Science.gov

Sample records for high-fat meal impairs

  1. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

    PubMed Central

    Harvey, Jennifer C.; Roseguini, Bruno T.; Goerger, Benjamin M.; Fallon, Elizabeth A.

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT. PMID:27595112

  2. The effect of acute exercise on endothelial function following a high-fat meal.

    PubMed

    Padilla, Jaume; Harris, Ryan A; Fly, Alyce D; Rink, Lawrence D; Wallace, Janet P

    2006-10-01

    The transient impairment of endothelial function following a high-fat meal is well established. Brachial artery flow-mediated dilation (FMD) decreases between 2 and 6 h post ingestion. Whether this impairment can be reduced with acute aerobic exercise has not been investigated. The purpose of this study was to investigate if a single sustained aerobic exercise session can counteract the postprandial attenuation in brachial artery FMD associated with the ingestion of a high-fat meal. Eight apparently healthy adults (five men, three women), age 25.5 +/- 0.8 years, performed three treatment conditions in a counter-balanced design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one session of aerobic exercise presented 2 h after ingesting a high-fat meal (HFM-EX). The examination of brachial artery FMD was performed at baseline and 4 h following the ingestion of the meal for each treatment condition. A 3 x 2 (treatment x time) repeated measures ANOVA exhibited a significant interaction (P = 0.019). Preprandial FMDs were similar (P = 0.863) among all three treatment conditions. The FMDs following the LFM (7.18 +/- 1.31%) and HFM-EX (8.72 +/- 0.94%) were significantly higher (P = 0.001) than the FMD following the HFM (4.29 +/- 1.64%). FMD was significantly elevated above preprandial values following the HFM-EX (5.61 +/- 1.54 to 8.72 +/- 0.94%, P = 0.005) but was unchanged following the LFM (6.17 +/- 0.94 to 7.18 +/- 1.31%, P = 0.317) and the HFM (5.73 +/- 1.23 to 4.29 +/- 1.64%, P = 0.160). These findings suggest that a single aerobic exercise session cannot only counteract the postprandial endothelial dysfunction induced by the ingestion of a high-fat meal, but also increase brachial artery FMD in apparently healthy adults.

  3. Effects of prior acute exercise on circulating cytokine concentration responses to a high-fat meal.

    PubMed

    Brandauer, Josef; Landers-Ramos, Rian Q; Jenkins, Nathan T; Spangenburg, Espen E; Hagberg, James M; Prior, Steven J

    2013-08-01

    High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before and 4 h after ingestion of a high-fat meal either with or without ∼50 min of endurance exercise at 70% of VO2 max on the preceding day. In response to the high-fat meal, lower leptin and higher VEGF, bFGF, IL-6, and IL-8 concentrations were evident (P < 0.05 for all). There was no effect of the high-fat meal on PlGF, TNF-α, or RBP4 concentrations. We found lower leptin concentrations with prior exercise (P < 0.05) and interactive effects of prior exercise and the high-fat meal on sFlt-1 (P < 0.05). The high-fat meal increased IL-6 by 59% without prior exercise and 218% with prior exercise (P < 0.05). In conclusion, a prior bout of endurance exercise does not affect all high-fat meal-induced changes in circulating cytokines, but does affect fasting or postprandial concentrations of IL-6, leptin, and sFlt-1. These data may reflect a salutary effect of prior exercise on metabolic responses to a high-fat meal.

  4. Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals.

    PubMed

    Parry, Siôn A; Smith, Jennifer R; Corbett, Talitha R B; Woods, Rachel M; Hulston, Carl J

    2017-01-01

    Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.

  5. Inflammatory and metabolic responses to high-fat meals with and without dairy products in men.

    PubMed

    Schmid, Alexandra; Petry, Nicolai; Walther, Barbara; Bütikofer, Ueli; Luginbühl, Werner; Gille, Doreen; Chollet, Magali; McTernan, Philip G; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François P; Laederach, Kurt; Vergères, Guy

    2015-06-28

    Postprandial inflammation is an important factor for human health since chronic low-grade inflammation is associated with chronic diseases. Dairy products have a weak but significant anti-inflammatory effect on postprandial inflammation. The objective of the present study was to compare the effect of a high-fat dairy meal (HFD meal), a high-fat non-dairy meal supplemented with milk (HFM meal) and a high-fat non-dairy control meal (HFC meal) on postprandial inflammatory and metabolic responses in healthy men. A cross-over study was conducted in nineteen male subjects. Blood samples were collected before and 1, 2, 4 and 6 h after consumption of the test meals. Plasma concentrations of insulin, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and C-reactive protein (CRP) were measured at each time point. IL-6, TNF-α and endotoxin concentrations were assessed at baseline and endpoint (6 h). Time-dependent curves of these metabolic parameters were plotted, and the net incremental AUC were found to be significantly higher for TAG and lower for CRP after consumption of the HFM meal compared with the HFD meal; however, the HFM and HFD meals were not different from the HFC meal. Alterations in IL-6, TNF-α and endotoxin concentrations were not significantly different between the test meals. The results suggest that full-fat milk and dairy products (cheese and butter) have no significant impact on the inflammatory response to a high-fat meal.

  6. Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects

    PubMed Central

    Deplanque, Xavier; Muscente-Paque, Delphine; Chappuis, Eric

    2016-01-01

    Background Low-density lipoprotein (LDL) oxidation is a risk factor for atherosclerosis. Lycopene and tomato-based products have been described as potent inhibitors of LDL oxidation. Objectives To evaluate the effect of a 2-week supplementation with a carotenoid-rich tomato extract (CRTE) standardized for a 1:1 ratio of lycopene and phytosterols, on post-prandial LDL oxidation after a high-fat meal. Design In a randomized, double-blind, parallel-groups, placebo-controlled study, 146 healthy normal weight individuals were randomly assigned to a daily dose of CRTE standardized for tomato phytonutrients or placebo during 2 weeks. Oxidized LDL (OxLDL), glucose, insulin, and triglyceride (TG) responses were measured for 8 h after ingestion of a high-fat meal before and at the end of intervention. Results Plasma lycopene, phytofluene, and phytoene were increased throughout the study period in the CRTE group compared to placebo. CRTE ingestion significantly improved changes in OxLDL response to high-fat meal compared to placebo after 2 weeks (p<0.0001). Changes observed in glucose, insulin, and TG responses were not statistically significant after 2 weeks of supplementation, although together they may suggest a trend of favorable effect on metabolic outcomes after a high-fat meal. Conclusions Two-week supplementation with CRTE increased carotenoids levels in plasma and improved oxidized LDL response to a high-fat meal in healthy normal weight individuals. PMID:27707453

  7. Effects of a high-fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteers.

    PubMed

    Schinkovitz, A; Dittrich, P; Wascher, T C

    2001-07-01

    High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous-occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1.05 +/- 0.61 mmol l(-1) in the fasting state to peak postprandial values of 1.94 +/- 0.41 mmol l(-1) (P < 0.001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19.6 +/- 2.4 ml min(-1) (100 ml)(-1). Two hours after ingestion of the test meal peak RH was transiently reduced to 16.8 +/- 2.2 ml min(-1) (100 ml)(-1) (P < 0.05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 +/- 26 micromol l(-1) at baseline) or on plasma peroxides measured as H2O2 equivalents (469 +/- 117 micromol l(-1)). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress.

  8. CCK(1) receptor is essential for normal meal patterning in mice fed high fat diet.

    PubMed

    Donovan, Michael J; Paulino, Gabriel; Raybould, Helen E

    2007-12-05

    Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK(1)Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK(1)R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK(1)R gene is deleted. CCK(1)R(-/-) and CCK(1)R(+/+) mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 h each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK(1)R(-/-) compared to CCK(1)R(+/+) mice. However, meal size was larger in the CCK(1)R(-/-) mice compared to CCK(1)R(+/+) mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK(1)R(-/-) mice fed a HF diet had a 75% decrease in the time to 1st meal compared to CCK(1)R(+/+) mice following a 6 h fast. These data suggest that lack of the CCK(1)R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK(1)R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.

