were removed. The present data suggest that a more oxidized redox state and a lower antioxidant GSH defense can be dissociated from neuronal ROS damage, changes that precede the onset of cognitive deficits in the 3xTg-AD model. PMID:22539844

Ghosh, Debolina; LeVault, Kelsey R; Barnett, Aaron J; Brewer, Gregory J

2012-04-25

210

Mitochondrial bioenergetics is defective in presymptomatic Tg2576 AD mice  

PubMed Central

Alzheimer’s disease (AD) is an age-related dementia, with the pathological hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as a contributing factor to the cognitive decline observed in AD. We hypothesized that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial respiration is impaired early in synaptic terminals, which are vital to cognitive performance, preferentially in cognitive centers of the brain. We compared oxygen consumption in synaptosomal and perikaryal mitochondria prepared from the cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice. Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in the cerebral cortex specifically in synaptosomal fraction, while the perikaryal mitochondria were unaffected. Neither mitochondrial fraction was affected in the cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic defect in synaptic terminals of mice overexpressing mutant beta-amyloid, in particular in an area of the brain important to cognition, points to an early role of mitochondrial defects in the onset of cognitive deficits in AD.

Varghese, Merina; Zhao, Wei; Wang, Jun; Cheng, Alice; Qian, Xianjuan; Chaudhry, Amna; Ho, Lap; Pasinetti, Giulio Maria

2012-01-01

211

Serum cholesterol and triglyceride levels in Norwegian adolescent school children.  

PubMed

The frequency distribution of serum cholesterol and triglycerides in 172 boys and 232 girls, 13--16 years, from four elementary schools in Oslo has been determined. The cholesterol values were significantly higher for girls 15--16 years than for boys of the same age group. In the case of triglycerides boys 15--16 years had significantly higher values than boys 13--14 years. Otherwise no statistically significant differences with regard to sex and age were observed. The 85th percentiles have been suggested as appropriate upper normal limits. In all groups the 85th percentile for plasma cholesterol was slightly below 6 mmol/l. The corresponding plasma triglyceride value was below 2 mmol/l. PMID:626074

Askevold, R; Høstmark, A T; Vellar, O D; Von Kraemer Bryn, M; Glattre, E

1978-03-01

212

Chronic Temporal Lobe Epilepsy Is Associated with Enhanced Alzheimer-Like Neuropathology in 3xTg-AD Mice  

PubMed Central

The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of growing interest. Senile plaques and tauopathy are found in epileptic human temporal lobe structures, and individuals with AD have an increased incidence of spontaneous seizures. However, why and how epilepsy is associated with enhanced AD-like pathology remains unknown. We have recently shown ?-secretase-1 (BACE1) elevation associated with aberrant limbic axonal sprouting in epileptic CD1 mice. Here we sought to explore whether BACE1 upregulation affected the development of Alzheimer-type neuropathology in mice expressing mutant human APP, presenilin and tau proteins, the triple transgenic model of AD (3×Tg-AD). 3×Tg-AD mice were treated with pilocarpine or saline (i.p.) at 6–8 months of age. Immunoreactivity (IR) for BACE1, ?-amyloid (A?) and phosphorylated tau (p-tau) was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed of BACE1-labeled swollen/sprouting axons and extracellular A?IR were seen in the hippocampal formation, amygdala and piriform cortices of 9 month-old epileptic, but not control, 3×Tg-AD mice. Densities of plaque-associated BACE1 and A?IR were elevated in epileptic versus control mice at 11 and 14 months of age. p-Tau IR was increased in dentate granule cells and mossy fibers in epileptic mice relative to controls at all time points examined. Thus, pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced neuritic plaque formation and altered intraneuronal p-tau expression in temporal lobe structures in 3×Tg-AD mice, with these pathologies occurring in regions showing neuronal death and axonal dystrophy.

Yan, Xiao-Xin; Cai, Yan; Shelton, Jarod; Deng, Si-Hao; Luo, Xue-Gang; Oddo, Salvatore; LaFerla, Frank M.; Cai, Huaibin; Rose, Gregory M.; Patrylo, Peter R.

2012-01-01

213

Triglyceride accumulation and altered composition of triglyceride-associated fatty acids in the skin of tenascin-X-deficient mice.  

PubMed

Tenascin-X (TNX) is a member of the tenascin family of glycoproteins of the extracellular matrix. Here, we observed abnormalities in the skin of TNX-deficient mice in comparison with that of wild-type mice. Histological analysis with Oil Red O staining demonstrated that there was considerable accumulation of lipid in the skin of TNX-deficient (TNX-/-) mice. By thin-layer chromatography of total lipids, it was found that the level of triglyceride was significantly increased in TNX-/- mice. The mRNA levels of most of the lipogenic enzyme genes examined were remarkably increased in TNX-/- mice. By gas chromatography-mass spectrometry analysis of triglyceride-associated fatty acids in the skin, saturated fatty acid palmitoic acid was decreased, whereas unsaturated fatty acids palmitoleic acid and oleic acid were increased in TNX-/- mice compared with those in wild-type mice. Conversely, fibroblast cell lines transfected with TNX showed a significant decrease in the amount of triglyceride. An increase in the saturated fatty acid stearic acid and decreases in the unsaturated fatty acids palmitoleic acid, oleic acid and linoleic acid, compared to those in mock-transfected cells were also caused by over-expression of TNX. These results indicate that TNX is involved in the regulation of triglyceride synthesis and the regulation of composition of triglyceride-associated fatty acids. PMID:15298681

Matsumoto, Ken-ichi; Sato, Takashige; Oka, Seiko; Orba, Yasuko; Sawa, Hirofumi; Kabayama, Kazuya; Inokuchi, Jin-ichi; Ariga, Hiroyoshi

2004-08-01

214

Polymorphism and transformation energetics of saturated monoacid triglycerides from differential scanning calorimetry and theoretical modeling  

Microsoft Academic Search

Differential scanning calorimetry studies on saturated monoacid triglycerides were extended to include most odd and even chain\\u000a lengths from tricaprylin (C8) through tritriacontanoin (C30). Two ?’-forms were common with triglycerides C15 through C24: shorter odd chain length triglycerides (C9-C13) exhibited only one ?’-form; short even chain length triglycerides (C8-C14) exhibited three. Odd chain length C21 and C23 triglycerides showed two

J. W. Hagemann; J. A. Rothfus

1983-01-01

215

Vector Percolation Analysis of Triglyceride-based Thermoset Polymers  

NASA Astrophysics Data System (ADS)

Thermosetting Acrylated triglycerides (ATG) were prepared from various oils and model triglycerides. The distribution of acrylate groups was calculated from the distribution of unsaturation sites on unmodified oils, assuming a binomial distribution of acrylate groups. The ATG were both homopolymerized and copolymerized with styrene. The cross-link density v, of the polymers was calculated using the recursive method of Miller and Macosko from a knowledge of the acrylate distribution. The cross-link density was found to increase with the level of acrylation A, in a vector percolation manner, and the trends in the cross-link density predictions matched the experimental results. The deviation in the experimental results and model predictions were the result of intramolecular cross-linking. Approximately 0.5 and 0.8 acrylates per triglyceride were lost to intramolecular cyclization for homopolymerized acrylated triglycerides and triglycerides copolymerized with styrene, respectively. Equations for the level of perfection p, of the triglyceride networks and the percolation threshold pc, were developed using the calculated number of acrylates lost to cyclization. Polymers with p < 0.1 without styrene, and p < 0.39 with styrene did not have mechanical integrity, validating the definition of the level of perfection and percolation threshold pc. The tensile strength, S ˜ [p-p]^1/2 and modulus E ˜ [p-pc]^3 , were in accord with vector percolation theory, where p could be derived experimentally via A ˜ [p-pc] , v ˜ A and FTIR analysis of the extent of reaction of the C=C groups. These results also indicated how mechanical properties were controlled by the fatty acid distribution function of the plant oils, and which oil would give the best particular property. Supported by EPA and DoE.

Lascala, John J.; Wool, Richard P.

2003-03-01

216

Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus Physalis  

PubMed Central

Background In folklore, some people take the decoction of Calyx seu Fructus Physalis (CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material. Methods CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the in vivo and in vitro models of hyperlipidemia were utilized. The structure of active component was determined by 13 C-NMR and 1H-NMR. Results The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid in vivo and in vitro experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain. Conclusion Our results demonstrated that the 75% ethanol extract of CSFP could improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids.

2012-01-01

217

Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase & horseradish peroxidase onto plasticized polyvinyl chloride (PVC) strip & its application in serum triglyceride determination  

PubMed Central

Background & objectives: Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG) suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. Methods: A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. Results: The enzyme-strip showed optimum activity at pH 7.0, 35°C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99) was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4°C. Interpretation & conclusions: The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also.

Chauhan, Nidhi; Narang, Jagriti; Pundir, Chandra Shekhar

2014-01-01

218

Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase & horseradish peroxidase onto plasticized polyvinyl chloride (PVC) strip & its application in serum triglyceride determination.  

PubMed

Background & objectives:Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG) suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. Methods: A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK), glycerol-3-phosphate oxidase (GPO) and peroxidase (HRP) directly onto plasticized polyvinyl chloride (PVC) strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. Results: The enzyme-strip showed optimum activity at pH 7.0, 35 o C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV) were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99) was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4 o C. Interpretation & conclusions: The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also. PMID:24927348

Chauhan, Nidhi; Narang, Jagriti; Pundir, Chandra Shekhar

2014-04-01

219

Quantitative gas liquid chromatographic analysis of butterfat triglycerides  

Microsoft Academic Search

Gas liquid chromatographic triglyceride separation by carbon number, and integration of the area response obtained in the\\u000a hydrogen flame ionization detector, has permitted the calculation of the following molar proportions for the various triglyceride\\u000a types in a blended butterfat sample: C24 0.5, C25 0.08, C26 0.57, C27 0.18, C28 0.81, C29 0.17, C30 1.15, C31 0.2, C32 3.1, C33 0.34,

A. Kuksis; M. J. McCarthy; J. M. R. Beveridge

1963-01-01

220

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue  

PubMed Central

Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo.

Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

2013-01-01

221

Application of Constant Reaction Rate TG to the Determination of Kinetic Parameters by Hi-Res TG  

Microsoft Academic Search

A simple operation mode to determine the apparent activation energy E\\u000a a is introduced. E\\u000a a can be determined with a double-curve method by using a constant reaction rate (CRR) approach of Hi-Res TG. The most appropriate\\u000a mechanism function f(?) and frequency factor A are determined by a single-curve method when the activation energies provided by the two methods are

X. E. Cai; H. Shen; C. H. Zhang; Y. X. Wang; Z. Kong

2000-01-01

222

Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels.  

PubMed

Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey, and tested for evidence of interactions with waist circumference. We conducted additional association and interaction analyses in 1,719 of their young adult offspring. Genome-wide significant associations (P < 5 × 10??) were detected at APOE for low density lipoprotein cholesterol and total cholesterol, and at APOA5 for TGs. Suggestive associations (P < 10??) were detected at GCKR for TGs, and at CETP and TOM1 for high density lipoprotein cholesterol. Our data also supported the existence of allelic heterogeneity at APOA5, CETP, LIPC, and APOE. The secondary signal (Gly185Cys) at APOA5 exhibited a single nucleotide polymorphism (SNP)-by-waist circumference interaction affecting TGs (Pinteraction = 1.6 × 10??), manifested by stronger SNP effects as waist circumference increased. These findings provide the first evidence that central obesity may accentuate the effect of the TG-increasing allele of the APOA5 signal, emphasizing that CVD risk could be reduced by central obesity control. PMID:24023260

Wu, Ying; Marvelle, Amanda F; Li, Jin; Croteau-Chonka, Damien C; Feranil, Alan B; Kuzawa, Christopher W; Li, Yun; Adair, Linda S; Mohlke, Karen L

2013-11-01

223

In vivo clearance of chylomicron triglycerides containing w-3 eicosapentaenoic acid  

SciTech Connect

The in vivo clearance of chylomicron triglycerides (TG) enriched in either oleic acid (OA) or w-3 eicosapentaenoic acid (EPA) was compared. Chylomicrons were obtained from the mesenteric lymph (0-6 h) of rats, administered either 0.3 mM (1-/sup 14/C) OA or (1-/sup 14/C) EPA as an intraduodenal aqueous emulsion. The chylomicrons enriched with (1-/sup 14/C) OA or (1-/sup 14/C) EPA were isolated and purified by ultracentrifugation, and were injected into the jugular vein of recipient anesthetized rats. There was no significant difference between the two groups when total serum radioactivity was compared at 2, 5, and 10 min. However, at 25, 60, and 90 min, the clearance of EPA-enriched chylomicrons was significantly slower (P < 0.05). At each time analyzed the distribution of (/sup 14/C) oleic acid and of EPA among serum lipoproteins was comparable. After 5 min of chylomicron infusion the d < 1.006 g/ml lipoproteins contained almost 90% of the injected chylomicron radioactivity, while by 240 min, this fraction retained 42% of the remaining isotope. These and earlier studies suggested that the absorption and chylomicron transport of EPA in the intestine is not unusual, and that clearance of EPA-enriched chylomicrons may be only slightly slower than those enriched with oleate.

Chen, I.S.; Satchithanandum, S.; Cassidy, M.M.; Sheppard, A.J.; Vahouny, G.V.

1986-03-01

224

Impact of perturbed pyruvate metabolism on adipocyte triglyceride accumulation.  

PubMed

This study aimed to test the hypothesis that adipocyte TG accumulation could be altered by specifically perturbing pyruvate metabolism. We treated cultured 3T3-L1 adipocytes with chemical inhibitors of lactate dehydrogenase (LDH) and pyruvate carboxylase (PC), and characterized their global effects on intermediary metabolism using metabolic flux and isotopomer analysis. Inhibiting the enzymes over several days did not alter the adipocyte differentiation program as assessed by the expression levels of peroxisome proliferator-activated receptor-gamma and glycerol-3-phosphate dehydrogenase. The main metabolic effects were to up-regulate intracellular lipolysis and decrease TG accumulation. Inhibiting PC also up-regulated glycolysis. Flux estimates indicated that the reduction in TG was due to decreased de novo fatty acid synthesis. Exogenous addition of free fatty acids dose-dependently increased the cellular TG level in the inhibitor-treated adipocytes, but not in untreated control cells. The results of this study support our hypothesis regarding the critical role of pyruvate reactions in TG synthesis. PMID:19683593

Si, Yaguang; Shi, Hai; Lee, Kyongbum

2009-11-01

225

location plan, floor plan, west elevation, north elevation, north elevation ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

location plan, floor plan, west elevation, north elevation, north elevation with porch removed - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Staff Quarters, Prince William Forest Park, Triangle, Prince William County, VA

226

Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance  

PubMed Central

Fatty acid oversupply is a key mediator of skeletal muscle insulin resistance in obesity, primarily via accumulation of fatty acid metabolites and activation of proinflammatory pathways. Herein, we demonstrate that fatty acid–induced insulin resistance in humans is completely prevented the day after 1 session of endurance exercise. Because skeletal muscle is the primary site for systemic glucose disposal and is highly susceptible to impaired insulin action by elevated fatty acid availability, we obtained skeletal muscle samples to investigate possible mechanisms mediating this protective effect of exercise. Prevention of fatty acid–induced insulin resistance after exercise accompanied enhanced skeletal muscle protein expression of key lipogenic enzymes and an increase in muscle triglyceride synthesis. Partitioning more fatty acids toward triglyceride synthesis within muscle reduced the accumulation of fatty acid metabolites and suppressed the proinflammatory response in skeletal muscle, as evidenced by decreased phosphorylation and activation of JNK and increased abundance of inhibitor of NF-?B ? (I?B-?) and I?B-?. We believe this is the first study to demonstrate that 1 session of exercise completely reverses fatty acid–induced insulin resistance in humans. Reversal of insulin resistance accompanied enhanced lipogenic capacity within skeletal muscle, reduced accumulation of highly bioactive fatty acid metabolites, and suppressed activation of proinflammatory pathways known to impair insulin action.

Schenk, Simon; Horowitz, Jeffrey F.

2007-01-01

227

The conjoint trait of low high-density lipoprotein cholesterol and high triglycerides in adolescent black and white males.  

PubMed

To evaluate the interrelationships among body composition, blood pressure, and lipid phenotypes in adolescent black and white boys, we assessed racial distributions of lipids, blood pressure, and obesity and their joint occurrence in black and white boys aged 10 to 15 years. Subjects were recruited from Cincinnati (OH) schools. Because the differences in high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) are the most profound coronary heart disease (CHD) risk factor differences between black and white males, we assigned subjects to one of four low-HDL-C and high-TG categories (normal and increased risk) using the age/race-specific 25th (HDL-C) and 75th (TG) percentiles. We then assessed racial distributions of lipids, blood pressure, and obesity by these phenotypes. Age differences between the black and white participants were significant, with the former about 3 months younger (P=.03), but black boys were more mature and were significantly taller and heavier and had a greater body mass index ([BMI] weight in kilograms divided by height in centimeters squared). Differences in the sum of the triceps, subscapular, and suprailiac skinfolds were not significant. Blacks had significantly higher HDL-C, lower TG, and higher diastolic blood pressure (DBP), but differences in systolic blood pressure (SBP) were not significant. In both racial groups, the body composition measures were significantly correlated with HDL-C, TG, and blood pressure levels; the correlations between HDL-C and both weight and BMI were significantly stronger in white boys. The proportion of boys of each race with low HDL-C and high TG was similar by design. In both racial groups, subjects with the conjoint trait had a significantly greater BMI, triceps skinfold, and sum of skinfolds than subjects in the other phenotypic groups. For white boys, participants with the conjoint trait had the highest SBP and DBP; differences in SBP were significant for comparisons to the normal- and high-TG group alone, and differences in DBP were significant for the comparison between normal and low HDL-C alone. For black boys, subjects with both normal HDL-C and TG had significantly lower SBP than boys with either the conjoint trait or high TG alone; none of the group differences in DBP were significant. Black had significantly less dense LDL (more LDL-C per apolipoprotein [apo] B). In each racial group, boys with the conjoint trait had the most dense LDL, significantly more dense than in any of the other phenotypes in black boys and significantly more dense than in boys with low HDL-C alone and normal boys in the white group. In both racial groups, the occurrence of no risk factors (>75th percentile TG, BMI, SBP, and DBP or <25th percentile HDL-C) and three or more risk factors was greater than expected by chance alone, and the occurrence of exactly one risk factor and two factors was less. When examined by phenotypic groups within race, boys in each racial group with the normal phenotype had a greater than expected percentage with no risk factors, and white boys with the conjoint trait were more likely to have a marked increase in multiple risk factors. Possible mechanisms for this clustering of risk factors and for the racial differences in the patterns are discussed. PMID:9591740

Morrison, J A; Barton, B A; Biro, F M; Sprecher, D L

1998-05-01

228

Elevated transglutaminase 2 activity is associated with hypoxia-induced experimental pulmonary hypertension in mice.  

PubMed

Previous studies in human patients and animal models have suggested that transglutaminase 2 (TG2) is upregulated in pulmonary hypertension (PH), a phenomenon that appears to be associated with the effects of serotonin (5-hydroxytryptamine; 5-HT) in this disease. Using chemical tools to interrogate and inhibit TG2 activity in vivo, we have shown that pulmonary TG2 undergoes marked post-translational activation in a mouse model of hypoxia-induced PH. We have also identified irreversible fluorinated TG2 inhibitors that may find use as non-invasive positron emission tomography probes for diagnosis and management of this debilitating, lifelong disorder. Pharmacological inhibition of TG2 attenuated the elevated right ventricular pressure but had no effect on hypertrophy of the right ventricle of the heart. A longitudinal study of pulmonary TG2 activity in PH patients is warranted. PMID:24152195

DiRaimondo, Thomas R; Klöck, Cornelius; Warburton, Rod; Herrera, Zachary; Penumatsa, Krishna; Toksoz, Deniz; Hill, Nicholas; Khosla, Chaitan; Fanburg, Barry

2014-01-17

229

Effects of Bean Meal on Serum Cholesterol and Triglycerides.  