  9. Effects of training status on the metabolic responses to high carbohydrate and high fat meals.

    PubMed

    Bowden, V L; McMurray, R G

    2000-03-01

    The purpose of this study was to determine if there is a difference between the way in which aerobically trained and untrained women metabolize fats and carbohydrates at rest in response to either a high-fat or high-carbohydrate meal. Subjects, 6 per group, were fed a high CHO meal (2068 kJ, 76% CHO, 23% fat, 5% protein) and a high fat meal (2093 kJ, 21% CHO, 72% fat, 8% protein) in counterbalanced order. Resting metabolic rate (RMR) was measured every half-hour for 5 hours. RMR was similar between groups. However, after ingesting a high CHO meal, trained subjects had a peak in metabolism at minute 60, not evident in the untrained subjects. In addition, postprandial RER from minutes 120-300 were lower and fat use was greater after the high CHO meal for the trained subjects. These results suggest that aerobically trained women have an accelerated CHO uptake and overall lower CHO oxidation following the ingestion of a high CHO meal.

  10. High-fat meals reduce 24-h circulating leptin concentrations in women.

    PubMed

    Havel, P J; Townsend, R; Chaump, L; Teff, K

    1999-02-01

    Leptin induces weight loss in rodents via its effects on food intake and energy expenditure. High-fat diets induce weight gain, but the mechanism is not well understood. Previous studies have not found an effect of dietary fat content on fasting leptin. There is a nocturnal increase of leptin, however, which is related to insulin responses to meals. We have reported that adipocyte glucose utilization is involved in insulin-induced leptin secretion in vitro. Accordingly, high-fat, low-carbohydrate (HF/LC) meals, which induce smaller insulin and glucose responses, would produce lower leptin concentrations than low-fat, high-carbohydrate (LF/HC) meals. Blood samples were collected every 30-60 min for 24 h from 19 normal-weight (BMI, 24.2 +/- 0.7 kg/m2; percent body fat = 31 +/- 1%) women on 2 days (10 days apart) during which the subjects were randomized to consume three isocaloric 730-kcal meals containing either 60/20 or 20/60% of energy as fat/carbohydrate. Overall insulin and glycemic responses (24-h area under the curve [AUC]) were reduced by 55 and 61%, respectively, on the HF/LC day (P < 0.0001). During LF/HC feeding, there were larger increases of leptin 4-6 h after breakfast (38 +/- 7%, P < 0.001) and lunch (78 +/- 14%, P < 0.001) than after HF/LC meals (both P < 0.02). During LF/HC feeding, leptin increased from a morning baseline of 10.7 +/- 1.6 ng/ml to a nocturnal peak of 21.3 +/- 1.3 ng/ml (change, 10.6 +/- 1.3 ng/ml; percent change, 123 +/- 16%; P < 0.0001). The amplitudes of the nocturnal rise of leptin and the 24-h leptin AUC were 21 +/- 8% (P < 0.005) and 38 +/- 12% (P < 0.0025) larger, respectively, on the LF/HC day. In summary, consumption of HF/LC meals results in lowered 24-h circulating leptin concentrations. This result may be a consequence of decreased adipocyte glucose metabolism. Decreases of 24-h circulating leptin could contribute to the weight gain during consumption of high-fat diets.

  11. Rats acquire stronger preference for flavors consumed towards the end of a high-fat meal.

    PubMed

    Myers, Kevin P

    2013-02-17

    Rats learn to prefer flavors associated with postingestive effects of nutrients. The physiological signals underlying this postingestive reward are unknown. We have previously shown that rats readily learn to prefer a flavor that was consumed early in a multi-flavored meal when glucose is infused intragastrically (IG), suggesting rapid postingestive reward onset. The present experiments investigate the timing of postingestive fat reward, by providing distinctive flavors in the first and second halves of meals accompanied by IG fat infusion. Learning stronger preference for the earlier or later flavor would indicate when the rewarding postingestive effects are sensed. Rats consumed sweetened, calorically-dilute flavored solutions accompanied by IG high-fat infusion (+ sessions) or water (- sessions). Each session included an "Early" flavor for 8min followed by a "Late" flavor for 8min. Learned preferences were then assessed in two-bottle tests (no IG infusion) between Early(+) vs. Early(-), Late(+) vs. Late(-), Early(+) vs. Late(+), and Early(-) vs. Late(-). Rats only preferred Late(+), not Early(+), relative to their respective (-) flavors. In a second experiment rats trained with a higher fat concentration learned to prefer Early(+) but more strongly preferred Late(+). Learned preferences were evident when rats were tested deprived or recently satiated. Unlike with glucose, ingested fat appears to produce a slower-onset rewarding signal, detected later in a meal or after its termination, becoming more strongly associated with flavors towards the end of the meal. This potentially contributes to enhanced liking for dessert foods, which persists even when satiated.

  12. Cognitive Impairment Following High Fat Diet Consumption is Associated with Brain Inflammation

    PubMed Central

    Pistell, Paul J.; Morrison, Christopher D.; Gupta, Sunita; Knight, Alecia G.; Keller, Jeffrey N.; Ingram, Donald K.; Bruce-Keller, Annadora J.

    2009-01-01

    C57Bl/6 mice were administered a high fat, Western diet (WD, 41% fat) or a very high fat lard diet (HFL, 60% fat), and evaluated for cognitive ability using the Stone T-maze and for biochemical markers of brain inflammation. WD consumption resulted in significantly increased body weight and astrocyte reactivity, but not impaired cognition, microglial reactivity, or heightened cytokine levels. HFL increased body weight, and impaired cognition, increased brain inflammation, and decreased BDNF. Collectively, these data suggest that while different diet formulations can increase body weight, the ability of high fat diets to disrupt cognition is linked to brain inflammation. PMID:20004026

  13. Changes in Expression of Genes Regulating Airway Inflammation Following a High-Fat Mixed Meal in Asthmatics

    PubMed Central

    Li, Qian; Baines, Katherine J.; Gibson, Peter G.; Wood, Lisa G.

    2016-01-01

    Consumption of a high fat meal can increase neutrophilic airway inflammation in asthma subjects. This study investigates the molecular mechanisms driving airway neutrophilia following a high fat meal in asthmatics. Subjects with asthma (n = 11) and healthy controls (n = 8) consumed a high-fat/energy meal, containing total energy (TE) of 3846 kJ and 48 g of total fat (20.5 g saturated). Sputum was induced at 0 and 4 h, and gene expression was examined by microarray and quantitative real-time PCR (qPCR). Following the high fat dietary challenge, 168 entities were significantly differentially expressed greater than >1.5 fold in subjects with asthma, whereas, in healthy controls, only 14 entities were differentially expressed. Of the 168 genes that were changed in asthma, several biological processes were overrepresented, with 25 genes involved in “immune system processes”. qPCR confirmed that S100P, S100A16, MAL and MUC1 were significantly increased in the asthma group post-meal. We also observed a strong correlation and a moderate correlation between the change in NLRP12 and S100A16 gene expression at 4 h compared to baseline, and the change in total and saturated non-esterified plasma fatty acid levels at 2 h compared to baseline. In summary, our data identifies differences in inflammatory gene expression that may contribute to increased airway neutrophilia following a high fat meal in subjects with asthma and may provide useful therapeutic targets for immunomodulation. This may be particularly relevant to obese asthmatics, who are habitually consuming diets with a high fat content. PMID:26751474

  14. Effect of a high-fat meal on the pharmacokinetics of 300-milligram posaconazole in a solid oral tablet formulation.

    PubMed

    Kersemaekers, Wendy M; Dogterom, Peter; Xu, Jialin; Marcantonio, Eugene E; de Greef, Rik; Waskin, Hetty; van Iersel, Marlou L P S

    2015-01-01

    Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release tablet formulation of posaconazole at the proposed clinical dose of 300 mg once daily in a randomized, open-label, single-dose, two-period crossover study with 18 healthy volunteers. When a single 300-mg dose of posaconazole in tablet form (3 tablets × 100 mg) was administered with a high-fat meal, the posaconazole area under the concentration-time curve from 0 to 72 h (AUC0-72) and maximum concentration in plasma (Cmax) increased 51% and 16%, respectively, compared to those after administration in the fasted state. The median time to Cmax (Tmax) shifted from 5 h in the fasted state to 6 h under fed conditions. No serious adverse events were reported, and no subject discontinued the study due to an adverse event. Six of the 18 subjects reported at least one clinical adverse event; all of these events were mild and short lasting. The results of this study demonstrate that a high-fat meal only modestly increases the mean posaconazole exposure (AUC), ∼1.5-fold, after administration of posaconazole tablets, in contrast to the 4-fold increase in AUC observed previously for a posaconazole oral suspension given with a high-fat meal.