National Technical Information Service (NTIS)

The effects of a bean diet on serum cholesterol and triglycerides were investigated in 123 cases with hyperlipidemia. The subjects were asked to take a meal of beans containing 50-100 gm of whole beans (including Phaseolus vulgaris L, Phaseolus radiatus L...

B. Liu Z. Wu W. Liu R. Zhang

1981-01-01

230

Triglyceride accumulation protects against fatty acid-induced lipotoxicity  

Microsoft Academic Search

Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic -cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess

Laura L. Listenberger; Xianlin Han; Sarah E. Lewis; Sylvaine Cases; Robert V. Farese Jr.; Daniel S. Ory; Jean E. Schaffer

2003-01-01

231

A risk factor for atherosclerosis: triglyceride-rich lipoproteins.  

PubMed

Compelling evidence from meta-analysis of a number of clinical studies on a large aggregate of patients has established an increased level of triglycerides as an independent risk factor for atherosclerotic heart disease. The finding of triglyceride-rich lipoproteins in human atheromata has provided substantial pathophysiologic evidence for a direct role in atherogenesis. Hypertriglyceridemia is commonly embedded in the context of a metabolic syndrome that includes central obesity, insulin resistance, low levels of HDL cholesterol, and often hypertension. Hypertriglyceridemia also appears to underlie the phenomenon of small dense LDL in most instances. Therapeutic interventions must be directed at underlying obesity, insulin resistance, and diabetes when present, as well as addressing metabolic determinants of dyslipidemia per se. Diet, exercise, weight loss, and avoidance of alcohol are the cornerstones of treatment. The choice of medication should be based on the lipoprotein phenotype. Niacin, fibric acid derivatives, and omega-3 fatty acids are most useful in treating severe hypertriglyceridemia. HMG-CoA reductase inhibitors are useful in some phenotypes with moderately increased triglyceride levels. Evidence from a number of clinical trials indicates that mitigation of risk of coronary heart disease, and possibly stroke, can be effected by reducing levels of plasma triglycerides. PMID:11795072

Malloy, M J; Kane, J P

2001-01-01

232

Construction of an amperometric TG biosensor based on AuPPy nanocomposite and poly (indole-5-carboxylic acid) modified Au electrode.  

PubMed

A method is described for construction of an amperometric triglyceride (TG) biosensor based on covalent co-immobilization of lipase, glycerol kinase and glycerol-3-phosphate oxidase onto gold polypyrrole nanocomposite decorated poly indole-5-carboxylic acid electrodeposited on the surface of a gold electrode. The enzyme electrode was characterized by transmission electron microscopy, scanning electron microscopy, electrochemical impedance studies, Fourier transform infrared spectroscopy and cyclic voltammetry. Biosensor showed optimum response within 4 s at pH 6.5 and 35 °C, when polarized at +0.1 V against Ag/AgCl. There was a linear relationship between sensor response and triolein concentration in the range 50-700 mg/dl. Biosensor was employed for determination of TG in serum. Detection limit of the biosensor was 20 mg/dl. Biosensor was evaluated with 91-95 % recovery of added triolein in sera and 4.14 and 5.85 % within and between batch coefficients of variation, respectively. There was a good correlation (r = 0.99) between sera TG values by standard method (Enzymic colorimetric) and the present method. The biosensor was unaffected by a number of serum substances at their physiological concentration. Biosensor lost 50 % of its initial activity after its 100 uses over 7 months, when stored at 4 °C. PMID:22903594

Narang, Jagriti; Chauhan, Nidhi; Rani, Poonam; Pundir, C S

2013-04-01

233

Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.  

PubMed

Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr(372) resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr(372) eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr(372) to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon ?-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr(372) as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391

Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

2014-06-15

234

TG-FTIR methods for the evaluation on lubricant contamination  

SciTech Connect

A typical Air Force base will produce several thousand gallons per year of used turbine engine lubricants. The potential for contamination of the collected lubricants, particularly with halogenated, compounds such as decreasing solvents and other fluids, reduces the effectiveness of a previously developed reclamation process. In this project, the feasibility of using two different thermally analysis methods in combination with advanced data analysis techniques to detect contamination in used turbine engine lubricants was investigated. The first method, TG/FT-IR combined with advanced data analysis routines, was shown to be capable of detecting the presence of several different types of contaminants in synthetic lubricants at concentrations of about 5%. It was demonstrated that data analysis routines based on factor analysis (SIMCA) and neural networks could be used for identifying the presence of a contaminant. The second method, TG/secondary oxidation/FT-IR, was developed specifically for detecting trace levels of chlorinated contaminants in lubricants. Optimization of this method using existing instrumentation led to a detection limit of about 300 ppm (w/w) organic chlorine in the lubricant. Further improvements in hardware and software components could lead to detection limits of <10 ppm. This instrumentation could also be used to characterize used motor oils, cooking oils or pyrolysis oils.

Bonanno, A.S.; Bassilakis, R.; Serio, M.A. [Advanced Fuel Research, Inc., East Hartford, CT (United States)

1996-12-31

235

Relationships between serum lipid, lipoprotein, triglyceride-rich lipoprotein, and high-density lipoprotein particle concentrations in post-renal transplant patients*  

PubMed Central

Objective: Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods: Serum levels of lipids, lipoprotein, triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL) particles were determined, lipid and lipoprotein ratios were calculated, and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Tx patients had disturbed concentration, composition, and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios, which indicates that both ratios could sensitively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients, the decreased HDL-C/apoAI ratio indicates that, along with the decreased apoAI concentration, the HDL-C level is decreased. However, a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio), and thus are hypercatabolized and removed; therefore, concentration of HDL particles in serum was decreased. Conclusion: The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.

Kimak, Elzbieta; Halabis, Magdalena; Baranowicz-Gaszczyk, Iwona

2010-01-01

236

Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.  

PubMed Central

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines.

Winter, B. K.; Fiskum, G.; Gallo, L. L.

1995-01-01

237

TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content.  

PubMed

Genome-wide association studies have identified a locus on chromosome 19 associated with plasma triglyceride (TG) concentration and nonalcoholic fatty liver disease. However, the identity and functional role of the gene(s) responsible for these associations remain unknown. Of 19 expressed genes contained in this locus, none has previously been implicated in lipid metabolism. We performed gene expression studies and expression quantitative trait locus analysis in 206 human liver samples to identify the putative causal gene. Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown function, expressed predominantly in liver and intestine, was identified as the putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7-10 predicted transmembrane domains. Otherwise, no other protein features were identified which could help to elucidate the function of TM6SF2. Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells. Functional studies for secretion of TG-rich lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and overexpression techniques. In agreement with the genome-wide association data, it was found that TM6SF2 siRNA inhibition was associated with reduced secretion of TRLs and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content. PMID:24927523

Mahdessian, Hovsep; Taxiarchis, Apostolos; Popov, Sergej; Silveira, Angela; Franco-Cereceda, Anders; Hamsten, Anders; Eriksson, Per; Van't Hooft, Ferdinand

2014-06-17

238

TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content  

PubMed Central

Genome-wide association studies have identified a locus on chromosome 19 associated with plasma triglyceride (TG) concentration and nonalcoholic fatty liver disease. However, the identity and functional role of the gene(s) responsible for these associations remain unknown. Of 19 expressed genes contained in this locus, none has previously been implicated in lipid metabolism. We performed gene expression studies and expression quantitative trait locus analysis in 206 human liver samples to identify the putative causal gene. Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown function, expressed predominantly in liver and intestine, was identified as the putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7–10 predicted transmembrane domains. Otherwise, no other protein features were identified which could help to elucidate the function of TM6SF2. Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells. Functional studies for secretion of TG-rich lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and overexpression techniques. In agreement with the genome-wide association data, it was found that TM6SF2 siRNA inhibition was associated with reduced secretion of TRLs and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content.

Mahdessian, Hovsep; Taxiarchis, Apostolos; Popov, Sergej; Silveira, Angela; Franco-Cereceda, Anders; Hamsten, Anders; Eriksson, Per; van't Hooft, Ferdinand

2014-01-01

239

Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.  

PubMed

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines. PMID:7577464

Winter, B K; Fiskum, G; Gallo, L L

1995-11-01

240

Fasting Blood Sugar and Serum Triglyceride as the Risk Factors of Colorectal Adenoma in Korean Population Receiving Screening Colonoscopy  

PubMed Central

In several previously reported studies, metabolic syndrome (MS) was found to be associated with colorectal adenomas. While the incidence of colorectal adenoma is growing in Korean population, there are only few studies that examined the association between MS and colorectal adenoma in Korea. The aim of this study was to investigate relationships between prevalence of colorectal adenoma and MS components. We conducted a cross sectional study using data from individuals who had undergone complete colonoscopy for health examinations at the Health Promotion Center of Korea University Medical Center from July 1, 2004 to July 31, 2010. A total of 7481 subjects (4459 males and 3022 females) were included; 1733 subjects with pathologically proven adenoma were assigned to the case group, and other 5748 subjects were assigned to the non-case group. All the participants underwent colonoscopy and received blood biochemical tests (fasting blood sugar [FBS], insulin, lipid profile, hemoglobin, blood urea nitrogen [BUN], creatinine). Univariate analysis showed that the prevalence of colorectal adenoma was higher in individuals with higher blood pressure, body mass index (BMI), total cholesterol (TC), triglyceride (TG), FBS and lower high-density lipoprotein cholesterols (HDL-C) levels, compared to those with low levels. Multiple logistic regression analysis revealed that high levels of BMI (OR 1.17, 95% CI 1.01-1.34, P trend = 0.01), TG (OR 1.27, 95% CI 1.07-1.51, P trend = 0.006), and FBS (OR 1.19 95% CI 1.01-1.40, P trend = 0.05) were significantly associated with prevalence of colorectal adenoma. Subjects with high levels of BMI, TG and FBS have increased prevalence of developing colorectal adenoma in Korea.

Pyo, Jeung Hui; Chun, Hoon Jai; Keum, Bora; Jeen, Yoon Tae; Lee, Hong Sik; Kim, Chang Duck; Ryu, Ho Sang; Kim, Young Ha; Lee, Jung Eun

2013-01-01

241

Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population.  

PubMed

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL?C) and total cholesterol (TC) to HDL?C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL?C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ? 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL?C ratio, TC/HDL?C ratio and low ABI. Results: The TG/HDL?C ratios for those with ABI > 0.9 and ABI ? 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL?C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL?C ratio and TC/HDL?C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL?C ratio and TC/HDL?C ratio, respectively. Non-linear relationships were detected between TG/HDL?C ratio and TC/HDL?C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL?C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL?C, and LDL-C. TC/HDL?C might be considered as a potential biomarker for early peripheral arterial disease screening. PMID:24797050

Zhan, Yiqiang; Yu, Jinming; Ding, Rongjing; Sun, Yihong; Hu, Dayi

2014-05-01

242

Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of Metabolic Syndrome in HIV patients  

PubMed Central

Introduction Plasma triglycerides (TG) and HDL-C are inversely related in Metabolic Syndrome (MetS), due to exchange of VLDL-TG for HDL-cholesteryl esters catalyzed by cholesteryl ester transfer protein (CETP). We investigated the relationship of TG to HDL-C in highly-active antiretroviral drug (HAART)-treated HIV patients. Methods Fasting plasma TG and HDL-C levels were compared in 179 hypertriglyceridemic HIV/HAART patients and 71 HIV-negative persons (31 normotriglyceridemic (NL) and 40 hypertriglyceridemic due to type IV hyperlipidemia (HTG)). CETP mass and activity were compared in 19 NL and 87 HIV/HAART subjects. Results Among the three groups, a plot of HDL-C vs. TG gave similar slopes but significantly different y-intercepts (9.24 ± 0.45, 8.16 ± 0.54, 6.70 ± 0.65, sqrt(HDL-C) for NL, HIV and HTG respectively; P<0.001); this difference persisted after adjusting HDL-C for TG, age, BMI, gender, glucose, CD4 count, viral load and HAART strata (7.18 ± 0.20, 6.20 ± 0.05 and 4.55 ± 0.15 sqrt(HDL-C) for NL, HIV and HTG, respectively, P <0.001). CETP activity was not different between NL and HIV, but CETP mass was significantly higher in HIV (1.47 ± 0.53 compared to 0.93 ± 0.27 ?g/mL, P<0.0001), hence CETP specific activity was lower in HIV (22.67 ± 13.46 compared to 28.46 ± 8.24 nmol/?g/h, P=0.001). Conclusions Dyslipidemic HIV/HAART patients have a distinctive HDL-C plasma concentration adjusted for TG. The weak inverse relationship between HDL-C and TG is not explained by altered total CETP activity; it could result from a non-CETP-dependent mechanism or a decrease in CETP function due to inhibitors of CETP activity in HIV patients’ plasma.

Vu, Catherine N.; Ruiz-Esponda, Raul; Yang, Eric; Chang, Evelyn; Gillard, Baiba; Pownall, Henry J.; Hoogeveen, Ron C.; Coraza, Ivonne; Balasubramanyam, Ashok

2013-01-01

243

Locked nucleic acid antisense inhibitor targeting apolipoprotein C-III efficiently and preferentially removes triglyceride from large very low-density lipoprotein particles in murine plasma.  

PubMed

A 20-mer phosphorothioate antisense oligodeoxyribonucleotide having locked nucleic acids (LNA-AON) was used to reduce elevated serum triglyceride levels in mice. We repeatedly administered LNA-AON, which targets murine apolipoprotein C-III mRNA, to high-fat-fed C57Bl/6J male mice for 2 weeks. The LNA-AON showed efficient dose-dependent reductions in hepatic apolipoprotein C-III mRNA and decreased serum apolipoprotein C-III protein concentrations, along with efficient dose-dependent reductions in serum triglyceride concentrations and attenuation of fat accumulation in the liver. Through precise lipoprotein profiling analysis of sera, we found that serum reductions in triglyceride and cholesterol levels were largely a result of decreased serum very low-density lipoprotein (VLDL)-triglycerides and -cholesterol. It is noteworthy that larger VLDL particles were more susceptible to removal from blood than smaller particles, resulting in a shift in particle size distribution to smaller diameters. Histopathologically, fatty changes were markedly reduced in antisense-treated mice, while moderate granular degeneration was frequently seen the highest dose of LNA-AON. The observed granular degeneration of hepatocytes may be associated with moderate elevation in the levels of serum transaminases. In conclusion, we developed an LNA-based selective inhibitor of apolipoprotein C-III. Although it remains necessary to eliminate its potential hepatotoxicity, the present LNA-AON will be helpful for further elucidating the molecular biology of apolipoprotein C-III. PMID:24269597

Yamamoto, Tsuyoshi; Obika, Satoshi; Nakatani, Moeka; Yasuhara, Hidenori; Wada, Fumito; Shibata, Eiko; Shibata, Masa-Aki; Harada-Shiba, Mariko

2014-01-15

244

The role of triglyceride lipases in cancer associated cachexia  

PubMed Central

Cancer associated cachexia (CAC) is a complex multiorgan syndrome frequently associated with various forms of cancer. Affected patients suffer from a dramatic loss of skeletal muscle and adipose tissue. Most cases are accompanied by anorexia, and nutritional supplements are not sufficient to stop or reverse its course. CAC impairs many forms of therapeutic interventions and accounts for 15–20% of all deaths of cancer patients. Recently, several studies have recognized the importance of lipid metabolism and triglyceride hydrolysis as a major metabolic pathway involved in the initiation and/or progression of CAC. In this review, we explore the contributions of the triglyceride lipases to CAC and discuss various factors modulating lipase activity.

Das, Suman K.; Hoefler, Gerald

2013-01-01

245

Role of caspase-1 in regulation of triglyceride metabolism  

PubMed Central

Caspase-1 is a cysteine protease that can be activated by both endogenous and exogenous inflammatory stimuli and has been shown to have important functions in processes as diverse as proteolytic activation of cytokines, cell death, and membrane repair. Caspase-1–dependent production of the inflammatory cytokines IL-1 and IL-18 has also been implicated in the regulation of appetite, body weight, glucose homeostasis, and lipid metabolism. Consistent with the emerging views of caspase-1 in metabolic regulation, we find that caspase-1–deficient mice have dramatically accelerated triglyceride clearance, without alteration in lipid production or absorption, and resultant decrease in steady-state circulating triglyceride and fatty acid levels. Surprisingly, this effect is independent of IL-1-family signaling, supporting the concept that caspase-1 influences lipid metabolism through multiple mechanisms, not limited to cytokines.

Kotas, Maya E.; Jurczak, Michael J.; Annicelli, Charles; Gillum, Matthew P.; Cline, Gary W.; Shulman, Gerald I.; Medzhitov, Ruslan

2013-01-01

246

Understanding triglyceride levels related to intravenous fat administration.  

PubMed

Lipid is an essential macronutrient in parenteral nutrition (PN) support. intravenous (IV) lipid provides essential fatty acids and a concentrated calorie source. Preterm infants are at risk for essential fatty deficiency early in life. Lipid administration is associated with some risks, and there are guidelines for administration to minimize complications. Lipid emulsions in the United States are derived from soybean oil. Outside of the United States, lipid emulsions made from fish oil or combinations of fish, soybean, olive, and medium-chain triglycerides (MCTs) are under investigation for improved tolerance, lower plasma lipid levels, and improved fatty acid profiles, all of which are considered beneficial. Triglyceride levels are an important measurement to assess patient tolerance. PMID:24816878

Weaver, Karen

2014-01-01

247

Supercritical carbon dioxide extraction of triglycerides from Aquilaria crassna seeds  

Microsoft Academic Search

This study examines the effects of pressure, temperature and solvent to solid ratio (SSR) on extraction efficiency of triglycerides from powdered Aquilaria crassna seeds by using supercritical carbon dioxide (SC-CO2) extraction. Supercritical extractions were designed for pressures ranging from 250 to 350bar, temperatures ranging from 313 to 333K and SSR values ranging from 60:1 to 120:1. All values were selected

Wei-Heng Chen; Ching-Hung Chen; Chieh-Ming J. Chang; Bing-Chung Liau; Daina Hsiang

2010-01-01

248

Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia  

Microsoft Academic Search

We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid- lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body

Marina Cuchel; LeAnne T. Bloedon; Philippe O. Szapary; Daniel M. Kolansky; Megan L. Wolfe; Antoine Sarkis; John S. Millar; Katsunori Ikewaki; Evan S. Siegelman; Richard E. Gregg; Daniel J. Rader

2007-01-01

249

A method for the structural analysis of triglycerides and lecithins  

Microsoft Academic Search

The structural analysis of lecithins and triglycerides is described. The procedure is carried out on 2–5 mg of sample by a\\u000a combination of reductive ozonolysis and thin-layer chromatography (TLC). The ozonides as well as the aldehyde “cores” derived\\u000a from reduction of the ozonides are separated by TLC and analyzed quantitatively by densitometry. The constituent saturated\\u000a fatty acids of the separated

O. S. Privett; M. L. Blank

1963-01-01

250

Effect of heat on triglycerides of corn oil  

Microsoft Academic Search

Results of a study on the effect of heating corn oil in air to a 200C temp are reported. Heated oil was separated on a silicic\\u000a acid column into 8 fractions. The first four fractions, constituting about 62% original oil, were found to be unchanged triglycerides.\\u000a The remaining 4 fractions constituted polymeric and degraded products of high molecular wt. Percentage

M. R. Sahasrabudhe; I. G. Farn

1964-01-01

251

Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation.  

PubMed

Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apoB transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma insulin levels after 9 and 12 months, respectively, improved intra peritoneal glucose tolerance after 6 months, and a trend towards increased insulin-stimulated glucose uptake in isolated skeletal muscle. Conclusions. The data suggests that overexpression of apoB decreases skeletal muscle lipid accumulation and attenuates peripheral insulin resistance in obese mice. PMID:24673444

Bartels, Emil D; Ploug, Thorkil; Størling, Joachim; Mandrup-Poulsen, Thomas; Nielsen, Lars B

2014-06-01

252

Diffuse-reflectance Fouriertransform infrared spectroscopy of vegetable oil triglyceride adsorption on silicic acid  

Microsoft Academic Search

The adsorption of triglyceride by silicic acid from hexane miscellas was observed with diffuse-reflectance Fouriertransform\\u000a infrared spectroscopy. Triglyceride was adsorbed by hydrogen bonding to silanol groups through the ester carbonyl group. Addition\\u000a of isopropanol (IPA) to the triglyceride-hexane solution prior to adsorption resulted in unchanged triglyceride adsorption\\u000a on silicic acid despite IPA's ability to adsorb on silicic acid and hydrogen-bond

C. Adhikari; A. Proctor; G. D. Blyholder

1994-01-01

253

Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins.  

PubMed

Murine P388D1 macrophages have a receptor pathway that binds human hypertriglyceridemic very low density lipoproteins (HTG-VLDL) that is fundamentally distinct from the LDL receptor pathway. Trypsin-treated HTG-VLDL (tryp-VLDL), devoid of apolipoprotein (apo)-E, fail to bind to the LDL receptor, yet tryp-VLDL and HTG-VLDL cross-compete for binding to P388D1 macrophage receptors, indicating that these lipoproteins bind to the same sites. The specific, high affinity binding of tryp-VLDL and HTG-VLDL to macrophages at 4 degrees C is equivalent and at 37 degrees C both produce rapid, massive, curvilinear (receptor-mediated) triglyceride accumulation in macrophages. Ligand blots show that P388D1 macrophages express a membrane protein of approximately 190 kD (MBP190) that binds both tryp-VLDL and HTG-VLDL; this binding is competed by HTG-VLDL, trypsinized HTG-VLDL, and trypsinized normal VLDL but not by normal VLDL or LDL. The macrophage LDL receptor (approximately 130 kD) and cellular uptake of beta-VLDL, but not MBP 190 nor uptake of tryp-VLDL, are induced when cells are exposed to lipoprotein-deficient medium and decreased when cells are cholesterol loaded. Unlike the macrophage LDL receptor, MBP 190 partitions into the aqueous phase after phase separation of Triton X-114 extracts. An anti-LDL receptor polyclonal antibody blocks binding of HTG-VLDL to the LDL receptor and blocks receptor-mediated uptake of beta-VLDL by P388D1 cells but fails to inhibit specific cellular uptake of tryp-VLDL or to block binding of tryp-VLDL to MBP 190. Human monocytes, but not human fibroblasts, also express a binding protein for HTG-VLDL and tryp-VLDL similar to MBP 190. We conclude that macrophages possess receptors for abnormal human triglyceride-rich lipoproteins that are distinct from LDL receptors in ligand specificity, regulation, immunological characteristics, and cellular distribution. MBP 190 shares these properties and is a likely receptor candidate for the high affinity uptake of TG-rich lipoproteins by macrophages. PMID:3183059

Gianturco, S H; Lin, A H; Hwang, S L; Young, J; Brown, S A; Via, D P; Bradley, W A

1988-11-01

254

Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasidone or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controlled clinical trials.  

PubMed

The objective of this study was to determine if early changes in triglycerides and weight may be useful in predicting longer-term changes in weight and other metabolic parameters. Data were from three 24- to 28-week randomized, controlled studies comparing olanzapine to ziprasidone or aripiprazole for treatment of schizophrenia. Analyses were restricted to completers with fasting laboratory data at all protocol specified time points. Analyses were primarily descriptive and included mean changes and categorical outcomes. In all treatment groups, participants who did not experience a 20 mg/dL or greater increase in triglycerides at early time points were unlikely to experience a change of 50 mg/dL or more in triglycerides after 6 months. Negative predictive values were 83% to 95%. However, early change in triglycerides was not useful for predicting later change in glucose, cholesterol, or weight. Similarly, early weight change gave robust negative predictive values for longer-term weight change (?10 kg), but not for change in glucose or cholesterol. Lack of early elevation in triglyceride concentrations was predictive of later lack of substantial increase in triglycerides in olanzapine-, ziprasidone-, and aripiprazole-treated participants. Lack of early elevation in weight was predictive of later lack of substantial increase in weight in all 3 treatment groups. Early monitoring of triglyceride concentrations and weight may help clinicians assess risk that individuals will experience significant increase in triglycerides or weight gain, allowing assessments of potential risks and benefits earlier in treatment. Clinical monitoring is advised throughout treatment for all patients. PMID:21105275

Hoffmann, Vicki P; Case, Michael; Stauffer, Virginia L; Jacobson, Jennie G; Conley, Robert R

2010-12-01

255

Rapid and sensitive enzymatic-radiochemical assay for the determination of triglycerides  

SciTech Connect

An enzymatic-radiochemical method suitable for the determination of triglyceride levels of cells in culture is described. The method is based on the enzymatic hydrolysis of triglycerides to free fatty acids which then complex with /sup 63/Ni. The method is rapid, accurate, and inexpensive. The procedure extends the sensitivity of triglyceride measurement to as low as 0.25 nanomoles.

Khoo, J.C.; Miller, E.; Goldberg, D.I.

1987-07-01

256

Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase  

Microsoft Academic Search

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial

Robert Zimmermann; Juliane G. Strauss; Guenter Haemmerle; Gabriele Schoiswohl; Ruth Birner-Gruenberger; Monika Riederer; Achim Lass; Georg Neuberger; Frank Eisenhaber; Albin Hermetter; Rudolf Zechner

2004-01-01

257

Elevated Mcl-1 inhibits thymocyte apoptosis and alters thymic selection  

PubMed Central

T cells developing in the thymus undergo rigorous positive and negative selection to ensure that those exported to peripheral lymphoid organs bear T-cell receptors (TCRs) capable of reacting with foreign antigens but tolerant of self. At each checkpoint, whether a thymocyte survives or dies is determined by antiapoptotic and proapoptotic Bcl-2 family members. We used Mcl-1 transgenic (tg) mice to investigate the impact of elevated expression of antiapoptotic Mcl-1 on thymocyte apoptosis and selection, making a side-by-side comparison with thymocytes from BCL-2tg mice. Mcl-1 was as effective as Bcl-2 at protecting thymocytes against spontaneous cell death, diverse cytotoxic insults and TCR–CD3 stimulation-driven apoptosis. In three different TCR tg models, Mcl-1 markedly enhanced positive selection of thymocytes, as did Bcl-2. In H-Y TCR tg mice, elevated Mcl-1 and Bcl-2 were equally effective at inhibiting deletion of autoreactive thymocytes. However, in the OT-1tg model where deletion is mediated by a peripheral antigen whose expression is regulated by Aire, Mcl-1 was less effective than Bcl-2. Thus, the capacity of Mcl-1 overexpression to inhibit apoptosis triggered by TCR stimulation apparently depends on the thymocyte subset subject to deletion, presumably due to differences in the profiles of proapoptotic Bcl-2 family members mediating the deletion.

Campbell, K J; Gray, D H D; Anstee, N; Strasser, A; Cory, S

2012-01-01

258

Endocrine and Metabolic Effects of Consuming Fructose and Glucose Sweetened Beverages with Meals in Obese Men and Women: Influence of Insulin Resistance on Plasma Triglyceride Responses  

Microsoft Academic Search

Context: Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates post- prandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal weight women. The effects of fructose, compared with glucose, ingestion on metabolic profiles in obese subjects has not been studied. Objective: Compare the effects of fructose- and glucose-sweetened beverages consumed with meals on hormones and

Karen L. Teff; Joanne Grudziak; Raymond R. Townsend; Tamara N. Dunn; Ryan W. Grant; Sean H. Adams; Nancy L. Keim; Bethany P. Cummings; Kimber L. Stanhope; Peter J. Havel

2009-01-01

259

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels  

Microsoft Academic Search

Aims\\/hypothesis  Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL\\/remnants and chylomicrons\\/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance.Methods  We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity,

M. T. Pedrini; M. Kranebitter; A. Niederwanger; S. Kaser; J. Engl; P. Debbage; L. A. Huber; J. R. Patsch

2005-01-01

260

A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid-binding protein 2 reduce plasma triglyceride-rich lipoproteins.  

PubMed

The threonine-encoding allele (Thr54) of the fatty acid-binding protein 2 (FABP2) DNA polymorphism is associated with increased triglyceride (TG)-rich lipoproteins (TRL). We hypothesized that the TRL response to diets of varied fat content is affected by the FABP2 A54T polymorphism, specifically that a high-fat diet would reduce TRL and that the Thr54 allele would have an enhanced response. Sixteen healthy, postmenopausal women completed a crossover dietary intervention that included three 8-week, isoenergetic diet treatments. The treatments consisted of high fat (40% of energy as fat), low fat (20% of energy), and low fat + n-3 fatty acids (20% of energy plus 3% as n-3 fatty acids). Eight subjects were homozygous for the wild type (Ala54/Ala54) of the FABP2 polymorphism, whereas 8 subjects had at least 1 Thr54 allele (7, Ala54/Thr54; 1, Thr54/Thr54). High-fat diet showed significantly reduced plasma TGs, chylomicron TG, and very low-density lipoprotein TG from baseline in all participants. Although carriers of the Thr54 allele of the FABP2 polymorphism had significantly reduced TRL, there is no evidence of an interaction, which does not support our hypothesis. The alanine-encoding allele did not influence the dietary effects on the plasma lipids. PMID:21840466

McColley, Steven P; Georgopoulos, Angeliki; Young, Lindsay R; Kurzer, Mindy S; Redmon, J Bruce; Raatz, Susan K

2011-07-01

261

Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome.  

PubMed

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation. PMID:15015142

Tremblay, André J; Després, Jean-Pierre; Piché, Marie-Eve; Nadeau, André; Bergeron, Jean; Alméras, Natalie; Tremblay, Angelo; Lemieux, Simone

2004-03-01

262

Omega3 fatty acid supplementation accelerates chylomicron triglyceride clearance  

Microsoft Academic Search

Omega-3 fatty acids (FAs) reduce postprandial triacylglycerol (TG) concentrations. This study was under- taken to determine whether this effect was due to reduced production or increased clearance of chylomicrons. Healthy subjects (n ? 33) began with a 4-week, olive oil placebo (4 g\\/d) run-in period. After a 4-week wash-out period, subjects were randomized to supplementation with 4 g\\/d of ethyl

Yongsoon Park; William S. Harris

2003-01-01

263

ApoC-III and visceral adipose tissue contribute to paradoxically normal triglyceride levels in insulin-resistant African-American women  

PubMed Central

Background African-Americans are more insulin-resistant than whites but have lower triglyceride (TG) concentrations. The metabolic basis for this is unknown. Our goal was to determine in a cross-sectional study the effect of insulin resistance, visceral adipose tissue (VAT) and the apolipoproteins, B, C-III and E, on race differences in TG content of very low density lipoproteins (VLDL). Methods The participants were 31 women (16 African-American, 15 white) of similar age (37?±?9 vs. 38?±?11y (mean?±?SD), P =?0.72) and BMI (32.4?±?7.2 vs. 29.3?±?6.0 kg/m2, P =?0.21). A standard diet (33% fat, 52% carbohydrate, 15% protein) was given for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. VAT was measured at L2-3. The influence of race, SI, VAT and apolipoproteins on the TG content of VLDL was determined by random effects models (REM). Results African-Americans were more insulin-resistant (SI: 3.6?±?1.3 vs. 5.6?±?2.6 mU/L-1.min-1, P TG, apoB and apoC-III content of light and dense VLDL were lower in African-Americans (all P TG concentration of VLDL. In models with race, SI, VAT and all apolipoproteins entered, race was not significant but apoC-III and VAT remained significant determinants of TG concentration in light and dense VLDL. Conclusions Low concentrations of apoC-III and VAT in African-Americans contribute to race differences in TG concentrations. Trial registration ClinicalTrials.gov Identifier: NCT00484861

2013-01-01

264

Characterization of Anopheles gambiae transglutaminase 3 (AgTG3) and its native substrate Plugin.  

PubMed

Male Anopheles mosquitoes coagulate their seminal fluids via cross-linking of a substrate, called Plugin, by the seminal transglutaminase AgTG3. Formation of the "mating plug" by cross-linking Plugin is necessary for efficient sperm storage by females. AgTG3 has a similar degree of sequence identity (~30%) to both human Factor XIII (FXIII) and tissue transglutaminase 2 (hTG2). Here we report the solution structure and in vitro activity for the cross-linking reaction of AgTG3 and Plugin. AgTG3 is a dimer in solution and exhibits Ca(2+)-dependent nonproteolytic activation analogous to cytoplasmic FXIII. The C-terminal domain of Plugin is predominantly ?-helical with extended tertiary structure and oligomerizes in solution. The specific activity of AgTG3 was measured as 4.25 × 10(-2) units mg(-1). AgTG3 is less active than hTG2 assayed using the general substrate TVQQEL but has 8-10× higher relative activity when Plugin is the substrate. Mass spectrometric analysis of cross-linked Plugin detects specific peptides including a predicted consensus motif for cross-linking by AgTG3. These results support the development of AgTG3 inhibitors as specific and effective chemosterilants for A. gambiae. PMID:23288850

Le, Binh V; Nguyen, Jennifer B; Logarajah, Shankar; Wang, Bo; Marcus, Jacob; Williams, Hazel P; Catteruccia, Flaminia; Baxter, Richard H G

2013-02-15

265

Making the Tg-Confinement Effect Disappear in Thin Polystyrene Films: Good Physics vs. Inappropriate Analysis  

NASA Astrophysics Data System (ADS)

The Tg-confinement effect in polymers was first characterized in supported polystyrene (PS) films by Keddie et al. in 1994. Since then, many researchers have shown that (pseudo-)thermodynamic Tg measurements of supported PS films taken on cooling consistently yield the same qualitative results, with a decrease from bulk Tg beginning at 40-60 nm thickness and becoming very strong below 20 nm thickness. Some quantitative differences have been noted between studies, which may be ascribed to measurement method or the analysis employed. In 2004, we showed that the Tg-confinement effect in PS may be suppressed by adding several wt% of small-molecule diluents such as dioctyl phthalate. Recently, Kremer and co-workers (Macromolecules 2010, 43, 9937) reported that there was no Tg-confinement in supported PS films based on an analysis of the second derivative of ellipsometry data and use of a ninth order polynomial fit. Here, we demonstrate a new method for suppressing the Tg-confinement effect. In particular, PS made by emulsion polymerization yields no Tg-confinement effect as measured by ellipsometry or fluorescence, while PS made by anionic or conventional free radical polymerization yield strong Tg-confinement effects. The difference is hypothesized to result from surfactant in the emulsion polymerized PS. We also show that the absence of the Tg-confinement effect reported by Kremer is due to inappropriate analysis of ellipsometry data and that correct analysis yields Tg-confinement effects.

Torkelson, John; Chen, Lawrence

2013-03-01

266

Characterization of Anopheles gambiae Transglutaminase 3 (AgTG3) and Its Native Substrate Plugin*  

PubMed Central

Male Anopheles mosquitoes coagulate their seminal fluids via cross-linking of a substrate, called Plugin, by the seminal transglutaminase AgTG3. Formation of the “mating plug” by cross-linking Plugin is necessary for efficient sperm storage by females. AgTG3 has a similar degree of sequence identity (?30%) to both human Factor XIII (FXIII) and tissue transglutaminase 2 (hTG2). Here we report the solution structure and in vitro activity for the cross-linking reaction of AgTG3 and Plugin. AgTG3 is a dimer in solution and exhibits Ca2+-dependent nonproteolytic activation analogous to cytoplasmic FXIII. The C-terminal domain of Plugin is predominantly ?-helical with extended tertiary structure and oligomerizes in solution. The specific activity of AgTG3 was measured as 4.25 × 10?2 units mg?1. AgTG3 is less active than hTG2 assayed using the general substrate TVQQEL but has 8–10× higher relative activity when Plugin is the substrate. Mass spectrometric analysis of cross-linked Plugin detects specific peptides including a predicted consensus motif for cross-linking by AgTG3. These results support the development of AgTG3 inhibitors as specific and effective chemosterilants for A. gambiae.

Le, Binh V.; Nguyen, Jennifer B.; Logarajah, Shankar; Wang, Bo; Marcus, Jacob; Williams, Hazel P.; Catteruccia, Flaminia; Baxter, Richard H. G.

2013-01-01

267

A reversible early oxidized redox state that precedes macromolecular ROS damage in aging non-transgenic and 3xTg-AD mouse neurons  

PubMed Central

The brain depends on redox electrons from NADH to produce ATP and oxyradicals (ROS). Since ROS damage and mitochondrial dysregulation are prominent in aging and Alzheimer’s disease (AD) and their relationship to redox state is unclear, we wanted to know whether an oxidative redox shift precedes these markers and leads to macromolecular damage in a mouse model of AD. We used the 3xTg-AD mouse model that displays cognitive deficits beginning at 4 months. Hippocampal/cortical neurons were isolated across the age-span and cultured in common nutrients to control for possible hormonal and vascular differences. We found an increase of NAD(P)H levels and redox state in non-transgenic neurons until middle age, followed by a decline in old age. The 3xTg-AD neurons maintained much lower resting NAD(P)H and redox state after 4 months, but the NADH regenerating capacity continuously declined with age beginning at 2 months. These redox characteristics were partially reversible with nicotinamide, a biosynthetic precursor of NAD+. Nicotinamide also protected against glutamate excitotoxicity. Compared to non-transgenic neurons, 3xTg-AD neurons possessed more mitochondria/neuron and lower glutathione levels which preceeded age-related increases in ROS levels. These glutathione deficits were again reversible with nicotinamide in 3xTg-AD neurons. Surprisingly, low macromolecular ROS damage was only elevated after 4 months in the 3xTg-AD neurons if anti-oxidants were removed. The present data suggest that a more oxidized redox state and a lower antioxidant glutathione defense can be dissociated from neuronal ROS damage, changes that precede the onset of cognitive deficits in the 3xTg-AD model.

Ghosh, D.; LeVault, K.; Barnett, A.; Brewer, G.J.

2012-01-01

268

A Report of High Triglyceride Level in Cord Blood of Iranian Newborns  

PubMed Central

Background: Since cord blood triglyceride level have been reported very different in recent articles, the purpose of this study is determination of triglyceride level in cord blood of Iranian newborns and compare it with other reports. Methods: In this study, cord blood of 174 healthy term newborn infants (97 girls, 77 boys) born from healthy mothers have been used. Triglyceride level has been measured by calorie metric method Statistical analysis was performed by independent t test, Mann-Whitney regression test and Spearman correlation coefficient method using SPSS 16 .0 software (SPSS, USA). Results: The mean of cord blood triglyceride was 1.37 ± 4.81 mg /dl and there was no statistical difference between two sexes. There was not exist linear relationship between triglyceride and weight, height, head circumference, body mass index and sex of the babies. In 8.6% of our new born infants, triglyceride levels were more than 95th percentile of triglyceride level reported in Iranian population. In 33.9% of our cases, triglyceride levels were more than 95th percentile of triglyceride level reported in the Nelson text book of Pediatrics. In this study, the 95th percentile of triglyceride level in cord blood was 132.5 mg /dl. Conclusion: The mean and 95th percentiles of triglyceride levels in cord blood of our newborn infants were higher than other reports. We recommend that larger studies should be conducted in this area to establish preventive ways for increasing epidemic of the metabolic syndrome.

Kazemi, Seyed Ali Naghi; Mousavinasab, Nooreddin; Mellati, Ali Awsat; Sadeghzadeh, Mansour

2013-01-01

269

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study  

PubMed Central

Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ? 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-?4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ?4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

2010-01-01

270

Oral zinc reduces amyloid burden in Tg2576 mice  

PubMed Central

The aggregation of amyloid beta in Alzheimer’s disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid beta in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid beta in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid beta aggregation.

Harris, Christopher J.; Voss, Kellen; Murchison, Charles; Ralle, Martina; Frahler, Kate; Carter, Raina; Rhoads, Alison; Lind, Betty; Robinson, Emily; Quinn, Joseph F.

2014-01-01

271

William T.G. Morton and "The Great Moment".  