  15. Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding.

    PubMed

    Gotthardt, Juliet D; Bello, Nicholas T

    2017-03-03

    Alternate day, intermittent fasting (IMF) can be an effective weight loss strategy. However, the effects of IMF on eating behaviors are not well characterized. We investigated the acute and residual effects of IMF for weight loss on meal patterns in adult obese male C57BL/6 mice. After 8weeks of ad libitum high-fat diet to induce diet-induced obesity (DIO), mice were either continued on ad libitum high-fat diet (HFD) or placed on one of 5 diet strategies for weight loss: IMF of high-fat diet (IMF-HFD), pair-fed to IMF-HFD group (PF-HFD), ad libitum low-fat diet (LFD), IMF of low-fat diet (IMF-LFD), or pair-fed to IMF-LFD group (PF-LFD). After the 4-week diet period, all groups were refed the high-fat diet for 6weeks. By the end of the diet period, all 5 groups had lost weight compared with HFD group, but after 6weeks of HFD re-feeding all groups had similar body weights. On (Day 2) of the diet period, IMF-HFD had greater first meal size and faster eating rate compared with HFD. Also, first meal duration was greater in LFD and IMF-LFD compared with HFD. At the end of the diet period (Day 28), the intermittent fasting groups (IMF-HFD and IMF-LFD) had greater first meal sizes and faster first meal eating rate compared with their respective ad libitum fed groups on similar diets (HFD and LFD). Also, average meal duration was longer on Day 28 in the low-fat diet groups (LFD and IMF-LFD) compared with high-fat diet groups (HFD and IMF-HFD). After 6weeks of HFD re-feeding (Day 70), there were no differences in meal patterns in groups that had previously experienced intermittent fasting compared with ad libitum fed groups. These findings suggest that meal patterns are only transiently altered during alternate day intermittent fasting for weight loss in obese male mice.

  16. Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome

    PubMed Central

    Katcher, Heather I.; Kunselman, Allen R.; Dmitrovic, Romana; Demers, Laurence M.; Gnatuk, Carol L.; Kris-Etherton, Penny M.; Legro, Richard S.

    2009-01-01

    Objective To determine the effect of meal composition on postprandial testosterone levels in women with polycystic ovary syndrome (PCOS). Design Randomized, crossover design. Setting Academic research center. Patients Fifteen women with PCOS. Intervention We evaluated changes in testosterone, sex hormone binding globulin (SHBG), DHEA-S, cortisol, glucose, and insulin for six hours after a high-fat, Western meal (HIFAT) (62% fat, 24% carbohydrate, 1g fiber) and an isocaloric low-fat, high-fiber meal (HIFIB) (6% fat, 81% carbohydrate, 27g fiber). Main outcome measure Change in testosterone. Results Testosterone decreased 27% within two hours after both meals (P<0.001). However, testosterone remained below premeal values for four hours after the HIFIB meal (P<0.004) and six hours after the HIFAT meal (P<0.004). Insulin was two fold higher for two hours after the HIFIB meal compared with the HIFAT meal (P<0.03). Glucose was higher for one hour after the HIFIB meal compared with the HIFAT meal (P<0.003). DHEA-S decreased 8−10% within 2−3 hours after both meals, then increased over the remainder of the study period (P<0.001). Cortisol decreased over the 6-hour period after both meals (P<0.001). Conclusions Diet plays a role in the regulation of testosterone levels in women with PCOS. Further studies are needed to determine the role of diet composition in the treatment of PCOS. (ClinicalTrials.gov Identifier: NCT0455338). PMID:18331737

  17. Daily Stressors, Past Depression, and Metabolic Responses to High-Fat Meals: A Novel Path to Obesity

    PubMed Central

    Kiecolt-Glaser, Janice K.; Habash, Diane L.; Fagundes, Christopher P.; Andridge, Rebecca; Peng, Juan; Malarkey, William B.; Belury, Martha A.

    2014-01-01

    Background Depression and stress promote obesity. This study addressed the impact of daily stressors and a history of major depressive disorder (MDD) on obesity-related metabolic responses to high-fat meals. Methods This double-blind, randomized crossover study included serial assessments of resting energy expenditure (REE), fat and carbohydrate oxidation, triglycerides, cortisol, insulin and glucose before and after two high-fat meals. During two separate 9.5 hour admissions, 58 healthy women (38 breast cancer survivors and 20 demographically-similar controls), mean age 53.1 years, received either a high saturated fat meal or a high oleic sunflower oil meal. Prior day stressors were assessed by the Daily Inventory of Stressful Events and MDD history by the Structured Clinical Interview for DSM-IV. Results Greater numbers of stressors were associated with lower post-meal REE (P=.008), lower fat oxidation (P=.04), and higher insulin (P=.01), with nonsignificant effects for cortisol (P=.25) and glucose (P=.33). Women with prior MDD had higher cortisol (P=.008), and higher fat oxidation (P=.004), without significant effects for REE (P=.26), insulin (P=.25), and glucose (P=.38). Women with a depression history who also had more prior day stressors had a higher peak triglyceride response than other participants (P=.01). The only difference between meals was higher postprandial glucose following sunflower oil compared to saturated fat (P=.03). Conclusions The cumulative 6-hour difference between one prior day stressor and no stressors translates into 104 kcal, a difference that could add almost 11 pounds/year. These findings illustrate how stress and depression alter metabolic responses to high-fat meals in ways that promote obesity. PMID:25034950

  18. Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals

    PubMed Central

    2014-01-01

    Background A high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes. Methods Non-diabetic controls (n = 34) and patients with type 1 diabetes (n = 37) were given three high-caloric, fat-containing meals during one day. Blood samples were drawn at fasting (8:00) and every two hours thereafter until 18:00. Applanation tonometry was used to assess changes in the augmentation index during the investigation day. Results Three consecutive high-fat meals had only a modest effect on serum LPS-activity levels and inflammatory markers throughout the day in both groups. Of note, patients with type 1 diabetes were unable to decrease the augmentation index in response to the high-fat meals. The most profound effects of the consecutive fat loads were seen in chylomicron and HDL-metabolism. The triglyceride-rich lipoprotein remnant marker, apoB-48, was elevated in patients compared to controls both at fasting (p = 0.014) and postprandially (p = 0.035). The activities of the HDL-associated enzymes PLTP (p < 0.001), and CETP (p = 0.007) were higher and paraoxonase (PON-1) activity, an anti-oxidative enzyme bound to HDL, decreased in patients with type 1 diabetes (p = 0.027). Conclusions In response to high-fat meals, early signs of vascular dysfunction alongside accumulation of chylomicron remnants, higher augmentation index, and decreased PON-1 activity were observed in patients with type 1 diabetes. The high-fat meals had no significant impact on postprandial LPS-activity in non-diabetic subjects or patients with type 1 diabetes suggesting that metabolic endotoxemia may be more central in patients with chronic metabolic disturbances such as obesity, type 2 diabetes, or diabetic kidney disease. PMID:24959195