PubMed

The Great Moment, a Paramount movie released in 1944 about dentist William T.G. Morton's discovery of ether anesthesia a century earlier, was the odd-man-out among the movies made by the highly acclaimed director Preston Sturges in that period. It failed to attract large audiences and generally received only lukewarm reviews. Several biographies of Sturges have discussed the reasons for this anomaly; but only recently have drafts of the various versions of Sturges' scripts been published, plus additional background material about the film's production, revisions and editing. Using all this information, the author analyzes the movie and its history and asks what went wrong - and, more importantly, what went right. The general conclusion is that this little-known film has stood the test of time and is worthy of a revival among enthusiasts of dental history and a serious reassessment by movie critics in general. Despite some flaws in the final version, The Great Moment is in fact a remarkable medical biography, incorporating innovative flashback techniques and themes of inspiration and sacrifice mixed with some humor, while remaining reasonably true to historical facts surrounding dentistry's greatest triumph. PMID:12641171

Heynick, Frank

2003-03-01

272

TG-69: Radiographic film for megavoltage beam dosimetry  

SciTech Connect

TG-69 is a task group report of the AAPM on the use of radiographic film for dosimetry. Radiographic films have been used for radiation dosimetry since the discovery of x-rays and have become an integral part of dose verification for both routine quality assurance and for complex treatments such as soft wedges (dynamic and virtual), intensity modulated radiation therapy (IMRT), image guided radiation therapy (IGRT), and small field dosimetry like stereotactic radiosurgery. Film is convenient to use, spatially accurate, and provides a permanent record of the integrated two dimensional dose distributions. However, there are several challenges to obtaining high quality dosimetric results with film, namely, the dependence of optical density on photon energy, field size, depth, film batch sensitivity differences, film orientation, processing conditions, and scanner performance. Prior to the clinical implementation of a film dosimetry program, the film, processor, and scanner need to be tested to characterize them with respect to these variables. Also, the physicist must understand the basic characteristics of all components of film dosimetry systems. The primary mission of this task group report is to provide guidelines for film selection, irradiation, processing, scanning, and interpretation to allow the physicist to accurately and precisely measure dose with film. Additionally, we present the basic principles and characteristics of film, processors, and scanners. Procedural recommendations are made for each of the steps required for film dosimetry and guidance is given regarding expected levels of accuracy. Finally, some clinical applications of film dosimetry are discussed.

Pai, Sujatha; Das, Indra J.; Dempsey, James F.; Lam, Kwok L.; LoSasso, Thomas J.; Olch, Arthur J.; Palta, Jatinder R.; Reinstein, Lawrence E.; Ritt, Dan; Wilcox, Ellen E. [Radiation Therapy Department, Memorial Hermann Hospital, Houston, Texas 77024 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610 (United States); Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109 (United States); Medical Physics Department, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 (United States); Radiation Oncology Program, Childrens Hospital of LA, Los Angeles, California 90027 (United States); Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610 (United States); Radiation Oncology Department, SUNY Stony Brook University Hospital, Stony Brook, New York 11794 (United States); Radiological Imaging Technology, Inc., Colorado Springs, Colorado 80907 (United States); Radiation Oncology Department, St. Francis Hospital, Hartford, Connecticut 06105 (United States)

2007-06-15

273

Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex  

PubMed Central

Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer’s disease (AD). Whether and how brain/neuronal activity might modulate certain pathological process of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris-occlusion caused BACE1 elevation in neuronal terminals in the deprived relative to the non-deprived bulb and piriform cortex in young adult mice. In parallel with the overall age-related plaque development in the forebrain, locally-increased BACE1 immunoreactivity co-occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non-deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non-deprived bulbs. Plaque-associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with A? immunoreactivity occurred inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology.

Zhang, Xue-Mei; Xiong, Kun; Cai, Yan; Cai, Huaibin; Luo, Xue-Gang; Feng, Jia-Chun; Clough, Richard W.; Patrylo, Peter R.; Struble, Robert G.; Yan, Xiao-Xin

2010-01-01

274

Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members.  

PubMed

Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on the presence of the active site serine for Adiponutrin, Desnutrin/ATGL, and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like, but not Adiponutrin, decreases intracellular triglyceride levels. This is consistent with a function for Desnutrin/ATGL, GS2, and GS2-Like in lipolysis, but not for Adiponutrin. Consistent with previously reported data, Desnutrin/ATGL is upregulated by fasting in adipose tissue, whereas Adiponutrin is downregulated. Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL, are strongly induced in the liver of ob/ob mice. Our data support distinct functions for Adiponutrin and Desnutrin/ATGL and raise the possibility that GS2 may contribute significantly to lipolysis in human adipose tissue. PMID:16150821

Lake, Andrew C; Sun, Ying; Li, Jian-Liang; Kim, Jae Eun; Johnson, Jeremy W; Li, Dongmei; Revett, Tracy; Shih, Heather H; Liu, Wei; Paulsen, Janet E; Gimeno, Ruth E

2005-11-01

275

Contribution of High Plasma Triglycerides and Low High-Density Lipoprotein Cholesterol to Residual Risk of Coronary Heart Disease After Establishment of Low-Density Lipoprotein Cholesterol Control  

PubMed Central

To determine the relative contributions of triglycerides (TGs) and high-density lipoprotein (HDL) cholesterol in the residual risk of coronary heart disease (CHD) after the reduction of low-density lipoprotein (LDL) cholesterol to guideline-recommended levels, we conducted a hospital-based, case-control study with optimal matching in the strata of LDL cholesterol, gender, ethnicity, and age. The 170 cases and 175 controls were patients at Brigham and Women's Hospital (Boston, Massachusetts) from 2005 to 2008 who had an LDL cholesterol level <130 mg/dl. The cases had incident CHD, and the controls had diagnoses unrelated to CHD. The 170 cases and 175 controls had a mean LDL cholesterol level of 73 and 87 mg/dl, respectively. The association between TG and HDL cholesterol levels and CHD risk was assessed using conditional and unconditional logistic regression analysis. The models investigated accommodated the possibility of an interaction between lipid factors. The odds of CHD increased by approximately 20% per 23-mg/dl increase in TGs and decreased by approximately 40% per 7.5-mg/dl decrease in HDL cholesterol. High TGs and low HDL cholesterol interacted synergistically to increase the odds ratio to 10 for the combined greatest TG (?190 mg/dl) and lowest HDL cholesterol quintiles (<30 mg/dl). High TG levels were more strongly associated with CHD when the HDL cholesterol was low than average or high; and low HDL cholesterol levels were more strongly associated with CHD when the TGs were high. TGs and HDL cholesterol were associated with CHD in patients with a LDL cholesterol level of ?70 mg/dl, with a risk similar to, or greater than, those in the total group. In conclusion, high TG and low HDL cholesterol levels contribute strongly and synergistically to CHD when LDL cholesterol is well controlled. Thus, high TGs might have greater importance in patients with optimal rather than greater LDL cholesterol concentrations.

Carey, Vincent J.; Bishop, Louise; Laranjo, Nancy; Harshfield, Benjamin J.; Kwiat, Carolyn; Sacks, Frank M.

2014-01-01

276

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.  

PubMed

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (? 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L; Descamps, Olivier S; Fisher, Edward; Kovanen, Petri T; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G; Ray, Kausik K; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F

2011-06-01

277

The Role of TG2 in Regulating S100A4-Mediated Mammary Tumour Cell Migration  

PubMed Central

The importance of S100A4, a Ca2+-binding protein, in mediating tumour cell migration, both intracellularly and extracellularly, is well documented. Tissue transglutaminase (TG2) a Ca2+-dependent protein crosslinking enzyme, has also been shown to enhance cell migration. Here by using the well characterised non-metastatic rat mammary R37 cells (transfected with empty vector) and highly metastatic KP1 cells (R37 cells transfected with S100A4), we demonstrate that inhibition of TG2 either by TG2 inhibitors or transfection of cells with TG2 shRNA block S100A4-accelerated cell migration in the KP1cells and in R37 cells treated with exogenous S100A4. Cell migration was also blocked by the treatment with the non-cell permeabilizing TG2 inhibitor R294, in the human breast cancer cell line MDA-MB-231 (Clone 16, which has a high level of TG2 expression). Inhibition was paralleled by a decrease in S100A4 polymer formation. In vitro co-immunoprecipitation and Far Western blotting assays and cross-linking assays showed not only the direct interaction between TG2 and S100A4, but also confirmed S100A4 as a substrate for TG2. Using specific functional blocking antibodies, a targeting peptide and a recombinant protein as a competitive treatment, we revealed the involvement of syndecan-4 and ?5?1 integrin co-signalling pathways linked by activation of PKC? in this TG2 and S100A4-mediated cell migration. We propose a mechanism for TG2-regulated S100A4-related mediated cell migration, which is dependent on TG2 crosslinking.

Wang, Zhuo; Griffin, Martin

2013-01-01

278

Measurement of Myocardial Fatty Acid Esterification Using [1-11C]Palmitate and PET: Comparison with Direct Measurements of Myocardial Triglyceride Synthesis  

PubMed Central

The purpose of the present study was to assess the accuracy of non-invasive estimates of the rate of myocardial fatty acid esterification (MFAE) obtained using positron emission tomography (PET). Methods Sixteen dogs were studied after an overnight fast (FAST), during a euglycemic hyperinsulinemic clamp (CLAMP), or during infusion of Intralipid (IL) or IL plus dobutamine (IL/DOB) (n=4/group). The rate of MFAE was quantified using a bolus injection of [1-11C]palmitate and compartmental modeling as described by Bergmann et al.3 and compared to the rate of triglyceride (TG) synthesis measured directly using a continuous infusion of [1-13C]palmitate and tissue sampling. Results Across groups, mean plasma free fatty acid (FFA) concentration varied ~20-fold, with this variation in FFA availability accompanied by a ~20-fold range in directly-measured TG synthesis (i.e., from 7±1 nmol/min/g in CLAMP to 128±75 nmol/min/g in IL). PET-based estimates of MFAE varied to a similar degree (i.e., from 22±9 nmol/min/g in CLAMP to 543±551 nmol/min/g in IL), and were significantly correlated with TG synthesis (i.e., R=0.77, P<0.001). MFAE, however, was 3- to 4-fold higher than TG synthesis in FAST, CLAMP, and IL, but comparable when cardiac work was increased in IL/DOB, suggesting that MFAE reflects, in part, the incorporation of label into amino acids via TCA cycle exchange reactions (e.g., ?-ketoglutarate ? glutamate) as well as the synthesis of TG and other lipids. Conclusions Changes in the rate of MFAE as determined using PET and the compartmental model of Bergmann et al.3 parallel changes in the rate of TG synthesis, at least in the basal state. Although such measurements are not as robust as rates of myocardial FFA uptake and oxidation as estimated by the model, this method should still be useful for quantifying acute changes in FFA storage by the heart in various pathophysiological states.

Coggan, Andrew R.; Kisrieva-Ware, Zulfia; Dence, Carmen S.; Eisenbeis, Paul; Gropler, Robert J.; Herrero, Pilar

2010-01-01

279

Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides.  

PubMed

Circadian clocks play a major role in orchestrating daily physiology, and their disruption can evoke metabolic diseases such as fatty liver and obesity. To study the role of circadian clocks in lipid homeostasis, we performed an extensive lipidomic analysis of liver tissues from wild-type and clock-disrupted mice either fed ad libitum or night fed. To our surprise, a similar fraction of lipids (?17%) oscillated in both mouse strains, most notably triglycerides, but with completely different phases. Moreover, several master lipid regulators (e.g., PPAR?) and enzymes involved in triglyceride metabolism retained their circadian expression in clock-disrupted mice. Nighttime restricted feeding shifted the phase of triglyceride accumulation and resulted in ?50% decrease in hepatic triglyceride levels in wild-type mice. Our findings suggest that circadian clocks and feeding time dictate the phase and levels of hepatic triglyceride accumulation; however, oscillations in triglycerides can persist in the absence of a functional clock. PMID:24506873

Adamovich, Yaarit; Rousso-Noori, Liat; Zwighaft, Ziv; Neufeld-Cohen, Adi; Golik, Marina; Kraut-Cohen, Judith; Wang, Miao; Han, Xianlin; Asher, Gad

2014-02-01

280

Study on pyrolysis of typical medical waste materials by using TG-FTIR analysis  

Microsoft Academic Search

Pyrolysis of certain medical waste materials was studied using thermogravimetric analyzer coupled with Fourier transform infrared spectroscopy (TG-FTIR). Pyrolysis characteristics of three common materials were discussed. The pyrolysis of absorbent cotton turned out to be the most concentrative, followed by medical respirator and bamboo stick. From TG and DTG curves, pyrolysis of these three materials occurred in single, two and

H. M. Zhu; J. H. Yan; X. G. Jiang; Y. E. Lai; K. F. Cen

2008-01-01

281

TgVTC2 is Involved in Polyphosphate Accumulation in Toxoplasma gondii  

PubMed Central

Polyphosphate is found in every cell, having roles in diverse processes, including differentiation and response to stress. In this study, we characterize a Toxoplasma gondii mutant containing an insertion within the carboxy-terminal end of a homolog of Saccharomyces cerevisiae Vtc2p, a component of the polyphosphate synthetic machinery. Locus TgVTC2 encodes a 140 kDa protein containing conserved SPX, VTC and transmembrane domains. TgVTC2 localizes in punctate spots within the cytoplasm that do not co-localize with known markers. The TgVTC2 mutant showed dramatically reduced polyphosphate accumulation, a defect restored by introduction of TgVTC2 to the mutant. Insertion within TgVTC2 resulted in increased transcript levels for two loci, including a putative FIKK kinase. These transcript levels were restored to wild-type levels upon complementation with the TgVTC2 locus. The TgVTC2 locus was refractory to knockout, and may be essential. Analysis of this TgVTC2 mutant will facilitate dissection of the T. gondii polyphosphate synthesis pathway.

Rooney, Peggy J.; Ayong, Lawrence; Tobin, Crystal M.; Moreno, Silvia N.J.; Knoll, Laura J.

2011-01-01

282

The role of TG2 in ECV304-related vasculogenic mimicry.  

PubMed

Tumour vasculogenesis can occur by a process referred to as vasculogenic mimicry, whereby the vascular structures are derived from the tumour itself. These tumours are highly aggressive and do not respond well to anti-angiogenic therapy. Here, we use the well characterised ECV304 cell line, now known as the bladder cancer epithelial cell line T24/83 which shows both epithelial and endothelial characteristics, as a model of in vitro vasculogenic mimicry. Using optimised ratios of co-cultures of ECV304 and C378 human fibroblasts, tubular structures were identifiable after 8 days. The tubular structures showed high levels of TG2 antigen and TG in situ activity. Tubular structures and in situ activity could be blocked either by site-directed irreversible inhibitors of TG2 or by silencing the ECV304 TG2 by antisense transfection. In situ activity for TG2 showed co-localisation with both fibronectin and collagen IV. Deposition of these proteins into the extracellular matrix could be reduced by inclusion of non-cell penetrating TG inhibitors when analysed by Western blotting suggesting that the contribution of TG2 to tube formation is extracellular. Incubation of ECV304 cells with these same irreversible inhibitors reduced cell migration which paralleled a loss in focal adhesion assembly, actin cytoskeleton formation and fibronectin deposition. TG2 appears essential for ECV304 tube formation, thus representing a potential novel therapeutic target in the inhibition of vasculogenic mimicry. PMID:22231926

Jones, Richard A; Wang, Zhuo; Dookie, Shakthi; Griffin, Martin

2013-01-01

283

Extending the applicability of TG measurements to industry and to quality ensuring by dimensionless analysis  

Microsoft Academic Search

TheIi=Ei\\/RTi dimensionless evaluation is very suitable for describing the TG measurements according to theEi\\/RTi=lnA +n[ln(1??)i]?ln(d?\\/dr)i equation. TheIi andEi functions make the comparison of the different TG measurements possible quantitatively in the case of more DTG peaks as well.

Z. Adonyi

1996-01-01

284

Differential scanning calorimetry of single acid triglycerides: Effect of chain length and unsaturation  

Microsoft Academic Search

The polymorphism of 13 single acid triglycerides with acyl group chain lengths ranging from 16–22 was studied by differential\\u000a scanning calorimetry. In contrast to the single??-form generally attributed to such triglycerides, at least two intermediate endotherms were found for most samples between\\u000a the least stable (?) and most stable (?) polymorphs. For saturated triglycerides, two versions of the familiar “tuning

J. W. Hagemann; W. H. Tallent; K. E. Kolb

1972-01-01

285

The role of X-ray diffraction in studies of the crystallography of monoacid saturated triglycerides  

Microsoft Academic Search

The contribution that x-ray diffraction has made to the understanding of triglyceride polymorphism is reviewed. The crystal\\u000a structure of these compounds is explained in terms of molecular orientation in the crystal lattices. At the present time only\\u000a the crystal structure of the monoacid saturated triglycerides has been reasonably well defined. Mixed triglycerides and mixtures\\u000a thereof have not yet been fully

C. W. Hoerr; F. R. Paulicka

1968-01-01

286

Quantitation of estolide triglycerides in sapium seeds by high performance liquid chromatography with infrared detection  

Microsoft Academic Search

The kernel oil of Chinese tallow(Sapium sebiferum) seed contains tetraester triglycerides composed oftrans-2, cis-4-decadienoic acid joined in an estolide linkage to 8-hydroxy-5, 6-octadienoic acid. A rapid (< 10 min) method of\\u000a separation and quantitation of the tri-glyceride and estolide triglyceride fractions of the oil has been devel-oped using\\u000a high performance liquid chromatography with infrared detection.

Kathleen Payne-Wahl; Robert Kleiman

1983-01-01

287

Novel Gradient Copolymers Yielding an Unusual Glass Transition Temperature (Tg) Depression  

NASA Astrophysics Data System (ADS)

Gradient copolymers form a novel class of polymer intermediate between random copolymers and block copolymers that cannot be made by conventional free radical or anionic polymerization methods. Nitroxide-mediated controlled radical polymerization has been used to synthesize styrene-acetoxystyrene gradient copolymers of narrow polydispersity with molecular weights up to 80,000 with compositions varying from 80 mol75 mol polystyrene and polyacetoxystyrene made via NMP-CRP exhibit Tg's of 373K and 390K, respectively. Block copolymers yield two Tg's consistent with the homopolymers. In contrast, the gradient copolymers yield Tg's as low as 323K, indicating a depression in Tg of greater than 50K relative to homopolymers. The physical origin of this dramatic depression of Tg will be discussed, and comparisons will be made to other gradient copolymer systems, both single phase and two phase.

Gray, Maisha; Torkelson, John

2003-03-01

288

Bile acid-mediated control of liver triglycerides.  

PubMed

Bile acids (BAs) are steroidal molecules generated in the liver by cholesterol oxidation. Beside their well-established role in lipid absorption and cholesterol homeostasis, they function as signaling molecules and activate dedicated BA receptors such as the farnesoid X receptor (FXR) and the G-protein coupled receptor TGR5. Through activation of downstream signaling pathways of these key receptors, BAs regulate not only their own synthesis and enterohepatic circulation, but also impact on hepatic lipid, glucose, and energy homeostasis. Therefore, BA-regulated signaling pathways have emerged as attractive targets for understanding the regulation of hepatic triglyceride metabolism in health and disease and treating fatty liver disease and associated metabolic disorders. PMID:24222091

Fuchs, Claudia; Claudel, Thierry; Trauner, Michael

2013-11-01

289

Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance  

PubMed Central

OBJECTIVE Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.

Amati, Francesca; Dube, John J.; Alvarez-Carnero, Elvis; Edreira, Martin M.; Chomentowski, Peter; Coen, Paul M.; Switzer, Galen E.; Bickel, Perry E.; Stefanovic-Racic, Maja; Toledo, Frederico G.S.; Goodpaster, Bret H.

2011-01-01

290

Bioconversion of Xylan to triglycerides by oil-rich yeasts. [Cryptococcus albidus; Cryptococcus terricoluus; Trichosporon  

SciTech Connect

A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Crytococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Crytococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase. 22 references.

Fall, R.; Phelps, P.; Spindler, D.

1984-05-01

291

Fracture Simulation of Highly Crosslinked Polymer Networks: Triglyceride-Based Adhesives  

NASA Astrophysics Data System (ADS)

The ACRES program at the U. of Delaware has shown that triglyceride oils derived from plants are a favorable alternative to the traditional adhesives. The triglyceride networks are formed from an initial mixture of styrene monomers, free-radical initiators and triglycerides. We have performed simulations to study the effect of physical composition and physical characteristics of the triglyceride network on the strength of triglyceride network. A coarse-grained, bead-spring model of the triglyceride system is used. The average triglyceride consists of 6 beads per chain, the styrenes are represented as a single bead and the initiators are two bead chains. The polymer network is formed using an off-lattice 3D Monte Carlo simulation, in which the initiators activate the styrene and triglyceride reactive sites and then bonds are randomly formed between the styrene and active triglyceride monomers producing a highly crosslinked polymer network. Molecular dynamics simulations of the network under tensile and shear strains were performed to determine the strength as a function of the network composition. The relationship between the network structure and its strength will also be discussed.

Lorenz, Christian; Stevens, Mark; Wool, Richard

2003-03-01

292

Increased plasma triglycerides, cholesterol and apolipoprotein E during prolonged fasting in normal subjects.  

PubMed Central

Plasma lipid and high density lipoprotein (HDL) levels were studied in 20 normal, healthy, non-obese males while fasting (150 kcal/d with free intake of water) for 6 d in a hunger strike. Plasma triglyceride and cholesterol levels were increased by 18% after 6 d of fasting. HDL-cholesterol concentration was not significantly changed for 4 d, but decreased by 22% after 6 d. Platelet aggregation induced by adenosine diphosphate (ADP) or collagen after 6 d of fasting was in the normal range. In 3 subjects fasted for 9 d, a complete plasma lipoprotein analysis was done. Very low and low density lipoprotein (VLDL and LDL) levels were elevated, whereas HDL was reduced after 9 d of fasting. On isoelectric focusing analysis, a marked reduction in apolipoprotein (apo) E concentration in both VLDL and HDL was noted. Liver function tests showed a reduction in hepatic enzyme activity; and since apo E is of hepatic origin also, we suggest that long fasting inhibits liver function in normal subjects. Images Figure 2

Markel, A.; Brook, J. G.; Aviram, M.

1985-01-01

293

TRIGLYCERIDE, NEFA, AND PREDIABETIC NEUROPATHY: ROLE FOR OXIDATIVE-NITROSATIVE STRESS  

PubMed Central

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome, prior to overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased NEFA, and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. 16 wk-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA, displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mgkg?1d?1, 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit, changes in behavioral measures of sensory function, and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find use in management of this condition.

Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; G.Obrosova, Irina

2012-01-01

294

Elevated Remnant-Like Particle Cholesterol Concentration A Characteristic Feature of the Atherogenic Lipoprotein Phenotype  

Microsoft Academic Search

atients at increased risk of coronary artery disease (CAD) frequently exhibit an atherogenic lipoprotein phenotype characterized by elevated plasma levels of both triglyceride- rich lipoproteins (TRL) and small, dense LDL and low concentrations of HDL cholesterol. Recently, in a large observational study, the calculated non-HDL plasma choles- terol concentration (the sum of the cholesterol contents of LDL, intermediate-density lipoprotein (IDL),

T. B. Twickler; G. M. Dallinga-Thie; J. S. Cohn; M. J. Chapman

2010-01-01

295

High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels  

PubMed Central

High-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Some studies have shown that short-term access to HFCS can cause increased body weight, but the findings are mixed. The current study examined both short- and long-term effects of HFCS on body weight, body fat, and circulating triglycerides. In Experiment 1, male Sprague-Dawley rats were maintained for short term (8 wks) on (1) 12-h/day of 8% HFCS, (2) 12-h/day 10% sucrose, (3) 24-h/day HFCS, all with ad libitum rodent chow, or (4) ad libitum chow alone. Rats with 12-h access to HFCS gained significantly more body weight than animals given equal access to 10% sucrose, even though they consumed the same number of total calories but fewer calories from HFCS than sucrose. In Experiment 2, the long-term effects of HFCS on body weight and obesogenic parameters, as well as gender differences, were explored. Over the course of 6 or 7 months, both male and female rats with access to HFCS gained significantly more body weight than control groups. This increase in body weight with HFCS was accompanied by an increase in adipose fat, notably in the abdominal region, and elevated circulating triglyceride levels. Translated to humans, these results suggest that excessive consumption of HFCS may contribute to the incidence of obesity.

Bocarsly, Miriam E.; Powell, Elyse S.; Avena, Nicole M.; Hoebel, Bartley G.

2010-01-01

296

Pluronic L-81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein  

PubMed Central

AIM: To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed. RESULTS: Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.

Au, Wo-Shing; Lu, Li-Wei; Tam, Sidney; Ko, Otis King Hung; Chow, Billy KC; He, Ming-Liang; Ng, Samuel S; Yeung, Chung-Man; Liu, Ching-Chiu; Kung, Hsiang-Fu; Lin, Marie C

2009-01-01

297

Endogenous triglyceride-rich lipoproteins accumulate in rat plasma when competing with a chylomicron-like triglyceride emulsion for a common lipolytic pathway  

Microsoft Academic Search

The rat liver secretes very low density lipoproteins (VLDL) containing either apoB-100 or apoB-48. After oral fat intake, chylomicrons containing apoB-48 and endogenously synthesized VLDL are mixed in the blood and the triglyceride clearance from these triglyceride-rich lipoprotein species compete for the same lipolytic pathway, i.e., lipoprotein li- pase. A situation mimicking alimentary lipemia was induced by a short-term intravenous

Fredrik Karpe; Magnus Hultint

298

Interactions of triglycerides with phospholipids: Incorporation into the bilayer structure and formation of emulsions  

SciTech Connect

Interactions of carbonyl {sup 13}C-enriched triacylglycerols (TG) with phospholipid bilayers were studied by {sup 13}C NMR spectroscopy. In spectra of DPPC vesicles with TG at 40-50{degree}C, both triolein (TO) and tripalmitin (TP) had narrow carbonyl resonances, indicative of rapid motions, and chemical shifts indicative of H bonding of the TG carbonyls with solvent (H{sub 2}O) at the aqueous interfaces of the vesicle bilayer. Below the phase transition temperature of the DPPC/TG vesicles, most phospholipid peaks broadened markedly. In DPPC vesicles with TP, the TP carbonyl peaks broadened beyond detection below the transition, whereas in vesicles with TO, the TO carbonyl peaks showed little change in line width or chemical shift and no change in the integrated intensity. These properties (extent of solubility in the PC surface, conformation, solvent accessibility, and molecular mobility) may be important for enzymatic hydrolysis and protein-mediated transfer of TG. In gel-phase DPPC, the molecular mobility of the TG depends on the nature of the TG acyl chains. In the DPPC/TG mixtures studied, attempts to incorporate TG in excess of the bilayer solubility resulted in production of emulsion particles. The significance of these results for TG metabolism is discussed.

Hamilton, J.A. (Boston Univ. School of Medicine, MA (USA))

1989-03-21

299

Modeling the solid-liquid phase transition in saturated triglycerides  

NASA Astrophysics Data System (ADS)

We investigated theoretically two competing published scenarios for the melting transition of the triglyceride trilaurin (TL): those of (1) Corkery et al. [Langmuir 23, 7241 (2007)], in which the average state of each TL molecule in the liquid phase is a discotic ``Y'' conformer whose three chains are dynamically twisted, with an average angle of ~120° between them, and those of (2) Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid-state conformation of the TL molecule in the liquid phase is a nematic h*-conformer whose three chains are in a modified ``chair'' conformation. We developed two competing models for the two scenarios, in which TL molecules are in a nematic compact-chair (or ``h'') conformation, with extended, possibly all-trans, chains at low-temperatures, and in either a Y conformation or an h* conformation in the liquid state at temperatures higher than the phase-transition temperature, T*=319 K. We defined an h-Y model as a realization of the proposal of Corkery et al. [Langmuir 23, 7241 (2007)], and explored its predictions by mapping it onto an Ising model in a temperature-dependent field, performing a mean-field approximation, and calculating the transition enthalpy ?H. We found that the most plausible realization of the h-Y model, as applied to the solid-liquid phase transition in TL, and likely to all saturated triglycerides, gave a value of ?H in reasonable agreement with the experiment. We then defined an alternative h-h* model as a realization of the proposal of Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid phase exhibits an average symmetry breaking similar to an h conformation, but with twisted chains, to see whether it could describe the TL phase transition. The h-h* model gave a value of ?H that was too small by a factor of ~3-4. We also predicted the temperature dependence of the 1132 cm-1 Raman band for both models, and performed measurements of the ratios of three TL Raman bands in the temperature range of -20 °C<=T<=90 °C. The experimental results were in accord with the predictions of the h-Y model and support the proposal of Corkery et al. [Langmuir 23, 7241 (2007)] that the liquid state is made up of molecules that are each, on average, in a Y conformation. Finally, we carried out computer simulations of minimal-model TLs in the liquid phase, and concluded that although the individual TL molecules are, on average, Y conformers, long-range discotic order is unlikely to exist.

Pink, David A.; Hanna, Charles B.; Sandt, Christophe; MacDonald, Adam J.; MacEachern, Ronald; Corkery, Robert; Rousseau, Dérick

2010-02-01

300

Mechanisms of Disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease  

Microsoft Academic Search

Mean risk factor levels in various ethnic groups illustrate the potential importance of triglyceride metabolism in the risk for ischemic heart disease (IHD). Serum triglyceride concentrations are a surrogate for a range of potentially atherogenic disturbances in lipoprotein species, including increased concentrations of remnants of VLDL and chylomicron metabolism, increased small, dense LDL concentrations and reduced HDL concentrations. Differences between

Desmond G Johnston; Nishi Chaturvedi; Ian F Godsland

2007-01-01

301

Low Triglyceride, Not Low Cholesterol Concentration, Independently Predicts Poor Outcome following Acute Stroke  

Microsoft Academic Search

Background: Recent data have shown an unexpected association between poor outcome after acute stroke and lower serum cholesterol. Triglyceride concentration has been linked to coronary heart disease and stroke; however, there are currently no data on the relationship between triglyceride and stroke outcome. Such information may yield further mechanistic information on the relationship between lipids and stroke outcome. Methods: We

Christopher J. Weir; Naveed Sattar; Matthew R. Walters; Kennedy R. Lees

2003-01-01

302

Common variants associated with plasma triglycerides and risk for coronary artery disease  

PubMed Central

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10?8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayse; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tonu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkila, Kauko; Hypponen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikainen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Muller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Ines; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Doring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Goran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimaki, Terho; Lin, Shih-Yi; Lindstrom, Jaana; Loos, Ruth J.F.; Mach, Francois; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Muller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancakova, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrieres, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Jarvelin, Marjo-Riitta; Jula, Antti; Kahonen, Mika; Kaprio, Jaakko; Kesaniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; Marz, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Nj?lstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.

2013-01-01

303

Common variants associated with plasma triglycerides and risk for coronary artery disease.  

PubMed

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ay?e; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stan?áková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S

2013-11-01

304

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents  

PubMed Central

Background Although the association between the apolipoprotein A5 (APOA5) genetic variants and hypertriglyceridemia has been extensively studied, there have been few studies, particularly in children and adolescents, on the association between APOA5 genetic variants and obesity or non-high-density lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma non-HDL-C levels in Chinese child population. Methods This was a case–control study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an association study in 569 obese or overweight and 194 healthy Chinese children and adolescents. Results Genotype distributions for all polymorphisms in both cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all increased in obese or overweight patients compared to the controls. After adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence interval (CI): 1.074-2.084, P?=?0.017] higher risk for developing obesity or overweight than subjects with TT genotype, while C carriers in rs651821 had a 1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P?=?0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly different among rs662799 variants and both were higher in carriers of minor allele than in noncarriers for TG (1.64?±?0.96 vs. 1.33?±?0.67 mmol/L) (P?TG and non-high-density lipoprotein cholesterol levels for rs651821 C carriers (P?TG or non-HDL-C levels, multiple linear regression analysis was performed and the relationships were not eliminated by adjustment for age, sex and BMI. Conclusions These findings suggest the TG-raising genetic variants in the APOA5 gene may influence the susceptibility of the individual to obesity, which may also contribute to an increased risk of high non-HDL-C levels in Chinese obese children and adolescents.

2014-01-01

305

Lipid profile in women with preeclampsia: relationship between plasma triglyceride levels and severity of preeclampsia.  

PubMed

It has been hypothesized that, in preeclampsia, hypertriglyceridemia may lead to increased endothelial triglyceride accumulation that, in turn, may result in endothelial cell damage. The purpose of our study was to determine whether hypertriglyceridemia is associated with the severity of preeclampsia. We studied 29 preeclamptic patients and 46 normal pregnant women, aged 15 to 35 years, with singleton pregnancies, at 28 to 37 weeks' gestation. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured enzymatically. High-density lipoprotein cholesterol was determined using a dextran sulfate-magnesium precipitation method. Patients with mild preeclampsia had a significant increase in plasma triglyceride levels (P < .001), while patients with severe preeclampsia had triglyceride levels comparable to controls. Our findings suggest that there is no direct relationship between triglyceride levels and severity of preeclampsia. PMID:7858376

Mikhail, M S; Basu, J; Palan, P R; Furgiuele, J; Romney, S L; Anyaegbunam, A

1995-01-01

306

New chromone and triglyceride from Cucumis melo seeds.  

PubMed

Re-investigation of the MeOH extract of the seeds of Cucumis melo L. var. reticulatus (Cucurbitaceae) led to the isolation of a new chromone derivative (5,7- dihydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]chromone (5) and a triglyceride (1,3-di-(6Z,9Z)-docosa-6,9-dienoyl-2-(6Z) hexacos-6-enoylglycerol (1), together with three known compounds; alpha-spinasterol (2), stigmasta-7,22,25-trien-3-ol (3), and D:B-friedoolean-5-ene-3-beta-ol (4), are reported from this species for the first time. Their structures were determined by extensive 1D (1H, 13C, and DEPT) and 2D (1H-1H COSY, HMQC, and HMBC) NMR and mass spectral measurements. Compound 5 displayed significant cytotoxic activity against L5178Y cells, with an ED50 of 5 microM. The MeOH extract and 5 showed antioxidant activity using the DPPH assay. PMID:24689290

Ibrahim, Sabrin R M

2014-02-01

307

Modeling the liquid-solid transition in saturated triglycerides  

NASA Astrophysics Data System (ADS)

Corkery et al. have proposed that the high-temperature state of the triglyceride trilaurin (TL) is a Y-conformer, in which the three hydrocarbon chains are dynamically twisted with an average angle of ˜120 between them. Using computer simulations, we first show that the high-temperature state is indeed the Y conformation. We then develop a theory of the liquid-solid transition of this system, in which TL molecules are in a chair (h) conformation, with extended, possibly all-trans, chains at low-temperatures, and are in a Y conformation in the liquid phase at temperatures higher than the transition temperature, T* 319K. We map this ``h-Y model'' onto an Ising model in a temperature-dependent field, perform a mean-field approximation, and calculate the transition enthalpy, which is in good agreement with experiment. We also predict the temperature-dependence of the 1132 cm-1 Raman band. Our results support the proposal that the liquid state is made up of molecules in the Y conformation.

Hanna, C. B.; Pink, D. A.; MacDonald, A. J.; Thillainadarajah, K.; Corkery, R.; Rousseau, D.

2007-03-01

308

USGS Elevation Monument  

USGS Multimedia Gallery

USGS elevation monument for a level line run from Mojave, California to Keeler, California. The line ran through such places as 18-Mile Station, Dixie, Indan Wells, Little Lake, and Olancha. Elevations were based on Benecia datum....

2009-10-13

309

The Space Elevator  

NASA Astrophysics Data System (ADS)

The Space Elevator is conceived to be a carbon nanotube ribbon stretching from an Earth station in the ocean on the equator to far beyond geosynchronous altitude. This elevator co-rotates with the Earth. Climbers ascend the ribbon using power beamed from Earth to launch spacecraft in orbit or to other worlds. The requirements of the ribbon material, challenges to the building of the space elevator, deployment and the promise of the space elevator are briefly discussed in this paper.

Laubscher, Bryan E.

2005-09-01

310

Use of TG-FTIR analysis for the characterization of fuels and resources  

Microsoft Academic Search

Thermogravimetric (TG) analysis combined with Fourier Transform Infrared (FT-IR) analysis of evolved products has proven to be a powerful technique for characterization of coal, source rock, heavy hydrocarbons, biomass, waste materials, and plastics. The TG-FTIR method can be used to determine the resource potential of a material, i.e., the types of products a material is likely to produce when subjected

M. A. Serio; R. Bassilakis; P. R. Solomon

1996-01-01

311

Adjustment of Heating Rate for Maximum Resolution in TG and TMA (MaxRes)  

Microsoft Academic Search

Conventional thermogravimetric analysis (TG) uses constant heating rates to determine decomposition rates of a material and\\u000a compositional analysis. Often, the decomposition steps can not be separated clearly enough due to parallel or consecutive\\u000a reactions. If the reaction rates and the respective activation energies are enough different the TG resolution can be much\\u000a enhanced by lowering the heating rate during the

R. Riesen

1998-01-01

312

Toxoplasma gondii: bioinformatics analysis, cloning and expression of a novel protein TgIMP1.  

PubMed

Toxoplasma gondii is an obligate intracellular protozoan parasite, infecting a large variety of animals and human beings. In recent years, the study of DNA vaccine against T. gondii has made a great progress; however, few vaccines have completely controlled toxoplasmosis. Thus people started to look for more effective antigenic proteins. Here we report a novel T. gondii protein termed immune mapped protein 1 (TgIMP1). We used multiple bioinformatics approaches to predict the physical and chemical characters, signal peptide, transmembrane domain, epitope, topological structure and function of the protein, and we theoretically determined that the TgIMP1 has multiple epitopes, and with immunogenicity, suggesting that the TgIMP1 may be a vaccine candidate against toxoplasmosis. Then the gene coding TgIMP1 was obtained by PCR and connected with cloning vector. Recombinant plasmid was identified by PCR, double digestion and sequencing analysis. Then the TgIMP1 gene was directly inserted into the eukaryotic expression vector pBudCE4.1, so that the recombinant eukaryotic expression plasmid pBudCE4.1-TgIMP1 was constructed. After identification by PCR and restriction enzyme digestion, the recombinant plasmid pBudCE4.1-TgIMP1 was transfected into cells of HFF, and then identified by RT-PCR. The results showed that the eukaryotic expression plasmid pBudCE4.1-TgIMP1 was constructed and was transfected to the HFF cells successfully. PMID:23026454

Bai, Yang; He, Shenyi; Zhao, Guanghui; Chen, Lin; Shi, Na; Zhou, Huaiyu; Cong, Hua; Zhao, Qunli; Zhu, Xing-Quan

2012-12-01

313

National Elevation Dataset  

USGS Publications Warehouse

The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey (USGS). The NED is designed to provide national elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, permit edge matching, and fill sliver areas of missing data.

Geological Survey (U.S.)

1999-01-01

314

Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease  

PubMed Central

Purpose. Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1?E9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-? (A?) plaques. Results. As expected, A? plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions. Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus.

Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

2014-01-01

315

High critical temperature above T(g) may contribute to the stability of biological systems.  