  19. The effect of consuming low- versus high-glycemic index meals after exercise on postprandial blood lipid response following a next-day high-fat meal

    PubMed Central

    Kaviani, M; Chilibeck, P D; Yee, P; Zello, G A

    2016-01-01

    Background/Objectives: Exercise performed shortly before (that is, within half a day of) a high-fat meal is beneficial for stimulating fat oxidation after the meal and reducing postprandial triglycerides (TG). This benefit of exercise is unfortunately negated if the after-exercise food choice to replace the calories expended during exercise is one containing high-glycemic index (HGI) carbohydrates. We determined the effect of consuming low-glycemic index (LGI) carbohydrates after an exercise session on fat oxidation and TG after a subsequent high-fat meal. Subjects/Methods: Using a randomized, counterbalanced crossover design, 23 overweight or obese individuals (body mass index ⩾25 kg m−2) performed: walking exercise (90 min) at 1800 h followed by no meal (EX); exercise followed by a meal with LGI carbohydrates (that is, lentils, EX-LGI); exercise followed by a meal with HGI carbohydrates (that is, instant potatoes, white bread, EX-HGI); and a control condition with no exercise or meal. After a 10-h overnight fast, participants were given a standardized high-fat meal. Fat oxidation was estimated before and for 6 h after this meal from respiratory gas measures and TG determined from blood samples. Results: Fat oxidation (mean±s.d.) was higher with EX (6.9±1.7 g h−1) than EX-HGI (6.3±1.6 g h−1; P=0.007) and Control (5.9±1.7 g h−1; P=0.00002), and EX-LGI (6.6±1.7 g h−1) was higher than Control (P=0.002). TG total area under the curve was 18–32% lower with EX and EX-LGI compared with control (P=0.0005 and P=0.0001, respectively) and EX-HGI (P=0.05 and P=0.021, respectively). Conclusions: A meal containing HGI carbohydrates consumed after an evening exercise session cancels the beneficial effect of exercise for stimulating fat oxidation and lowering TG after a subsequent high-fat meal, whereas consuming a post-exercise meal with LGI carbohydrates retains the positive effect of exercise. PMID:27376698

  20. A high-fat vs. a moderate-fat meal in obese boys: nutrient balance, appetite, and gastrointestinal hormone changes.

    PubMed

    Maffeis, Claudio; Surano, Maria G; Cordioli, Sira; Gasperotti, Sandra; Corradi, Massimiliano; Pinelli, Leonardo

    2010-03-01

    Meal composition is a contributing factor to fat gain. In this study, we investigated the relationship between postprandial nutrient balance, satiety, and hormone changes induced by a high-fat meal vs. a moderate-fat meal. Ten prepubertal obese boys (BMI z-score range: 1.3-3.0) were recruited. Two meals (energy: 590 kcal) were compared: (i) high-fat (HF) meal: 12% protein, 52% fat, 36% carbohydrates; (ii) moderate-fat (MF) meal: 12% protein, 27% fat, 61% carbohydrates. Pre- and postprandial (5 h) substrate oxidation (indirect calorimetry), appetite (visual analogue scale), biochemical parameters and gastrointestinal hormone concentrations were measured. Carbohydrate balance was significantly (P < 0.001) lower (31.3 (5.7) g/5 h vs. 66.9 (5.9) g/5 h) and fat balance was significantly (P < 0.001) higher (11.5 (3.3) g/5 h vs. -0.7 (2.9) g/5 h) after HF than MF meal. Appetite (area under the curve (AUC)) was significantly reduced after an MF than an HF meal (494 (55) cm.300 min vs. 595 (57) cm.300 min, P < 0.05). Postprandial triglyceride concentration (AUC) was significantly (P < 0.05) higher after an HF than an MF meal: 141.1 (30.3) mmol.300 min/l vs. 79.3 (23.8) mmol.300 min/l, respectively. Peptide YY (PYY), cholecystokinin (CCK), and ghrelin concentrations (AUC) were not significantly different after an HF and MF meal. Glucagon-like peptide-1 (GLP-1) was significantly (P < 0.05) higher after an HF than after an MF meal (72.3 (9.8) ng/ml vs. 22.7 (7.6) ng/ml, respectively), but it did not affect subjective appetite. In conclusion, an MF meal induced a better postprandial metabolic nutrient balance, triglyceride levels, and appetite suppression than an HF meal. Gastrointestinal hormones were not related to clinically assessed hunger suppression after both meals.

  1. Fruit juice drinks prevent endogenous antioxidant response to high-fat meal ingestion.

    PubMed

    Miglio, Cristiana; Peluso, Ilaria; Raguzzini, Anna; Villaño, Deborah V; Cesqui, Eleonora; Catasta, Giovina; Toti, Elisabetta; Serafini, Mauro

    2014-01-28

    High-fat meals (HFM) induce metabolic stress, leading to the activation of protective mechanisms, including inflammation and endogenous antioxidant defences. In the present study, we investigated the effects of antioxidant-rich fruit juice drinks on the endogenous antioxidant response induced by HFM. In a double-blind, cross-over design (10 d washout), fourteen overweight volunteers were randomly assigned to one of the following interventions: HFM+500 ml placebo beverage (HFM-PB, free from fruit); HFM+500 ml antioxidant beverage 1 (HFM-AB1; apple, grape, blueberry and pomegranate juices and grape skin, grape seed and green tea extracts); HFM+500 ml antioxidant beverage 2 (HFM-AB2; pineapple, black currant and plum juices). HFM-PB consumption increased the plasma levels of thiols (SH) (4 h, P< 0·001) and uric acid (UA) (2 h, P< 0·01) and total radical-trapping antioxidant parameter (TRAP) (4 h, P< 0·01). Following the consumption of drinks, UA production was significantly reduced with respect to placebo beverage consumption 8 h after HFM-AB2 consumption (P< 0·05). SH levels were reduced 0·5 (P< 0·05), 1 (P< 0·05) and 2 h (P< 0·01) after HFM-AB1 consumption and 2, 4 and 8 h (P< 0·05) after HFM-AB2 consumption. Plasma TRAP (2 h, P< 0·001) and urinary ferric reducing antioxidant power (0-8 h, P< 0·01) were increased by HFM-AB1 consumption, the drink with the highest in vitro antioxidant capacity, but not by HFM-AB2 consumption. In urine, UA levels were significantly increased from basal levels after the consumption of HFM-PB and HFM-AB2. However, neither of the beverages increased the urinary excretion of UA with respect to the placebo beverage. In conclusion, the increase in UA and SH levels induced by HFM as part of an endogenous antioxidant response to postprandial stress can be prevented by the concomitant ingestion of antioxidant-rich fruit juice drinks.

  2. Appetite regulation via exercise prior or subsequent to high-fat meal consumption.

    PubMed

    Cheng, Mary Huey-Yu; Bushnell, Darcy; Cannon, Daniel T; Kern, Mark

    2009-02-01

    This study assessed the effect of exercise timing relative to meal consumption on appetite and its hormonal regulators (i.e., PYY(3-36), ghrelin and leptin) in moderately active young men. Twelve men performed three trials in a random order: (1) meal consumption, (2) exercise 2h after a meal, (3) exercise 1h before a meal. The test meal provided 16.5 kcal kg(-1) with 70% fat, 26% carbohydrate and 4% protein. Exercise was performed at a work rate eliciting 60% of VO(2max) for 50 min. Hunger ratings and plasma leptin concentrations were measured at baseline and hours 1, 3, 5, and 7 post-meal, and plasma concentrations of ghrelin and PYY(3-36) were measured at baseline and 1, 3, and 7h after meal consumption. Exercise performed 2h after meal consumption extended the appetite suppressing effect of food intake. Furthermore, plasma PYY(3-36) concentration tended to be elevated by exercise after meal consumption. Exercise prior to food intake decreased appetite and increased plasma ghrelin concentrations. No response to timing of exercise relative to food intake on plasma leptin concentration was detected. These data indicated the timing of exercise to meal consumption may influence appetite and its hormonal regulators. Post-meal exercise may extend the suppressive effects of meal consumption on appetite.