PubMed Central

In this study, we characterized the molecular mobility around T(g) in sugars, poly-L-lysine and dry desiccation-tolerant biological systems, using ST-EPR, (1)H-NMR, and FTIR spectroscopy, to understand the nature and composition of biological glasses. Two distinct changes in the temperature dependence of the rotational correlation time (tau(R)) of the spin probe 3-carboxy-proxyl or the second moment (M(2)) were measured in sugars and poly-L-lysine. With heating, the first change was associated with the melting of the glassy state (T(g)). The second change (T(c)), at which tau(R) abruptly decreased over several orders of magnitude, was found to correspond with the so-called cross-over temperature, where the dynamics changed from solid-like to liquid-like. The temperature interval between T(g) and T(c) increased in the order of sucrose < trehalose < raffinose 50 degrees C, implying that the stability above T(g) improved in the same order. These differences in temperature-dependent mobilities above T(g) suggest that proteins rather than sugars play an important role in the intracellular glass formation. The exceptionally high T(c) of intracellular glasses is expected to provide excellent long-term stability to dry organisms, maintaining a slow molecular motion in the cytoplasm even at temperatures far above T(g).

Buitink, J; van den Dries, I J; Hoekstra, F A; Alberda, M; Hemminga, M A

2000-01-01

316

Rosiglitazone Reversal of Tg2576 Cognitive Deficits is Independent of Peripheral Gluco-Regulatory Status  

PubMed Central

Converging lines of evidence associate gluco-regulatory abnormalities and peroxisome-proliferator-activated receptor (PPAR) gamma function with increased risk for Alzheimer’s disease (AD). In this study, we used the Tg2576 AD mouse model to test the hypothesis that cognitive improvement following one-month of PPAR gamma agonism with rosiglitazone (RTZ) correlates with peripheral gluco-regulatory status. We assessed cognition and peripheral gluco-regulatory status of Tg2576 mice following one-month treatment with RTZ initiated prior to, coincident with, or after, the onset of peripheral gluco-regulatory abnormalities (4, 8, and 12-months of age, respectively). Whereas 5-months-old (MO) and 13 MO Tg2576 did not gain cognitive improvement after one-month treatment with RTZ, 9 MO Tg2576 mice exhibited reversal of associative learning and memory deficits. Peripheral gluco-regulatory abnormalities were improved in 9 and 13 MO Tg2576 with RTZ treatment; RTZ treatment had no effect on the normal glucose status of 5 MO Tg2576 mice. These findings suggest that RTZ-mediated cognitive improvement does not correlate with peripheral gluco-regulatory abnormalities per se, but reflects the age-dependent mechanistic differences that underlie cognitive decline in this mouse model.

Rodriguez-Rivera, Jennifer; Denner, Larry; Dineley, Kelly T.

2010-01-01

317

Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report  

SciTech Connect

Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction with specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (L{sub amb}) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/secondary displays are maximum luminance of greater than 170/100 cd/m{sup 2}, LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to ascertain the viewing cone within which contrast conformance to the GSDF is better than 30%/60% and LR is greater than 175/70 for primary/secondary displays, or alternatively, within which the on-axis contrast thresholds of the TG18-CT test pattern remain discernible. The evaluation of luminance spatial uniformity at two distinct luminance levels across the display faceplate using TG18-UNL test patterns should yield nonuniformity coefficients smaller than 30%. The resolution evaluation includes the visual scoring of the CX test target in the TG18-QC or TG18-CX test patterns, which should yield scores greater than 4/6 for primary/secondary displays. Noise evaluation includes visual evaluation of the contrast threshold in the TG18-AFC test pattern, which should yield a minimum of 3/2 targets visible for primary/secondary displays. The guidelines also include methodologies for more quantitative resolution and noise measurements based on MTF and NPS analyses. The display glare test, based on the visibility of the low-contrast targets of the TG18-GV test pattern or the measurement of the glare ratio (GR), is expected to yield scores greater than 3/1 and GRs greater than 400/150 for primary/secondary displays. Chromaticity, measured across a display faceplate or between two display devices, is expected to render a u{sup '},v{sup '} color separation of less than 0.01 for primary displays. The report offers further descriptions of prior standardization efforts, current display technologies, testing prerequisites, streamlined procedures and timelines, and TG18 test patterns.

Samei, Ehsan; Badano, Aldo; Chakraborty, Dev [Duke Advanced Imaging Laboratories, Departments of Radiology, Physics, and Biomedical Engineering, Duke University, DUMC 3302, Durham, North Carolina 27710 (United States) and FDA, CDRH (United States)] [and others

2005-04-01

318

Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet.  

PubMed

The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men (mean age, 35.7 +/- 11.4 years; body mass index, 29.0 +/- 5.1 kg/m2) were randomly assigned to either a high-CHO diet (CHO, 58%; fat, 26%; n = 23) or a high-MUFA diet (CHO, 45%; fat, 40%; MUFA, 22.5%; n = 24), which they consumed for 6 to 7 weeks. Fasting and postprandial lipemia after an oral fat load and fasting plasma apo C-III were measured at the beginning and at the end of the dietary intervention. Ad libitum consumption of the high-CHO diet induced a significant reduction in body weight (-2.6%, P < .0001), but had no impact on plasma apo C-III concentrations and on fasting and postprandial plasma TG levels. In contrast, ad libitum consumption of the high-MUFA diet also resulted in a significant reduction in body weight (-2.3%, P < .01) as well as in significant reductions in plasma apo C-III (-11%, P = .05) and fasting plasma TG (-17%, P < .01). Diet-induced variations in plasma apo C-III concentrations were correlated with changes in fasting and postprandial TG levels both in the high-CHO (r > 0.70, P < .001) and the high-MUFA groups (r > 0.42, P < .05). These results indicate that variations in plasma apo C-III levels are strong correlates of the fasting and postprandial plasma TG responses to high-MUFA and high-CHO diets. PMID:16154441

Archer, W Roodly; Desroches, Sophie; Lamarche, Benoît; Dériaz, Olivier; Landry, Nancy; Fontaine-Bisson, Bénédicte; Bergeron, Jean; Couture, Patrick; Bergeron, Nathalie

2005-10-01

319

Myocardial uptake of circulating triglycerides in nondiabetic patients with heart disease.  

PubMed

Animal studies indicate that oversupply of fatty acids derived from the action of cardiac lipoprotein lipase (LPL) on plasma lipoproteins may contribute to myocardial dysfunction. However, the contribution of circulating triglycerides to myocardial fatty acid supply in humans is not known. Six postabsorptive nondiabetic subjects who were scheduled for diagnostic coronary angiography were studied. (14)C oleate and a lipid emulsion labeled with (3)H triolein were infused to assess myocardial uptake of free fatty acids (FFAs) and triglycerides, as well as myocardial spillover of LPL-generated fatty acids. Six paired blood samples were taken from the femoral artery and the coronary sinus. Coronary sinus concentrations of unlabeled triglycerides were slightly, but not significantly, lower than arterial (P = 0.12), whereas labeled triglyceride concentrations were significantly lower in the coronary sinus than in the artery (P < 0.05; extraction fraction congruent with 11%). Triglycerides and FFAs accounted for approximately 17% and approximately 83%, respectively, of myocardial fatty acid uptake. Systemic and myocardial fractional spillover of LPL-generated fatty acids was 49.0 +/- 7% and 34.7 +/- 13%, respectively. The myocardium was a minor contributor to systemic triglyceride uptake ( approximately 3%) and a trivial contributor to systemic FFA production ( approximately 0.5%). These results indicate that circulating triglycerides may be a significant source of fatty acids for myocardial respiration. PMID:17259402

Nelson, Robert H; Prasad, Abhiram; Lerman, Amir; Miles, John M

2007-02-01

320

Tissue transglutaminase (TG-2) modified amniotic membrane: a novel scaffold for biomedical applications.  

PubMed

The amniotic membrane (AM) is considered as a natural cell culture substrate and has occasionally been exploited in regenerative medicine especially for ocular surface reconstruction and dermal wound healing applications. However, its use is limited by its relatively weak mechanical strength, difficulty during manual handling and susceptibility to proteolytic degradation in vivo. Therefore, in this study we aimed to enhance the mechanical and biological characteristics of the AM by enzymatically cross-linking it using tissue transglutaminase (TG)-a calcium-dependent enzyme capable of forming stable ?(?-glutamyl)lysine cross-linkages. Using a biological catalyst such as TG does not only prevent denaturation during sample preparation but also minimizes the potential of residual chemical cross-linking agents compared to alternative methodologies. Human AM, sourced from elective caesarean sectioning, were treated with TG, bovine serum albumin and/or a no-treatment control. Samples were then compared in terms of their physical and (scanning electron microscopy (SEM), transparency, mechanical strength, susceptibility to proteolytic degradation) biological characteristics (in vitro cell culture, activation of dendritic cells (DC)) and their in vivo biocompatibility/angiogenic capacity (chick chorioallantoic membrane assay). TG-treated AM exhibited enhanced mechanical strength and greater resistance to proteolytic/collagenase degradation compared to the control(s). SEM imaging of the TG-treated membrane summarized a significantly closer association and greater interconnectivity of individual collagen fibres yet it had no effect on the overall transparency of the AM. In vitro cell culture demonstrated no detrimental effect of TG-treatment on the AM in terms of cell attachment, spreading, proliferation and differentiation. Moreover, an 'immune response' was not elicited based on extended in vitro culture with human-monocyte-derived DC. Interestingly, the TG-treated AM still allowed angiogenesis to occur and in some instances, demonstrated an enhancement compared to the control (n = 5). We hereby demonstrate that treating the AM with the cross-linking enzyme, TG, results in a novel biomaterial with enhanced mechanical and biological characteristics. Above all, this modified membrane demonstrates greater strength, maintains in vitro cell growth, retains optical transparency and allows angiogenesis to occur without inducing an immune response. Altogether, this study demonstrates the feasibility of TG as an alternate cross-linking treatment for the production of novel biomaterials and suggests that TG-treated AM may now be more commonly exploited as a therapeutic dressing for ocular or wound applications. PMID:22652528

Chau, David Y S; Brown, Sheridan V; Mather, Melissa L; Hutter, Victoria; Tint, Naing L; Dua, Harminder S; Rose, Felicity R A J; Ghaemmaghami, Amir M

2012-08-01

321

Overexpression of Human S100B Exacerbates Cerebral Amyloidosis and Gliosis in the Tg2576 Mouse Model of Alzheimer's Disease  

PubMed Central

Alzheimer’s disease (AD) is the most common progressive dementia and is pathologically characterized by brain deposition of amyloid-? (A?) peptide as senile plaques. Inflammatory and immune response pathways are chronically activated in AD patient brains at low levels, and likely play a role in disease progression. Like microglia, activated astrocytes produce numerous acute-phase reactants and proinflammatory molecules in the AD brain. One such molecule, S100B, is highly expressed by reactive astrocytes in close vicinity of ?-amyloid deposits. We have previously shown that augmented and prolonged activation of astrocytes has a detrimental impact on neuronal survival. Furthermore, we have implicated astrocyte-derived S100B as a candidate molecule responsible for this deleterious effect. To evaluate a putative relationship between S100B and AD pathogenesis, we crossed transgenic mice overexpressing human S100B (TghuS100B mice) with the Tg2576 mouse model of AD, and examined AD-like pathology. Brain parenchymal and cerebral vascular ?-amyloid deposits and A? levels were increased in bigenic Tg2576-huS100B mice. These effects were associated with increased cleavage of the ?-C-terminal fragment of amyloid precursor protein (APP), elevation of the N-terminal APP cleavage product (soluble APP?), and activation of ?-site APP cleaving enzyme 1. In addition, double transgenic mice showed augmented reactive astrocytosis and microgliosis, high levels of S100 expression, and increased levels of proinflammatory cytokines as early as 7-9 months of age. These results provide evidence that (over)-expression of S100B acts to accelerate AD-like pathology, and suggest that inhibiting astrocytic activation by blocking S100B biosynthesis may be a promising therapeutic strategy to delay AD progression.

MORI, TAKASHI; KOYAMA, NAOKI; ARENDASH, GARY W.; HORIKOSHI-SAKURABA, YUKO; TAN, JUN; TOWN, TERRENCE

2009-01-01

322

Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations  

SciTech Connect

Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

2003-08-15

323

Liver triglyceride accumulation after chronic ethanol administration: a possible protective role of metadoxina and ubiquinone.  

PubMed

Hepatoprotective actions of metadoxina and ubiquinone have been studied in alcoholic rats by evaluating hepatic triglyceride accumulation and serum biochemical parameters of liver function. The two drug-treated groups displayed significantly lower triglyceride concentrations as compared to the ethanol-treated group. No significant differences were found among the two drug-treated and the control groups. Electron-microscopic abnormalities were found only in ethanol-treated rats. Serum biochemical parameters of liver function did not show any significant difference among all four groups. These results suggest a possible protective role of metadoxina and ubiquinone in ethanol-induced liver triglyceride accumulation. PMID:2283204

Marchi, S; Polloni, A; Costa, F; Bellini, M; Bonifazi, V; Tumino, E; Grassi, B; Romano, M R; De Bartolo, G; Bertelli, A

1990-01-01

324

Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice  

Microsoft Academic Search

Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris inTg737mutant mice.BackgroundRenal cysts and shortened cilia on renal tubular epithelia have been observed in Tg737orpk (orpk) mutant mice, suggesting a potential connection between cystogenesis and ciliogenesis. To further test this hypothesis we have characterized the progression of cystic disease and cilia expression in orpk, orpk;Tg737Rsq (orpk rescue), and Tg737?2-3?Gal;Tg737Rsq

Nicole E Brown; Noel S Murcia

2003-01-01

325

Elevated erythrocyte phosphoribosylpyrophosphate and ATP concentrations in Japanese sumo wrestlers.  

PubMed

1. Japanese sumo wrestlers have a diet rich in energy, which results in marked obesity. Their plasma urate and triglyceride levels were significantly elevated. 2. Erythrocyte phosphoribosylpyrophosphate (PRPP) and ATP concentrations in sumo wrestlers were significantly elevated when compared to the levels in control subjects. 3. There were no significant differences in erythrocyte PRPP synthetase (EC 2.7.6.1), purine nucleoside phosphorylase (EC 2.4.2.1) and hypoxanthine guanine phosphoribosyl transferase (EC 2.4.2.8) activities between sumo wrestlers and control subjects. 4. Erythrocyte adenosine kinase (EC 2.7.1.20), adenosine deaminase (EC 3.5.4.4) and adenine phosphoribosyl transferase (EC 2.4.2.7) activities in sumo wrestlers were significantly elevated. 5. It seems that sumo wrestlers have an increased turnover of adenine nucleotides which may contribute to hyperuricaemia. PMID:6185138

Nishida, Y; Akaoka, I; Hayashi, E; Miyamoto, T

1983-01-01

326

Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data  

PubMed Central

Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.

2013-01-01

327

Enhanced mineralization potential of vascular cells from SM22?-Rankl (tg) mice.  

PubMed

Vascular calcification, prevalent in diabetes and chronic kidney disease, contributes to morbidity and mortality. To investigate the effect of receptor activator of NF-kB ligand (RANKL) on vascular calcification in vivo, transgenic mice, where RANKL expression was targeted to vascular smooth muscle cells using the SM22? promoter (SM22?-Rankl ( tg )), were created. Sixteen-month-old male SM22?-Rankl ( tg ) mice had higher body weight and higher serum calcium levels but lower lumbar bone mineral density (BMD) compared with age- and gender-matched wild-type (WT) littermates. BMD of long bones, body fat (percent of weight) of the leg, and serum levels of phosphate and RANKL were not significantly different. No significant differences in these parameters were observed in female mice. Histological analysis did not reveal calcium deposits in the aortic roots of SM22?-Rankl ( tg ) mice. To analyze the osteoblastic differentiation and mineralization potentials of vascular cells, aortic smooth muscle cells (SMCs) were isolated and cultured. Results showed that SM22?-Rankl ( tg ) SMCs had higher baseline alkaline phosphatase (ALP) activity but not baseline matrix calcification. When induced by the PKA agonist forskolin, ALP activity was greater in SM22?-Rankl ( tg ) than in WT SMCs. Real-time RT-qPCR revealed higher baseline expression of ALP and ankylosis genes but lower osteoprotegerin gene in SM22?-Rankl ( tg ) SMCs. Matrix mineralization induced by inorganic phosphate or forskolin was greater in SM22?-Rankl ( tg ) than in WT SMCs. Treatment of these cells with the ALP inhibitor levamisole abolished forskolin-induced matrix mineralization but not inorganic phosphate-induced matrix mineralization. These findings suggest that RANKL overexpression in the vasculature may promote mineralization potential. PMID:23052229

Morony, S; Sage, A P; Corbin, T; Lu, J; Tintut, Y; Demer, L L

2012-12-01

328

Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.  

PubMed

Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF-?1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-?1 relative to ground controls. Total colonic TGF-?1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-?1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-?1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice. PMID:23874826

McCarville, Justin L; Clarke, Sandra T; Shastri, Padmaja; Liu, Yi; Kalmokoff, Martin; Brooks, Stephen P J; Green-Johnson, Julia M

2013-01-01

329

Spaceflight Influences both Mucosal and Peripheral Cytokine Production in PTN-Tg and Wild Type Mice  

PubMed Central

Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF-?1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-?1 relative to ground controls. Total colonic TGF-?1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-?1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-?1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

Liu, Yi; Kalmokoff, Martin; Brooks, Stephen P. J.; Green-Johnson, Julia M.

2013-01-01

330

Successful Treatment of Severe Hypertriglyceridemia with a Formula Diet Rich in Omega–3 Fatty Acids and Medium-Chain Triglycerides  

Microsoft Academic Search

Background: Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears

Annette Hauenschild; Reinhard G. Bretzel; Henning Schnell-Kretschmer; Hans-Ulrich Kloer; Philip D. Hardt; Nils Ewald

2010-01-01

331

HISTOCHEMICAL DETECTION OF TRIGLYCERIDE ESTERS WITH SPECIFIC LIPASES AND A CALCIUM-LEAD SULPHIDE TECHNIQUE1-2  

Microsoft Academic Search

A histochemical method for triglyceride esters is described that depeusds on hydrolysis of triglycerides to fatty acids by pancreatic lipase, precipitation of the released fatty acid as calcium soap and formation of lead sulphide by the conventional Gomori technique. The speci- ficity of the lipase for triglyceride was investigated by chromatography arid activatiout-inhihi- tion studies. The eutzyme preparation used hydrolyzed

C. W. M. ADAMS; Y. H. ABDULLA; B. BAYLISS

1966-01-01

332

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase.  

PubMed

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXR?), we measured LXR? expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXR? protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. PMID:24368177

Ma, Noelle; Nicholson, Catherine J; Wong, Michael; Holloway, Alison C; Hardy, Daniel B

2014-02-15

333

Cyclic nucleotides in platelets of genetically hypertriglyceridemic and hypertensive rats. Thrombin and nitric oxide responses are unrelated to plasma triglyceride levels.  

PubMed

Prague hereditary hypertriglyceridemic (HTG) rats constitute a genetic model of hypertension associated with hyperlipidemia and insulin resistance. Various cell alterations, including changes in membrane dynamics, ion transport, and decreased platelet responses to thrombin have been observed in this strain. As hypertriglyceridemia appears to be associated with reduced endothelium-dependent vasodilation and platelet aggregation, we examined whether triglycerides could modulate cell responsiveness through changes in cyclic nucleotides in platelets of HTG rats. From the age of 6 weeks, these hypertensive animals were subjected for 10 weeks to interventions that modified circulating triglycerides levels (2.17+/-0.09 mmol/l), leading to their reduction (gemfibrozil treatment, 0.87+/-0.05 mmol/l) or elevation (high fructose intake, 3.23+/-0.07 mmol/l). Basal cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents were 15% and 48% lower in isolated platelets of HTG rats than in those of Lewis controls. cAMP level was further reduced in HTG rats subjected to high fructose intake. Irrespective of their plasma triglyceride levels, the thrombin-induced increase in platelet cGMP levels present in Lewis rats was absent in platelets of HTG rats. In contrast, no strain- or treatment-related differences were observed in the magnitude or kinetics of cGMP response to exogenous nitric oxide (NO). NO-induced cGMP and cAMP changes were associated in an opposite manner with trimethylamino-diphenylhexatriene (TMA-DPH) anisotropy, a biophysical parameter that reflects the microviscosity of the outer part of the cell membrane. Our results indicate that the attenuation of platelet responsiveness to thrombin in HTG rats represents a strain difference that cannot merely be due to a difference in plasma triglyceride levels. Platelet hyporesponsiveness to agonists such as thrombin in HTG rats cannot be explained by a change in levels of inhibitory cyclic nucleotides, since they were actually found to be low and not high. PMID:11583736

Pernollet, M G; Kunes, J; Zicha, J; Devynck, M A

2001-10-01

334

Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)  

MedlinePLUS

... high triglyceride level is one part of the metabolic syndrome, a cluster of risk factors that increase the ... Familial (inherited) disorders • Type 2 diabetes or the metabolic syndrome • Pregnancy • Medications — Some “water” pills (thiazide diuretics) — Beta- ...