  3. Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects.

    PubMed

    Peluso, Ilaria; Villano, Debora V; Roberts, Susan A; Cesqui, Eleonora; Raguzzini, Anna; Borges, Gina; Crozier, Alan; Catasta, Giovina; Toti, Elisabetta; Serafini, Mauro

    2014-01-01

    Postprandial stress induced by acute consumption of meals with a high fat content results in an increase of markers of cardiometabolic risk. Repeated acute dietary stress may induce a persistent low-grade inflammation, playing a role in the pathogenesis of functional gut diseases. This may cause an impairment of the complex immune response of the gastrointestinal mucosa, which results in a breakdown of oral tolerance. We investigated the effect of ingestion of a fruit-juice drink (FJD) composed by multiple fruit juice and extracts, green tea extracts and vitamin C on postprandial stress induced by a High Fat Meal (HFM) in healthy overweight subjects. Following a double blind, placebo controlled, cross-over design, 15 healthy overweight subjects were randomized to a HFM providing 1334 Kcal (55% fat, 30% carbohydrates and 15% proteins) in combination with 500 mL of a placebo drink (HFM-P) or a fruit-juice drink (HFM-FJD). Ingestion of HFM-P led to an increase in circulating levels of cholesterol, triglycerides, glucose, insulin, TNF-α and IL-6. Ingestion of HFM-FJD significantly reduced plasma levels of cholesterol and triglycerides, decreasing inflammatory response mediated by TNF-α and IL-6. Ingestion of a fruit-juice drink reduce markers of postprandial stress induced by a HFM.

  4. Does Moderate Intensity Exercise Attenuate the Postprandial Lipemic and Airway Inflammatory Response to a High-Fat Meal?

    PubMed Central

    Kurti, Stephanie P.; Rosenkranz, Sara K.; Levitt, Morton; Cull, Brooke J.; Teeman, Colby S.; Emerson, Sam R.; Harms, Craig A.

    2015-01-01

    We investigated whether an acute bout of moderate intensity exercise in the postprandial period attenuates the triglyceride and airway inflammatory response to a high-fat meal (HFM) compared to remaining inactive in the postprandial period. Seventeen (11 M/6 F) physically active (≥150 min/week of moderate-vigorous physical activity (MVPA)) subjects were randomly assigned to an exercise (EX; 60% VO2peak) or sedentary (CON) condition after a HFM (10 kcal/kg, 63% fat). Blood analytes and airway inflammation via exhaled nitric oxide (eNO) were measured at baseline, and 2 and 4 hours after HFM. Airway inflammation was assessed with induced sputum and cell differentials at baseline and 4 hours after HFM. Triglycerides doubled in the postprandial period (~113 ± 18%, P < 0.05), but the increase did not differ between EX and CON. Percentage of neutrophils was increased 4 hours after HFM (~17%), but the increase did not differ between EX and CON. Exhaled nitric oxide changed nonlinearly from baseline to 2 and 4 hours after HFM (P < 0.05,  η2 = 0.36). Our findings suggest that, in active individuals, an acute bout of moderate intensity exercise does not attenuate the triglyceride or airway inflammatory response to a high-fat meal. PMID:26000301

  5. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet.

    PubMed

    Gao, Xiang; Liu, Xiaofang; Xu, Jie; Xue, Changhu; Xue, Yong; Wang, Yuming

    2014-10-01

    Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine (TMA) and is present in many aquatic foods. Here, we investigated the effects of TMAO on glucose tolerance in high fat diet (HFD)-fed mice. Male C57BL/6 mice were randomly assigned to the control, high fat (HF), and TMAO groups. The HF group was fed a diet containing 25% fat, and the TMAO group was fed the HFD plus 0.2% TMAO for 4 weeks. After 3 weeks of feeding, oral glucose tolerance tests were performed. Dietary TMAO increased fasting insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR) and exacerbated the impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the insulin signal pathway, glycogen synthesis, gluconeogenesis and glucose transport in liver. mRNA levels of the pro-inflammatory cytokine MCP-1 increased significantly and of the anti-inflammatory cytokine IL-10 greatly decreased in adipose tissue. Our results suggest that dietary TMAO exacerbates impaired glucose tolerance, obstructs the hepatic insulin signaling pathway, and causes adipose tissue inflammation in mice fed a high fat diet.

  6. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF.

    PubMed

    Moy, Gregory A; McNay, Ewan C

    2013-01-17

    Obesity, high-fat diets, and subsequent type 2 diabetes (T2DM) are associated with cognitive impairment. Moreover, T2DM increases the risk of Alzheimer's disease (AD) and leads to abnormal elevation of brain beta-amyloid levels, one of the hallmarks of AD. The psychoactive alkaloid caffeine has been shown to have therapeutic potential in AD but the central impact of caffeine has not been well-studied in the context of a high-fat diet. Here we investigated the impact of caffeine administration on metabolism and cognitive performance, both in control rats and in rats placed on a high-fat diet. The effects of caffeine were significant: caffeine both (i) prevented the weight-gain associated with the high-fat diet and (ii) prevented cognitive impairment. Caffeine did not alter hippocampal metabolism or insulin signaling, likely because the high-fat-fed animals did not develop full-blown diabetes; however, caffeine did prevent or reverse a decrease in hippocampal brain-derived neurotrophic factor (BDNF) seen in high-fat-fed animals. These data confirm that caffeine may serve as a neuroprotective agent against cognitive impairment caused by obesity and/or a high-fat diet. Increased hippocampal BDNF following caffeine administration could explain, at least in part, the effects of caffeine on cognition and metabolism.

  7. Postprandial Effect of a High-Fat Meal on Endotoxemia in Arab Women with and without Insulin-Resistance-Related Diseases.

    PubMed

    Al-Disi, Dara A; Al-Daghri, Nasser M; Khan, Nasiruddin; Alfadda, Assim A; Sallam, Reem M; Alsaif, Mohammed; Sabico, Shaun; Tripathi, Gyanendra; McTernan, Philip G

    2015-08-04

    This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12-14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.

  8. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variant...

  9. Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.

    PubMed

    Kaczmarczyk, Melissa M; Machaj, Agnieszka S; Chiu, Gabriel S; Lawson, Marcus A; Gainey, Stephen J; York, Jason M; Meling, Daryl D; Martin, Stephen A; Kwakwa, Kristin A; Newman, Andrew F; Woods, Jeffrey A; Kelley, Keith W; Wang, Yanyan; Miller, Michael J; Freund, Gregory G

    2013-09-01

    The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD). After 1wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1α, IL-1β, TNF-α and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD.

  10. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA.

    PubMed

    Rontoyanni, Victoria G; Hall, Wendy L; Pombo-Rodrigues, Sonia; Appleton, Amber; Chung, Roxanna; Sanders, Thomas A B

    2012-08-01

    Long-chain n-3 PUFA can lower blood pressure (BP) but their acute effects on cardiac output, BP and systemic vascular resistance (SVR) in response to dynamic exercise are uncertain. We compared the effects of high-fat meals rich in EPA (20 : 5n-3), DHA (22 : 6n-3) or oleic acid (control) on cardiac output, BP and SVR in response to exercise stress testing. High-fat meals (50 g fat) containing high-oleic sunflower oil enriched with 4·7 g of either EPA or DHA v. control (high-oleic sunflower oil only) were fed to twenty-two healthy males using a randomised cross-over design. Resting measurements of cardiac output, heart rate and BP were made before and hourly over 5 h following the meal. A standardised 12 min exercise test was then conducted with further measurements made during and post-exercise. Blood samples were collected at fasting, 5 h postprandially and immediately post-exercise for the analysis of lipid, glucose and 8-isoprostane-F2α (8-iso-PGF2α). Plasma concentrations of EPA and DHA increased by 0·22 mmol/l 5 h following the EPA and DHA meals, respectively, compared with the control (P < 0·001). Resting cardiac output and 8-iso-PGF2α increased similarly following all meals and there were no significant differences in cardiac output during exercise between the meals. SVR was lower at 5 h and during exercise following the DHA but not EPA meal, compared with the control meal, by 4·9 % (95 % CI 1·3, 8·4; P < 0·01). Meals containing DHA appear to differ from EPA with regard to their effects on cardiovascular haemodynamics during exercise.