335

Measurement of triglycerides concentration in human serum using near-infrared transmission spectroscopy and interval PLS  

NASA Astrophysics Data System (ADS)

In order to measurement of Triglycerides in human serum with reagent-less using near-infrared (NIR) spectroscopy. Interval partial least square (iPLS) was proposed as an effective variable selection approach for multivariate calibration. For this purpose, an independent sample set was employed to evaluate the prediction ability of the resulting model. The spectrum was split into different interval. Then, the informative region of Triglycerides (1654-1746nm), in which the PLS model has a low RMSEP with 0.157mmol/L and a high R with 0.967, is selected with 18 intervals. The results show that the informative region of Triglycerides can be obtained by iPLS and applied to design the simpler reagent-less NIR instruments for inexpensive Triglycerides measurement in future.

Huang, Furong; Yu, Jianhui; Li, Shiping

2011-11-01

336

Stereospecific analysis of the major triglyceride species in the monounsaturated fraction of cocoa butter  

Microsoft Academic Search

A stereospecific analysis employing pancreatic lipase,Geotrichum candidum lipase and phospholipase A was applied to the monounsaturated triglyceride fraction of cocoa butter. Diacid triglycerides\\u000a required additional analyses involving the gas liquid chromatographic determination of the proportions of digly ceride acetates\\u000a produced by separately acetylating the ?,? and ?,?-digly cerides obtained from aG. candidum digestion mixture. Results indicated that the major triacid

J. Sampugna; R. G. Jensen

1969-01-01

337

Fatty Acid Distribution in Triglycerides of Yeasts Grown on Glucose or n-Alkanes  

Microsoft Academic Search

SUMMARY Lipid contents of yeasts grown on glucose were: Candida lipolytica, 5.4%; C. tropicalis, 9'4 %; C. utilis, 2.7 yo; Candida 107, 41 %; Hansenula anomala, 12-5 %; Rhodotorula glutinis, 2.7 % ; and R. graminis, 9-1 %. In each yeast about 80 % of the lipid consisted of triglycerides. When the triglycerides from five of the yeasts were analysed

R. F. THORPE; C. RATLEDGE

1972-01-01

338

Isoproterenol, TNF?, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes  

Microsoft Academic Search

Recently, adipose triglyceride lipase (ATGL, also called desnutrin and calcium-independent phospholipase A2 [iPLA2] ?) was isolated as a novel adipose-expressed triglyceride lipase which is downregulated in obesity and may contribute to obesity-associated metabolic disorders such as hyperlipidemia and insulin resistance. To clarify expression and regulation of this fat-derived lipase, ATGL mRNA was measured in 3T3-L1 adipocytes by quantitative real-time reverse

Susan Kralisch; Johannes Klein; Ulrike Lossner; Matthias Bluher; Ralf Paschke; Michael Stumvoll; Mathias Fasshauer

2005-01-01

339

Utilization of Triglycerides and Related Feedstocks for Production of Clean Hydrocarbon Fuels and Petrochemicals: A Review  

Microsoft Academic Search

Catalytic deoxygenation of triglycerides and related feedstocks for production of biofuels is reviewed in this paper. Green\\u000a diesel, triglyceride-based hydrocarbons in diesel boiling range, is an attractive alternative to biodiesel—a product of transesterification\\u000a of vegetable oils, particularly due to its superior fuel properties and full compatibility with current diesel fuels. Two\\u000a basic approaches to production of green diesel—(i) hydrodeoxygenation of

Iva Kubi?ková; David Kubi?ka

2010-01-01

340

Study on the flavor contribution of phospholipids and triglycerides to pork  

Microsoft Academic Search

For investigating the flavor contribution of phospholipids and triglycerides to pork, the longissimus muscle of Rongchang (RC) and PIC (bred by PIC Company of England) pig were selectively removed of intramuscular triglycerides\\u000a or total intramuscular lipids. After cooking, the flavor of different samples was compared by sensory evaluation, gas chromatographymass\\u000a spectrometry (GC-MS), and electronic nose. The results showed that removing

Ye-Chuan Huang; Hong-Jun Li; Zhi-Fei He; Ting Wang; Gang Qin

2010-01-01

341

Pioglitazone Decreases Fasting and Postprandial Endogenous Glucose Production in Proportion to Decrease in Hepatic Triglyceride Content  

PubMed Central

OBJECTIVE—Hepatic triglyceride is closely associated with hepatic insulin resistance and is known to be decreased by thiazolididinediones. We studied the effect of pioglitazone on hepatic triglyceride content and the consequent effect on postprandial endogenous glucose production (EGP) in type 2 diabetes. RESEARCH DESIGN AND METHODS—Ten subjects with type 2 diabetes on sulfonylurea therapy were treated with pioglitazone (30 mg daily) for 16 weeks. EGP was measured using a dynamic isotopic methodology after a standard liquid test meal both before and after pioglitazone treatment. Liver and muscle triglyceride levels were measured by 1H magnetic resonance spectroscopy, and intra-abdominal fat content was measured by magnetic resonance imaging. RESULTS—Pioglitazone treatment reduced mean plasma fasting glucose and mean peak postprandial glucose levels. Fasting EGP decreased after pioglitazone treatment (16.6 ± 1.0 vs. 12.2 ± 0.7 ?mol · kg?1 · min?1, P = 0.005). Between 80 and 260 min postprandially, EGP was twofold lower on pioglitazone (2.58 ± 0.25 vs. 1.26 ± 0.30 ?mol · kg?1 · min?1, P < 0.001). Hepatic triglyceride content decreased by ?50% (P = 0.03), and muscle (anterior tibialis) triglyceride content decreased by ?55% (P = 0.02). Hepatic triglyceride content was directly correlated with fasting EGP (r = 0.64, P = 0.01) and inversely correlated to percentage suppression of EGP (time 150 min, r = ?0.63, P = 0.02). Muscle triglyceride, subcutaneous fat, and visceral fat content were not related to EGP. CONCLUSIONS—Reduction in hepatic triglyceride by pioglitazone is very closely related to improvement in fasting and postprandial EGP in type 2 diabetes.

Ravikumar, Balasubramanian; Gerrard, Jean; Dalla Man, Chiara; Firbank, Michael J.; Lane, Annette; English, Philip T.; Cobelli, Claudio; Taylor, Roy

2008-01-01

342

Studies on effects of dietary fatty acids as related to their position on triglycerides  

Microsoft Academic Search

This article reviews published literature on how the stereospecific structure of dietary triglycerides may affect lipid metabolism\\u000a in humans. Animal studies have shown enhanced absorption of fatty acids in the sn-2 position of dietary triglycerides. Increasing the level of the saturated fatty acid palmitic acid in the sn-2 position (e.g., by interesterification of the fat to randomize the positions of

J. Edward Hunter

2001-01-01

343

Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels  

SciTech Connect

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

2002-09-16

344

Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia  

Microsoft Academic Search

THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospho-lipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent Mr of 88K (refs 1-3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and

Daru Sharp; Laura Blinderman; Kelly A. Combs; Bernadette Kienzle; Beverly Ricci; Karen Wager-Smith; Cleris M. Gil; Christoph W. Turck; Marie-Elizabeth Boumas; Daniel J. Rader; Lawrence P. Aggerbeck; Richard E. Gregg; David A. Gordon; John R. Wetterau

1993-01-01

345

Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats  

Microsoft Academic Search

The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause\\u000a a significant reduction in plasma lipid levels. Daily administration of a 10% (w\\/w) OFS-containing diet to normolipidemic\\u000a male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect\\u000a was observed after one week and lasted for at

Maria Fiordaliso; Nadine Kok; Jean-Pierre Desager; Fabienne Goethals; Dominique Deboyser; Marcel Roberfroid; Nathalie Delzenne

1995-01-01

346

Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels  

Microsoft Academic Search

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in â16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare

Len A. Pennacchio; Michael Olivier; Jaroslav A. Hubacek; Ronald M. Krauss; Edward M. Rubin; Jonathan C. Cohen

2002-01-01

347

Analysis of apolipoprotein A5, C3 and plasma triglyceride concentrations in genetically engineered mice  

SciTech Connect

To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either over-expressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared to over-expression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

Baroukh, Nadine; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Afzal, Veena; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

2004-03-11

348

Fatty acid chain length and degree of unsaturation are inversely associated with serum triglycerides  

Microsoft Academic Search

Little is known about the association between dietary fatty acids and serum triglyceride concentrations. Plasma fatty acids\\u000a may reflect dietary intake and can be used to study the relationship between concentrations of individual fatty acids and\\u000a serum lipids. We examined the cross-sectional relationship of plasma fatty acids with serum nonfasting triglyceride and total\\u000a cholesterol concentrations. Relative concentrations of individual plasma

Sameline Grimsgaard; Kaare H. Bønaa; Kristian S. Bjerve

2000-01-01

349

Analysis of triglycerides in food items by desorption electrospray ionization mass spectrometry.  

PubMed

The triglyceride composition and oxidation behavior of edible oil and margarine samples were analyzed by desorption electrospray ionization mass spectrometry (DESI-MS). For the characterization of the lipids, the chain length and the degree of unsaturation of the fatty acids were determined. The measurements were carried out in positive ion mode; the triglycerides were detected as alkali metal or ammonium adducts. The DESI solvent was water/methanol 1:1 (v/v); measurements were carried out both with and without the addition, as an ionizing agent, of ammonium acetate that enhances the signal intensity of the ammonium adduct ions. The spectra were interpreted for both cases and intensities were compared. Triglyceride monomers and dimers were observed in the spectra. Tandem mass spectrometric (MS/MS) measurements were carried out to determine the structure of the triglycerides. It was demonstrated that the terminal fatty acids in the sn1- or sn3-position are more likely to be cleaved than the internal fatty acid (sn2-position). Characteristic triglyceride patterns were obtained using a simple and rapid sample preparation protocol comprising the simple deposition of samples onto a glass carrier surface. The triglyceride data was analyzed by principal component analysis (PCA). The different edible oils were clearly separated and the hydrogenated derivatives were identified by their triglyceride spectra. The oxidation of the oil samples was observed and the oxidation products were detected and identified. This method provides a fast and simple technique for the detection and analysis of triglycerides in oil- or fat-containing samples ranging from food items to tissue samples. The potential application areas include nutritional studies, the food industry and cosmetics. PMID:20583323

Gerbig, Stefanie; Takáts, Zoltán

2010-08-15

350

The triglyceride lowering effect of fish oils is affected by fish consumption.  

PubMed

We investigated the efficacy of fish oils in Portuguese patients with hypertriglyceridaemia and mixed hyperlipidaemia, and the influence of fish consumption on the triglyceride lowering capacity of fish oils. Forty patients participated in this double-blind study, consisting of a 4-week dietary or wash-out baseline period after which patients were randomly assigned to receive either 12 fish oil capsules (3.6 g/day of omega 3) or similar 12 soya oil capsules per day for a period of 2 months. There were no statistically significant changes of total, HDL or LDL-cholesterol, and triglycerides. Nevertheless, triglycerides increased 19.9% with soya oil and decreased 27.8% with fish oils. Also, there was an inverse relationship (rho = -0.352) between fish consumption and fish oils effect on triglycerides, and the triglyceride lowering with fish oils increased (from 27.8% to 44.4%), reaching borderline significance, if we excluded patients consuming one or more meals with fish per day. Glucose increased 11% (P = 0.0047) with fish oils. These findings suggest that the triglyceride lowering effect of fish oils is affected by fish consumption, and confirm that fish oils increase blood glucose levels in diabetics and non-diabetics. PMID:8960947

Silva, J M; Souza, I; Silva, R; Tavares, P; Teixeira, F; Silva, P S

1996-11-15

351

A combined QXRD/TG method to quantify the phase composition of hydrated Portland cements  

SciTech Connect

A new method is reported for quantifying the mineral phases in hydrated cement pastes that is based on a combination of quantitative X-ray diffractometry (QXRD) and thermogravimetry (TG). It differs from previous methods in that it gives a precise measure of the amorphous phase content without relying on an assumed stoichiometric relationship between the principal hydration products, calcium hydroxide (CH) and calcium silicate hydrate (C–S–H). The method was successfully applied to gray and white ordinary Portland cements (GOPC and WOPC, respectively) that were cured for up to 56 days. Phase distributions determined by QXRD/TG closely matched those from gray-level analysis of backscattered scanning electron microscope (BSEM) images, whereas elemental compositions obtained for the amorphous phase by QXRD/TG agreed well with those measured by quantitative energy dispersive X-ray spectroscopy (EDS)

Soin, Alexander V.; Catalan, Lionel J.J. [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)] [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada); Kinrade, Stephen D., E-mail: stephen.kinrade@lakeheadu.ca [Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)

2013-06-15

352

Large restriction fragments containing poly-TG are highly polymorphic in a variety of vertebrates.  

PubMed Central

Southern blots of genomic DNA from a variety of species digested by restriction endonucleases having a four-bp specificity, were probed with a bovine genomic clone consisting of seven tandem poly-TG stretches separated by a 29bp linker sequence. Highly variable DNA 'fingerprint' patterns were obtained in chicken, sheep, and horse, moderately variable DNA 'fingerprints' in mouse and man, and a monomorphic pattern in Drosophila. In chicken, horse and man a (TG)10 synthetic oligonucleotide probe gave results identical to those given by the bovine probe. Furthermore, in chicken the DNA fingerprint variation showed typical Mendelian inheritance and differed from the fingerprints obtained with Jeffreys 33.6 and M13 minisatellite probes. Thus, for a variety of vertebrate species, poly-TG-containing probes can uncover useful genetic variation. Images

Kashi, Y; Tikochinsky, Y; Genislav, E; Iraqi, F; Nave, A; Beckmann, J S; Gruenbaum, Y; Soller, M

1990-01-01

353

Subpopulations of T cells (Tg and Tm) in patients with malaria.  

PubMed

In the present study we utilized rosetting techniques to enumerate the putative suppressor (Tg) and helper (Tm) T-cell subpopulations in the peripheral blood of adult Thais with malaria. A lower percentage of both Tg and Tm subpopulations and a lower number and percentage of total T cells was found in these patients during the acute period of infection than in the peripheral blood of healthy donors. However, the percentages of total T, Tg and Tm cells were higher during the convalescent period and were comparable to the values found in the peripheral blood of healthy donors. The significance of these findings are discussed. No correlations were found between the percentage of these T-cell subpopulations and the level of parasitemia or the hematocrit. PMID:6604336

Gilbreath, M J; Pavanand, K; Ussery, M A; Tulyayon, S

1983-03-01

354

Evaluation of cholesterol and triglyceride concentrations in differentiating chylous and nonchylous pleural effusions in dogs and cats.  

PubMed

Serum and pleural fluid cholesterol and triglyceride concentrations and cholesterol/triglyceride ratios were determined in 9 dogs and 9 cats with pleural effusion (8 nonchylous, 10 chylous). The pleural fluid triglyceride concentrations were significantly higher (P less than 0.05) and the pleural cholesterol/triglyceride ratios were significantly lower (P less than 0.05) in chylous effusions than in nonchylous effusions in all animals. There were no differences in serum cholesterol and triglyceride concentrations and serum cholesterol/triglyceride ratios for chylous and nonchylous effusions in either species. There also were no differences in pleural fluid cholesterol concentrations between the 2 groups in the dog or cat. It was concluded that determinations of cholesterol/triglyceride ratios may be an accurate method for helping distinguish chylous from nonchylous effusions in dogs and cats. PMID:3944008

Fossum, T W; Jacobs, R M; Birchard, S J

1986-01-01

355

The Prodomain of Toxoplasma gondii GPI-Anchored Subtilase TgSUB1 Mediates its Targeting to Micronemes  

PubMed Central

Subtilisin-like proteases have been proposed to play an important role for parasite survival in Toxoplasma gondii (Tg) and Plasmodium falciparum. The T. gondii subtilase TgSUB1 is located in the microneme, an apical secretory organelle whose contents mediate adhesion to the host during invasion. TgSUB1 is predicted to contain a glycosyl-phosphatidylinositol (GPI) anchor. This is unusual as Toxoplasma GPI-anchored proteins are targeted to the parasite's surface. In this study, we report that the subtilase TgSUB1 is indeed a GPI-anchored protein but contains dominant microneme targeting signals. Accurate targeting of TgSUB1 to the micronemes is dependent upon several factors including promoter strength and timing, accurate processing and folding. We analyzed the targeting domains of TgSUB1 using TgSUB1 deletion constructs and chimeras made between TgSUB1 and reporter proteins. The TgSUB1 prodomain is responsible for trafficking to the micronemes and is sufficient for targeting a reporter protein to the micronemes. Trafficking is dependent upon correct folding or other context-dependent conformation as the prodomain expressed alone is unable to reach the micromenes. Therefore, TgSUB1 is a novel example of a GPI-anchored protein in T. gondii that bypasses the GPI-dependent surface trafficking pathway to traffic to micronemes, specialized regulated secretory organelles.

Binder, Emily M.; Lagal, Vanessa; Kim, Kami

2009-01-01

356

Direct comparison of mechanical and electro-optic responses of a low Tg photorefractive doped polymer  

NASA Astrophysics Data System (ADS)

The temperature dependence of the electro-optic responses in a low glass transition temperature (Tg) photorefractive polymer was investigated using an ellipsometric technique. The sample was composed of a carbazole functionalized polysiloxane doped with a push-pull chalcone derivative. The results provide information on the orientational dynamics of the chromophores doping the polymer host. For this purpose, the electro-optic response is directly compared, for different temperatures above Tg, to dynamic shear compliance measurements characterizing the mechanical macroscopic behavior of the material. We demonstrate here that these orientational processes are entirely ruled by the mechanical properties of the material.

Ribierre, J.-C.; Cheval, G.; Huber, F.; Mager, L.; Fort, A.; Muller, R.; Méry, S.; Nicoud, J. F.

2002-02-01

357

Space Elevator: Stability  

Microsoft Academic Search

Many papers have been published on engineering and economic aspects of the Space Elevator. The Elevator, however, is a very special and unusual astronomical body. Its behavior in space is affected not only by the attraction of the Earth and by the “centrifugal force” but also by the attraction of the Sun and the Moon, by the detailed shape of

Lubos Perek

2008-01-01

358

[Investigating patients with differentiated thyroid carcinoma and elevated serum thyroglobulin but negative whole-body scan].  

PubMed

Findings of elevated thyroglobulin (Tg) and a negative whole-body scan (WBS) are not uncommon during the follow-up of differentiated thyroid carcinoma. In 12% of our patients submitted to thyroidectomy and radioiodine with Tg >10 ng/ml during hypothyroidism had a negative diagnostic WBS. This finding generally corresponds to a false-negative WBS. Inadequate preparation in terms of iodine exposure and insufficient elevation of TSH should be excluded. Micrometastases which do not accumulate sufficient iodine to be detected by low radioiodine activity and the loss of the capacity to express the sodium/iodine symporter explain many cases. In patients with elevated Tg, metastases can be identified after the administration of a therapeutic radioiodine dose, with this procedure being indicated in cases with Tg >10 ng/ml during hypothyroidism or >5 ng/ml after recombinant TSH, after exclusion of lung and cervical macrometastases. In the present study, 5 of 7 patients with these criteria showed ectopic uptake on post-therapy WBS. If the post-therapy scan is negative or reveals discrete uptake in the thyroid bed, other methods (e.g. FDG PET) can be performed, and the physician should not insist on radioiodine therapy. If WBS detect lymph node metastases, surgery is indicated, while in cases of diffuse lung metastases radioiodine is indicated until the occurrence of a negative WBS or normalization of stimulated Tg levels. Patients with a positive post-therapy scan may show a significant reduction in Tg, with even complete remission in some cases after radioiodine, but the impact of this treatment on mortality remains controversial. PMID:16184253

Rosário, Pedro Weslley S; Maia, Flávia Coimbra P; Barroso, Alvaro Luís; Purisch, Saulo

2005-04-01

359

Sleeve Gastrectomy in Rats Improves Post-Prandial Lipid Clearance by Reducing Intestinal Triglyceride Secretion  

PubMed Central

Background & Aims Post-prandial hyperlipidemia is a risk factor for atherosclerotic heart disease and is associated with the consumption of high-fat diets and obesity. Bariatric surgeries result in superior and more durable weight loss than dieting. These surgeries are also associated with multiple metabolic improvements, including reduced plasma lipid levels. We investigated whether the beneficial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight-independent. Methods VSG was performed on Long-Evans rats with diet-induced obesity and pair-fed and ad libitum-fed rats that received sham operations (controls). We measured fasting and post-prandial levels of plasma lipid. To determine hepatic and intestinal triglyceride secretion, we injected the lipase inhibitor poloxamer 407 alone, or before oral lipid gavage. 13C-Triolein was used to estimate post-prandial uptake of lipid in the intestine. Results Rats that received VSG and high-fat diets (HFDs) had markedly lower fasting levels of plasma triglyceride, cholesterol, and phospholipid than obese and lean (pair-fed) controls that were fed HFD. Rats that received VSG had a marked, weight-independent reduction in secretion of intestinal triglycerides. VSG did not alter total intestinal triglyceride levels or size of the cholesterol storage pool, nor did it affect the expression of genes in the intestine that control triglyceride metabolism and synthesis . VSG did not affect fasting secretion of triglyceride, liver weight, hepatic lipid storage, or transcription of genes that regulate hepatic lipid processing. Conclusions VSG reduced post-prandial levels of plasma lipid, independently of body weight. This resulted from reduced intestinal secretion of triglycerides following ingestion of a lipid meal and indicates that VSG has important effects on metabolism.

Stefater, MA; Sandoval, DA; Chambers, AP; Wilson-Perez, HE; Hofmann, SM; Jandacek, R; Tso, P; Woods, SC; Seeley, RJ

2011-01-01

360

Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant  

PubMed Central

Background Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. Methods and Findings PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n?=?3,473) and in the Go-DARTS (n?=?15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P?=?0.040) and in severely obese individuals in the Go-DARTS study (O.R. 1.37, 95% C.I. 1.13-1.66, P?=?0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction ?=?0.002). This provides evidence for the obesity interaction with I48M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study. Conclusions Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.

Pirazzi, Carlo; Burza, Maria Antonella; Adiels, Martin; Burch, Lindsay; Donnelly, Louise A.; Colhoun, Helen; Doney, Alexander S.; Dillon, John F.; Pearson, Ewan R.; McCarthy, Mark; Hattersley, Andrew T.; Frayling, Tim; Morris, Andrew D.; Peltonen, Markku; Svensson, Per-Arne; Jacobson, Peter; Boren, Jan; Sjostrom, Lars; Carlsson, Lena M. S.; Romeo, Stefano

2012-01-01

361

N-Glycoproteome of E14.Tg2a Mouse Embryonic Stem Cells  

PubMed Central

E14.Tg2a mouse embryonic stem (mES) cells are a widely used host in gene trap and gene targeting techniques. Molecular characterization of host cells will provide background information for a better understanding of functions of the knockout genes. Using a highly selective glycopeptide-capture approach but ordinary liquid chromatography coupled mass spectrometry (LC-MS), we characterized the N-glycoproteins of E14.Tg2a cells and analyzed the close relationship between the obtained N-glycoproteome and cell-surface proteomes. Our results provide a global view of cell surface protein molecular properties, in which receptors seem to be much more diverse but lower in abundance than transporters on average. In addition, our results provide a systematic view of the E14.Tg2a N-glycosylation, from which we discovered some striking patterns, including an evolutionarily preserved and maybe functionally selected complementarity between N-glycosylation and the transmembrane structure in protein sequences. We also observed an environmentally influenced N-glycosylation pattern among glycoenzymes and extracellular matrix proteins. We hope that the acquired information enhances our molecular understanding of mES E14.Tg2a as well as the biological roles played by N-glycosylation in cell biology in general.

Sun, Bingyun; Ma, Li; Yan, Xiaowei; Lee, Denis; Alexander, Vinita; Hohmann, Laura J.; Lorang, Cynthia; Chandrasena, Lalangi; Tian, Qiang; Hood, Leroy

2013-01-01

362

Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report  

Microsoft Academic Search

Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance

Ehsan Samei; Aldo Badano; Dev Chakraborty; Ken Compton; Craig Cornelius; Kevin Corrigan; Michael J. Flynn; Bradley Hemminger; Nick Hangiandreou; Jeffrey Johnson; Donna M. Moxley-Stevens; William Pavlicek; Hans Roehrig; Lois Rutz; Jeffrey Shepard; Robert A. Uzenoff; Jihong Wang; Charles E. Willis

2005-01-01

363

Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy.  

PubMed

Abnormal phosphorylation of tau protein is a common event in many neurodegenerative disorders, including Alzheimer's disease and other tauopathies. We investigated the relationship between hyperphosphorylated tau in brain extracts and mnemonic functions in rTg4510 mouse model of tauopathy. We report that rTg4510 mice showed rapid deterioration in spatial learning and memory, which paralleled a significant increase of hyperphosphorylated tau in the brain between 3 and 5.5 months of age. At 5.5 months, rTg4510 females showed significantly higher levels of hyperphosphorylated tau than males, with no evidence of differential tau transgene expression between the sexes. The increased levels of hyperphosphorylated tau in females were associated with more severe impairment in spatial learning and memory as compared to transgenic males. We also showed that within studied age range, the decrease in memory performance was accompanied by other behavioral disturbances in the water maze related to search strategy, like thigmotaxic swim and cue response. These findings suggest that the onset of abnormal tau biochemistry and coincident cognitive deficits in the rTg4510 mouse model is sex-dependent with females being affected earlier and more aggressively than males. PMID:19427061

Yue, Mei; Hanna, Amanda; Wilson, Judith; Roder, Hanno; Janus, Christopher

2011-04-01

364

NATO TG53: acoustic detection of weapon firing joint field experiment  

Microsoft Academic Search

In this paper, we discuss the NATO Task Group 53 (TG-53) acoustic detection of weapon firing field joint experiment at Yuma Proving Ground during 31 October to 4 November 2005. The participating NATO countries include France, the Netherlands, UK and US. The objectives of the joint experiments are: (i) to collect acoustic signatures of direct and indirect firings from weapons

Dale N. Robertson; Tien Pham; Michael V. Scanlon; Nassy Srour; Christian G. Reiff; Leng K. Sim; Latasha Solomon; Dorothea F. Thompson

2006-01-01

365

Advanced pulse calibration techniques for the quantitative analysis of TG–FTIR data  

Microsoft Academic Search

Two different pulse calibration techniques to estimate the total quantities of evolved gaseous substances formed in thermogravimetric (TG)–FTIR runs were compared and assessed. A gas-pulse calibration method was based on the use of a specific device able of sending a known quantity of a gaseous compound of interest to the FTIR analyzer. A second calibration method was based on the

Katia Marsanich; Federica Barontini; Valerio Cozzani; Luigi Petarca

2002-01-01

366

Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042  

PubMed Central

Background Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). Methods For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient’s objective response at the end of the study. Results Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. Conclusions These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response. Trial registration The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.

2013-01-01

367

Microsomal triglyceride transfer protein gene -493G/T polymorphism and its association with serum lipid levels in Bama Zhuang long-living families in China  

PubMed Central

Background The -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China. Methods The MTP -493G/T was genotyped by PCR-restriction fragment length polymorphism in 391 Bama Zhuang long-lived families (BLF, n?=?1467, age 56.60?±?29.43 years) and four control groups recruited from Bama and out-of-Bama area with or without a familial history of exceptional longevity: Bama non-long-lived families (BNLF, n?=?586, age 44.81?±?26.83 years), Bama non-Zhuang long-lived families (BNZLF, n?=?444, age 52.09?±?31.91 years), Pingguo long-lived families (PLF, n?=?658, age 50.83?±?30.30 years), and Pingguo non-long-lived families (PNLF, n?=?539, age 38.74?±?24.69 years). Correlation analyses between genotypes and serum lipid levels and longevity were then performed. Results No particularly favorable lipoprotein and clinical phenotypes were seen in BLF as compared to general families in the same area. Instead, the levels of total cholesterol (TC), TG, LDL-C, and the prevalence of dyslipidemia were significantly higher in the three Bama families as compared to the two non-Bama families (P??0.05 for all), but the TT genotype tended to enrich in the three long-lived cohorts from both areas. In addition, the individuals harboring TT genotype exhibited lower LDL-C and TC levels in the overall populations and Bama populations with a region- and sex-specific pattern. Multiple linear regression analyses unraveled that LDL-C levels were correlated with genotypes in Bama combined population, BNLF, and the total population (P?

2012-01-01

368

Local confidence limits for IMRT and VMAT techniques: a study based on TG119 test suite.  

PubMed

The aim of this study was to generate a local confidence limit (CL) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used at Waikato Regional Cancer Centre. This work was carried out based on the American Association of Physicists in Medicine (AAPM) Task Group (TG) 119 report. The AAPM TG 119 report recommends CLs as a bench mark for IMRT commissioning and delivery based on its multiple institutions planning and dosimetry comparisons. In this study the locally obtained CLs were compared to TG119 benchmarks. Furthermore, the same bench mark was used to test the capabilities and quality of the VMAT technique in our clinic. The TG 119 test suite consists of two primary and four clinical tests for evaluating the accuracy of IMRT planning and dose delivery systems. Pre defined structure sets contoured on computed tomography images were downloaded from AAPM website and were transferred to a locally designed phantom. For each test case two plans were generated using IMRT and VMAT optimisation. Dose prescriptions and planning objectives recommended by TG119 report were followed to generate the test plans in Eclipse Treatment Planning System. For each plan the point dose measurements were done using an ion chamber at high dose and low dose regions. The planar dose distribution was analysed for percentage of points passing the gamma criteria of 3%/3 mm, for both the composite plan and individual fields of each plan. The CLs were generated based on the results from the gamma analysis and point dose measurements. For IMRT plans, the CLs obtained were (1) from point dose measurements: 2.49% at high dose region and 2.95% for the low dose region (2) from gamma analysis: 2.12% for individual fields and 5.9% for the composite plan. For VMAT plans, the CLs obtained were (1) from point dose measurements: 2.56% at high dose region and 2.6% for the low dose region (2) from gamma analysis: 1.46% for individual fields and 0.8% for the composite plan. All these CLs were well within the TG119 recommended bench marks. Based on these analysis which were performed in line with the TG119 recommendations, it is evident that the local clinic has commissioned IMRT and VMAT techniques with adequate accuracy. These results compliment our clinical confidence of using IMRT and VMAT routinely and expanding to different clinical sites. PMID:24414337

Thomas, M; Chandroth, M

2014-03-01

369

The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26  

Microsoft Academic Search

The multifunctional enzyme tissue transglutaminase (TG2) is reported to both mediate and inhibit tumour progression. To elucidate\\u000a these different roles of TG2, we established a series of stable-transfected mouse colon carcinoma CT26 cells expressing a\\u000a catalytically active (wild type) and a transamidating-inactive TG2 (Cys277Ser) mutant. Comparison of the TG2-transfected cells\\u000a with the empty vector control indicated no differences in cell

Panayiotis Kotsakis; Zhuo Wang; Russell John Collighan; Martin Griffin

370

TG2-mediated activation of ?-catenin signaling has a critical role in warfarin-induced vascular calcification  

PubMed Central

Objective Accumulating experimental evidence implicates ?-catenin signaling and enzyme transglutaminase 2 (TG2) in the progression of vascular calcification, and our previous studies have shown that TG2 can activate ?-catenin signaling in vascular smooth muscle cells (VSMCs). Here we investigated the role of the TG2/?-catenin signaling axis in vascular calcification induced by warfarin. Methods and Results Warfarin-induced calcification in rat A10 VSMCs is associated with the activation of ?-catenin signaling and is independent from oxidative stress. The canonical ?-catenin inhibitor Dkk1, but not the Wnt antagonist Wif-1,prevents warfarin-induced activation of ?-catenin, calcification, and osteogenic trans-differentiation in VSMCs. TG2 expression and activity are increased in warfarin-treated cells, in contrast to canonical Wnt ligands. Vascular cells with genetically or pharmacologically reduced TG2 activity fail to activate ?-catenin in response to warfarin. Moreover, warfarin-induced calcification is significantly reduced on the background of attenuated TG2 both in vitro and in vivo. Conclusions TG2 is a critical mediator of warfarin-induced vascular calcification that acts through the activation of ?-catenin signaling in VSMCs. Inhibition of canonical ?-catenin pathway or TG2 activity prevents warfarin-regulated calcification, identifying the TG2/?-catenin axis as a novel therapeutic target in vascular calcification.

Beazley, Kelly E.; Deasey, Stephanie; Lima, Florence; Nurminskaya, Maria V.

2011-01-01

371

Synaptic alterations in the rTg4510 mouse model of tauopathy  

PubMed Central

Synapse loss, rather than the hallmark amyloid-? (A?) plaques or tau filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer disease (AD) brain. The role of A? in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau over-expression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multi-photon in-vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons suggesting these cells may be particularly vulnerable to tau-induced degeneration. Post-mortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together these data show morphological and biochemical synaptic consequences in response to tau over-expression in the rTg4510 mouse model.

Kopeikina, Katherine J; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Carlson, George A; Pitstick, Rose; Hyman, Bradley T; Spires-Jones, Tara L

2013-01-01

372

TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells  

PubMed Central

The phylum Apicomplexa comprises a group of obligate intracellular parasites of broad medical and agricultural significance, including Toxoplasma gondii and the malaria-causing Plasmodium spp. Key to their parasitic lifestyle is the need to egress from an infected cell, actively move through tissue, and reinvade another cell, thus perpetuating infection. Ca2+-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme organelles and activation of the force-generating actomyosin-based motor. Here we show that a plant-like Calcium-Dependent Protein Kinase (CDPK) in T. gondii, TgCDPK3, which localizes to the inner side of the plasma membrane, is not essential to the parasite but is required for optimal in vitro growth. We demonstrate that TgCDPK3, the orthologue of Plasmodium PfCDPK1, regulates Ca2+ ionophore- and DTT-induced host cell egress, but not motility or invasion. Furthermore, we show that targeting to the inner side of the plasma membrane by dual acylation is required for its activity. Interestingly, TgCDPK3 regulates microneme secretion when parasites are intracellular but not extracellular. Indeed, the requirement for TgCDPK3 is most likely determined by the high K+ concentration of the host cell. Our results therefore suggest that TgCDPK3's role differs from that previously hypothesized, and rather support a model where this kinase plays a role in rapidly responding to Ca2+ signaling in specific ionic environments to upregulate multiple processes required for gliding motility.

McCoy, James M.; Whitehead, Lachlan; van Dooren, Giel G.; Tonkin, Christopher J.

2012-01-01

373

A Nanotube Space Elevator  

NSDL National Science Digital Library

In this video adapted from NOVA scienceNOW, find out about the discovery of a new building material, the carbon nanotube, whose physical properties could theoretically enable the creation of a 22,000-mile elevator to space.

Foundation, Wgbh E.

2008-09-08

374

Elevated Temperature Biaxial Fatigue.  

National Technical Information Service (NTIS)

A three year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed towar...

E. H. Jordan

1984-01-01

375

The A>T polymorphism of the tribbles homolog 1 gene is associated with serum triglyceride concentrations in Japanese community-dwelling women.  

PubMed

Recent genome-wide association studies have identified Tribbles homolog 1 (TRIB1) as one of the candidate genes associated with lipid profiles. TRIB1 is known to interact with MAP kinases, thereby regulating their activities. The single nucleotide polymorphism rs2954029 of TRIB1 is located within an intron and is associated with lipid profiles. The aim of the present study is to investigate the TRIB1 rs2954029 (A>T polymorphism) with conventional predictors of coronary artery diseases such as carotid intima-media thickness (CIMT) and cardio-ankle vascular index (CAVI), and with lipid profiles in general population. This study enrolled 2,581 Japanese adults, 942 men and 1,639 women with a median age of 68 years (range 29 to 94 years), who participated in a screening program for the general population living in Goto City, Nagasaki Prefecture, Japan from 2008 to 2010. For the determination of TRIB1 rs2954029 genotypes, the polymerase chain reaction method was used. The differences in each parameter among the TRIB1 rs2954029 genotypes were evaluated using analysis of covariance. Genotype frequencies of TRIB1 rs2954029 in all participants were 25.5% for AA, 50.4% for AT, and 24.0% for TT. In women, the AA genotype showed significantly higher log triglyceride (TG) concentrations than the AT genotype (P = 0.004) and the AT + TT genotypes (P = 0.004). On the other hand, there were no associations with CIMT and CAVI among the TRIB1 rs2954029 genotypes. In conclusion, the TRIB1 rs2954029 is associated with serum TG concentrations in Japanese community-dwelling women. PMID:24910200

Ikeoka, Toshiyuki; Hayashida, Naomi; Nakazato, Mio; Sekita, Takaharu; Murata-Mori, Fumi; Ando, Takao; Abiru, Norio; Yamasaki, Hironori; Kudo, Takashi; Maeda, Takahiro; Kawakami, Atsushi; Takamura, Noboru

2014-01-01

376

Biopolymer from microbial assisted in situ hydrolysis of triglycerides and dimerization of fatty acids.  

PubMed

The present study demonstrates biopolymer production by in situ bio-based dimerization of fatty acids by microorganism isolated from marine sediments. Microbial isolate grown in Zobell medium in the presence of triglycerides for the period of 24-240 h at 37 degrees C, hydrolyze the applied triglycerides and sequentially dimerized the hydrolyzed products and subsequently polymerized and transformed to a biopolymer having appreciable adhesive properties. Physical (nature, odour, stickyness and tensile strength), chemical (instrumentation) and biochemical (cell free broth) methods of analyses carried out provided the hypotheses involved in the formation of the product as well as the nature of the product formed. Results revealed, lipolytic enzymes released during initial period of growth and the biosurfactant production during later period, respectively, hydrolyze the applied triglycerides and initiate the dimerization and further accelerated when the incubation period extended. The existence and the non-existence of in situ hydrolysis of various triglycerides followed by dimerization and polymerization and the mechanism of transformation of triglycerides to biopolymer are discussed in detail. PMID:19720526

Kavitha, V; Radhakrishnan, N; Madhavacharyulu, E; Sailakshmi, G; Sekaran, G; Reddy, B S R; Rajkumar, G Suseela; Gnanamani, Arumugam

2010-01-01

377

Genomic interval engineering of mice identified a novel modulator of triglyceride production  

SciTech Connect

To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.

1999-10-01

378

Mechanical behavior of a Zr-based metallic glass at elevated temperature under high strain rate  

NASA Astrophysics Data System (ADS)

In current work, the mechanical behavior of a Zr-based bulk metallic glass at elevated temperatures (from 423 to 683 K) under high strain rate (from 5000 to 104 s-1) is investigated by an improved split Hopkinson pressure bar apparatus. Experimental results reveal that the failure stress goes down along with elevated temperature, while the strain rate dependency is relatively small. Furthermore, three different fracture modes are observed along with elevated temperature by scanning electron microscope (SEM). SEM observation results also indicate that the fractured specimen has been crystallized at temperature near Tg and the embrittlement caused by crystallization is attributed to the fracture mode changing.

Liu, W. D.; Liu, K. X.

2010-08-01

379

Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.  

PubMed

Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNF? production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages. PMID:24129399

Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

2013-12-01