  11. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

  12. Effect of exercise intensity on postprandial lipemia, markers of oxidative stress, and endothelial function after a high-fat meal.

    PubMed

    Lopes Krüger, Renata; Costa Teixeira, Bruno; Boufleur Farinha, Juliano; Cauduro Oliveira Macedo, Rodrigo; Pinto Boeno, Francesco; Rech, Anderson; Lopez, Pedro; Silveira Pinto, Ronei; Reischak-Oliveira, Alvaro

    2016-12-01

    The aim of this study was to compare the effects of 2 different exercise intensities on postprandial lipemia, oxidative stress markers, and endothelial function after a high-fat meal (HFM). Eleven young men completed 2-day trials in 3 conditions: rest, moderate-intensity exercise (MI-Exercise) and heavy-intensity exercise (HI-Exercise). Subjects performed an exercise bout or no exercise (Rest) on the evening of day 1. On the morning of day 2, an HFM was provided. Blood was sampled at fasting (0 h) and every hour from 1 to 5 h during the postprandial period for triacylglycerol (TAG), thiobarbituric acid reactive substance (TBARS), and nitrite/nitrate (NOx) concentrations. Flow-mediated dilatation (FMD) was also analyzed. TAG concentrations were reduced in exercise conditions compared with Rest during the postprandial period (P < 0.004). TAG incremental area under the curve (iAUC) was smaller after HI-Exercise compared with Rest (P = 0.012). TBARS concentrations were reduced in MI-Exercise compared with Rest (P < 0.041). FMD was higher in exercise conditions than Rest at 0 h (P < 0.02) and NOx concentrations were enhanced in MI-Exercise compared with Rest at 0 h (P < 0.01). These results suggest that acute exercise can reduce lipemia after an HFM. However, HI-Exercise showed to be more effective in reducing iAUC TAG, which might suggest higher protection against postprandial TAG enhancement. Conversely, MI-Exercise can be beneficial to attenuate the susceptibility of oxidative damage induced by an HFM and to increase endothelial function in the fasted state compared with Rest.

  13. Impaired Lipid and Glucose Homeostasis in Hexabromocyclododecane-Exposed Mice Fed a High-Fat Diet

    PubMed Central

    Koike, Eiko; Win-Shwe, Tin-Tin; Yamamoto, Megumi; Takano, Hirohisa

    2014-01-01

    Background: Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear. Objectives: We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue. Results: In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice. Conclusions: Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity. Citation: Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health

  14. Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?

    PubMed Central

    Medei, Emiliano; Lima-Leopoldo, Ana Paula; Pereira-Junior, Pedro Paulo; Leopoldo, André Soares; Campos, Dijon Henrique Salomé; Raimundo, Juliana Montani; Sudo, Roberto Takashi; Zapata-Sudo, Gisele; Bruder-Nascimento, Thiago; Cordellini, Sandra; Nascimento, José Hamilton Matheus; Cicogna, Antonio Carlos

    2010-01-01

    BACKGROUND: Dyslipidemia results from consumption of a diet rich in saturated fatty acids and is usually associated with cardiovascular disease. A diet rich in unsaturated fatty acids is usually associated with improved cardiovascular condition. OBJECTIVE: To investigate whether a high-fat diet rich in unsaturated fatty acids (U-HFD) – in which fatty acid represents approximately 45% of the total calories – impairs the cardiovascular system. METHODS: Male, 30-day-old Wistar rats were fed a standard (control) diet or a U-HFD containing 83% unsaturated fatty acid for 19 weeks. The in vivo electrocardiogram, the spectral analysis of heart rate variability, and the vascular reactivity responses to phenylephrine, acetylcholine, noradrenaline and prazosin in aortic ring preparations were analyzed to assess the cardiovascular parameters. RESULTS: After 19 weeks, the U-HFD rats had increased total body fat, baseline glucose levels and feed efficiency compared with control rats. However, the final body weight, systolic blood pressure, area under the curve for glucose, calorie intake and heart weight/final body weight ratio were similar between the groups. In addition, both groups demonstrated no alteration in the electrocardiogram or cardiac sympathetic parameters. There was no difference in the responses to acetylcholine or the maximal contractile response of the thoracic aorta to phenylephrine between groups, but the concentration necessary to produce 50% of maximal response showed a decrease in the sensitivity to phenylephrine in U-HFD rats. The cumulative concentration-effect curve for noradrenaline in the presence of prazosin was shifted similarly in both groups. CONCLUSIONS: The present work shows that U-HFD did not impair the cardiovascular parameters analyzed. PMID:21165364

  15. A high fat diet-induced impaired glucose metabolism in mice with targeted deletion of calpain in osteoblasts.

    PubMed

    Kashiwagi, Aki; Fein, Mikaela J; Shimada, Masako

    2011-06-03

    The ubiquitously expressed Calpains 1 and 2 belong to a family of calcium-dependent intracellular cysteine proteases. Both calpains are heterodimers consisting of a large subunit and a small regulatory subunit encoded by the gene Capns1. To investigate a role for the calpain small subunit in cells of the osteoblast lineage in vivo, we previously generated osteoblast-specific Capns1 knockout mice and characterized their bone phenotype. In this study, we further examined effects of low calcium and high fat diets on their bone, fat, and glucose homeostasis. Osteoblast-specific Capns1 knockout mice showed significantly reduced serum levels of total and uncarboxylated osteocalcin, and this was presumably due to their impaired bone formation and bone resorption. The reduced bone resorptive function of the mutant mice was also significant under a low calcium diet. Thus, these results suggest that reduced uncarboxylated osteocalcin levels of mutant mice were, at least in part, due to their osteoporotic bone with impaired bone resorptive function. Interestingly, unlike osteocalcin knockout mice, mutant mice on a normal chow diet were leaner than control littermates; this was likely due to their reduced food intake and overall lower energy homeostasis. To test this hypothesis, we next provided mutant mice with a high fat diet and further examined an effect of their reduced uncarboxylated osteocalcin levels on body composition and glucose metabolism. The average mean body weight of mutant mice became indistinguishable with that of controls after 2 weeks on a high fat diet, and continued to show an upward trend, at least, up to 6weeks. Moreover, mutant mice on a high fat diet exhibited a significant increase in serum levels of leptin and resistin, adipocyte-specific adipokines, and developed impaired glucose tolerance. Collectively, mice with osteoporosis and reduced bone resorptive function showed reduced serum uncarboxylated osteocalcin levels and were susceptible to

  16. High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.

    PubMed

    Liu, Zhigang; Patil, Ishan Y; Jiang, Tianyi; Sancheti, Harsh; Walsh, John P; Stiles, Bangyan L; Yin, Fei; Cadenas, Enrique

    2015-01-01

    High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts

  17. High fat diet impairs the function of glucagon-like peptide-1 producing L-cells

    PubMed Central

    Richards, Paul; Pais, Ramona; Habib, Abdella M.; Brighton, Cheryl A.; Yeo, Giles S.H.; Reimann, Frank; Gribble, Fiona M.

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. Methods Transgenic mouse models were utilized in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. Results Two weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L-cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. Conclusion Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post-prandial signaling, which could impact on insulin secretion and satiety. PMID:26145551

  18. Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults.

    PubMed

    Volek, Jeff S; Judelson, Daniel A; Silvestre, Ricardo; Yamamoto, Linda M; Spiering, Barry A; Hatfield, Disa L; Vingren, Jakob L; Quann, Erin E; Anderson, Jeffrey M; Maresh, Carl M; Kraemer, William J

    2008-11-15

    Because carnitine has been shown to decrease oxidative stress and improve endothelial cell functioning, we examined the effects of carnitine supplementation on postprandial flow-mediated dilation (FMD) and circulating biomarkers of inflammation and oxidative stress after a high-fat meal. A randomized, double-blind, placebo-controlled, crossover study design was used. Thirty men and women (age 30 +/- 8 year, body mass 72.9 +/- 17.1 kg, body fat 13.0 +/- 6.4%) participated in 2 vascular testing days, each preceded by 3 weeks of supplementation with either 2 g/day of L-Carnitine (L-Carnitine L-Tartrate) or placebo with a 3- to 5-week washout period between trials. Brachial artery FMD in response to 5 minutes of upper arm occlusion and circulating markers of oxidative stress and inflammation were measured in the fasting state and after a standardized high-fat meal. After 3 weeks of supplementation, peak FMD in the fasting state was similar between the carnitine and placebo trials, averaging 6.6%. Peak FMD during the postprandial period decreased to 5.8% at 1.5 hours during placebo and increased to 7.7% during the carnitine trial (n = 30: p = 0.043 for supplement by time interaction effect). This improvement in postprandial vascular function was most dramatic in subjects who showed a decrease in peak FMD in response to the meal (n = 15: p = 0.003 for supplement by time interaction effect). There was a significant increase in postprandial lipemia and plasma interleukin-6 but no effect of supplementation. There were no significant postprandial changes or supplement effects for plasma tumor necrosis factor-alpha and malondialdehyde. In conclusion, consistent with other work showing a beneficial effect of carnitine on vascular function, these findings indicate that carnitine supplementation in healthy individuals improves postprandial FMD after a high-fat meal.

  19. Maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction

    PubMed Central

    Mdaki, Kennedy S.; Larsen, Tricia D.; Wachal, Angela L.; Schimelpfenig, Michelle D.; Weaver, Lucinda J.; Dooyema, Samuel D. R.; Louwagie, Eli J.

    2016-01-01

    Offspring of diabetic pregnancies are at risk of cardiovascular disease at birth and throughout life, purportedly through fuel-mediated influences on the developing heart. Preventative measures focus on glycemic control, but the contribution of additional offenders, including lipids, is not understood. Cellular bioenergetics can be influenced by both diabetes and hyperlipidemia and play a pivotal role in the pathophysiology of adult cardiovascular disease. This study investigated whether a maternal high-fat diet, independently or additively with diabetes, could impair fuel metabolism, mitochondrial function, and cardiac physiology in the developing offspring's heart. Sprague-Dawley rats fed a control or high-fat diet were administered placebo or streptozotocin to induce diabetes during pregnancy and then delivered offspring from four groups: control, diabetes exposed, diet exposed, and combination exposed. Cardiac function, cellular bioenergetics (mitochondrial stress test, glycolytic stress test, and palmitate oxidation assay), lipid peroxidation, mitochondrial histology, and copy number were determined. Diabetes-exposed offspring had impaired glycolytic and respiratory capacity and a reduced proton leak. High-fat diet-exposed offspring had increased mitochondrial copy number, increased lipid peroxidation, and evidence of mitochondrial dysfunction. Combination-exposed pups were most severely affected and demonstrated cardiac lipid droplet accumulation and diastolic/systolic cardiac dysfunction that mimics that of adult diabetic cardiomyopathy. This study is the first to demonstrate that a maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancies through metabolic stress and serves as a critical step in understanding the role of cellular bioenergetics in developmentally programmed cardiac disease. PMID:26801311

  20. Effect of Low- and High-Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First-in-Class BCL-2 Inhibitor.

    PubMed

    Salem, Ahmed Hamed; Agarwal, Suresh K; Dunbar, Martin; Nuthalapati, Silpa; Chien, David; Freise, Kevin J; Wong, Shekman L

    2016-11-01

    Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax in healthy subjects: (1) a bioequivalence study to compare the bioavailability of the film-coated tablet with that of an earlier uncoated tablet and (2) a food effect study to evaluate the effect of food on venetoclax pharmacokinetics. Both studies were open-label, single-dose, crossover studies. In the bioequivalence study, 15 subjects received a single dose of venetoclax 50 mg under nonfasting conditions, in each of 2 periods; one period used the uncoated tablet, and the other used the film-coated tablet. In the food effect study, 24 subjects received a single dose of venetoclax film-coated 100-mg tablet under fasting conditions, after a low-fat breakfast or after a high-fat breakfast in different periods. The venetoclax film-coated tablet was bioequivalent to the uncoated tablet, which indicates that the film coating does not affect bioavailability. The median Tmax of venetoclax was delayed by about 2 hours when administered with food. Compared with fasting conditions, Cmax and AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased Cmax and AUC by approximately 50% relative to low-fat meals. The mean terminal half-life was comparable between the high-fat meal and fasting conditions (19.1 versus 16.1 hours). Based on these results and the venetoclax exposure-response profile, venetoclax should be administered with food and without specific recommendations for fat content to ensure adequate and consistent bioavailability.

  1. IRF-1 and miRNA126 modulate inflammatory VCAM-1 expression in response to a high fat meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rationale: High-fat diets accompanied by hypertriglyceridemia increase an individual’s risk for developing atherosclerosis. An early event in this process is monocyte recruitment through binding to VCAM-1 on inflamed arterial endothelium. Diets high in polyunsaturated fatty acids (PUFAs) may provide...

  2. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    PubMed Central

    Underwood, Erica L.; Thompson, Lucien T.

    2016-01-01

    While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID:26819773

  3. Measuring the short-term substrate utilization response to high-carbohydrate and high-fat meals in the whole-body indirect calorimeter.

    PubMed

    Gribok, Andrei; Leger, Jayme L; Stevens, Michelle; Hoyt, Reed; Buller, Mark; Rumpler, William

    2016-06-01

    The paper demonstrates that minute-to-minute metabolic response to meals with different macronutrient content can be measured and discerned in the whole-body indirect calorimeter. The ability to discriminate between high-carbohydrate and high-fat meals is achieved by applying a modified regularization technique with additional constraints imposed on oxygen consumption rate. These additional constraints reduce the differences in accuracy between the oxygen and carbon dioxide analyzers. The modified technique was applied to 63 calorimeter sessions that were each 24 h long. The data were collected from 16 healthy volunteers (eight males, eight females, aged 22-35 years). Each volunteer performed four 24-h long calorimeter sessions. At each session, they received one of four treatment combinations involving exercise (high or low intensity) and diet (a high-fat or high-carbohydrate shake for lunch). One volunteer did not complete all four assignments, which brought the total number of sessions to 63 instead of 64. During the 24-h stay in the calorimeter, subjects wore a continuous glucose monitoring system, which was used as a benchmark for subject's postprandial glycemic response. The minute-by-minute respiratory exchange ratio (RER) data showed excellent agreement with concurrent subcutaneous glucose concentrations in postprandial state. The averaged minute-to-minute RER response to the high-carbohydrate shake was significantly different from the response to high-fat shake. Also, postprandial RER slopes were significantly different for two dietary treatments. The results show that whole-body respiration calorimeters can be utilized as tools to study short-term kinetics of substrate oxidation in humans.

  4. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice.

    PubMed

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD.

  5. Chronic High Fat Diet Consumption Impairs Metabolic Health of Male Mice

    PubMed Central

    Morselli, Eugenia; Criollo, Alfredo; Rodriguez-Navas, Carlos; Clegg, Deborah J.

    2015-01-01

    We show that chronic high fat diet (HFD) feeding affects the hypothalamus of male but not female mice. In our study we demonstrate that palmitic acid and sphingolipids accumulate in the central nervous system of HFD-fed males. Additionally, we show that HFD-feeding reduces proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) thus reducing estrogen receptor α (ERα) and driving hypothalamic inflammation in male but not female mice. Hypothalamic inflammation correlates with markers of metabolic dysregulation as indicated by dysregulation in glucose intolerance and myocardial function. Lastly, we demonstrate that there are blockages in mitophagy and lipophagy in hypothalamic tissues in males. Our data suggest there is a sexually dimorphic response to chronic HDF exposure, females; despite gaining the same amount of body weight following HFD-feeding, appear to be protected from the adverse metabolic effects of the HFD. PMID:26046098

  6. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    PubMed Central

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  7. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

    PubMed

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2013-01-15

    Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory.

  8. Evidence of impairment of normal inflammatory reaction by a high-fat diet.

    PubMed

    Laflamme, C; Bertheau-Mailhot, G; Giambelluca, M S; Cloutier, N; Boilard, E; Pouliot, M

    2014-04-01

    The murine dorsal air pouch model is a valuable tool for studying acute peripheral inflammatory reactions. We used this model to study the effect of diet on the onset of acute inflammation. Mice were fed a normal or a high-fat diet (HFD) for 5 weeks. Air pouches were raised and injected with non-stimulating (saline) or stimulating solution (saline containing lipopolysaccharides). After 4 h, leukocytes in the pouch fluid were enumerated, sorted and their viability measured. Cytokine/chemokine levels in the cell-free fluid were measured using a cytometric bead assay. Gene expression level was measured in leukocytes and in lining tissues using comparative real-time PCR. Leukocyte migration and cytokine/chemokine secretion were decreased substantially in mice fed the HFD. In contrast, leptin levels were elevated. Gene expression profiles in leukocytes recovered from the pouch and in the pouch-lining tissue (believed to have an important role in the initiation of granulocyte recruitment) were depressed. Genes encoding CC and CXC family chemokines were among the most negatively affected. These results suggest that a HFD can alter peripheral tissue activation as well as leukocyte recruitment and response, thereby affecting the development of an effective local immune response, which could have deleterious consequences.

  9. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice

    PubMed Central

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-01-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  10. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice.

    PubMed

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-06-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment.

  11. Bile sequestration potential of an edible mineral (clinoptilolite) under simulated digestion of a high-fat meal: an in vitro investigation.

    PubMed

    Kristo, Aleksandra S; Tzanidaki, Garyfallia; Lygeros, Andreas; Sikalidis, Angelos K

    2015-12-01

    Bile, important for cholesterol homeostasis, is a potential target of hypercholesterolemia management. Bile sequestration by orally administered resins, while mostly effective in reducing blood cholesterol, presents several side effects and disadvantages. Thus, widely available natural edible minerals such as clinoptilolite with adsorptive properties offer an alternative for bile sequestration. In an experimental setting mimicking the physiological conditions of digestion/absorption (pH, temperature, and retention times) with a series of assessment methods, scanning electron microscopy-energy dispersion X-ray analysis (SEM-EDX), X-ray diffraction (XRD), Fourier transform infrared analysis (FT-IR), thermogravimetric differential thermal analysis (TG-DTA), and molecular docking modeling, the ability of natural unmodified clinoptilolite to retain bile, while mixed with a simulated high-fat meal, was investigated. Our results demonstrate that clinoptilolite sequesters bile via adsorption of macromicelles at 75.4% efficiency, when the former is administered at a reasonable dose of 4% (w/w) of a meal's weight. This work provides the possibility of clinoptilolite utilization as a bile-sequestering/cholesterol-reducing agent.

  12. Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: the role of oxidative stress.

    PubMed

    Alzoubi, Karem H; Khabour, Omar F; Salah, Heba A; Hasan, Zuheir

    2013-07-02

    Memory and learning are impaired by imbalanced diet consumption. High-fat high-carbohydrate diet (HFCD) induces oxidative stress, which results in neuronal damage and interference with synaptic transmission; hence, a decline in cognitive function. Vitamin E is a fat soluble antioxidant that is believed to have positive effects on learning and memory. In this study, we tested the hypothesis that chronic administration of vitamin E prevents learning and memory impairment induced by HFCD. In addition, possible molecular targets for HFCD, and vitamin E that lead to cognitive effects were examined. Vitamin E and/or HFCD were concurrently administered to animals for 6 weeks. Thereafter, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). Additionally, brain derived neurotrophic factor (BDNF) level and antioxidant markers were assessed in the hippocampus. The results of this project revealed that HFCD impairs both short-term and long-term memories (p<0.05). The administration of vitamin E prevented the memory impairment induced by HFCD consumption (p<0.05). The consumption of HFCD reduced activities of hippocampal superoxide dismutase (SOD) and catalase (p<0.05); whereas the levels of thiobarbituric acid reactive substances (TBARS) and oxidized glutathione (GSSG) were elevated (p<0.05). The administration of vitamin E normalized the effect of HFCD on the oxidative stress markers. None of the treatments induced changes in the levels of BDNF or glutathione peroxidase (GPx). In conclusion, HFCD induces memory impairment, and the administration of vitamin E prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus.

  13. No difference in acute effects of supplemental v. dietary calcium on blood pressure and microvascular function in obese women challenged with a high-fat meal: a cross-over randomised study.

    PubMed

    Ferreira, Thaís da Silva; Leal, Priscila Mansur; Antunes, Vanessa Parada; Sanjuliani, Antonio Felipe; Klein, Márcia Regina Simas Torres

    2016-11-01

    Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

  14. High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

    PubMed

    Salimi, M; Zardooz, H; Khodagholi, F; Rostamkhani, F; Shaerzadeh, F

    2016-10-01

    This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

  15. Thermosensing mechanisms and their impairment by high-fat diet in orexin neurons.

    PubMed

    Belanger-Willoughby, N; Linehan, V; Hirasawa, M

    2016-06-02

    In homeotherms, the hypothalamus controls thermoregulatory and adaptive mechanisms in energy balance, sleep-wake and locomotor activity to maintain optimal body temperature. Orexin neurons may be involved in these functions as they promote thermogenesis, food intake and behavioral arousal, and are sensitive to temperature and metabolic status. How thermal and energy balance signals are integrated in these neurons is unknown. Thus, we investigated the cellular mechanisms of thermosensing in orexin neurons and their response to a change in energy status using whole-cell patch clamp on rat brain slices. We found that warming induced an increase in miniature excitatory postsynaptic current (EPSC) frequency, which was blocked by the transient receptor potential vanilloid-1 (TRPV1) receptor antagonist AMG9810 and mimicked by its agonist capsaicin, suggesting that the synaptic effect is mediated by heat-sensitive TRPV1 channels. Furthermore, warming inhibits orexin neurons by activating ATP-sensitive potassium (KATP) channels, an effect regulated by uncoupling protein 2 (UCP2), as the UCP2 inhibitor genipin abolished this response. These properties are unique to orexin neurons in the lateral hypothalamus, as neighboring melanin-concentrating hormone neurons showed no response to warming within the physiological temperature range. Interestingly, in rats fed with western diet for 1 or 11weeks, orexin neurons had impaired synaptic and KATP response to warming. In summary, this study reveals several mechanisms underlying thermosensing in orexin neurons and their attenuation by western diet. Overeating induced by western diet may in part be due to impaired orexin thermosensing, as post-prandial thermogenesis may promote satiety and lethargy by inhibiting orexin neurons.

  16. Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice

    PubMed Central

    Liang, Xingwei; Yang, Qiyuan; Zhang, Lupei; Maricelli, Joseph W; Rodgers, Buel D.; Zhu, Mei-Jun; Du, Min

    2016-01-01

    Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates energy via heat generation, mitigating obesity and diabetes. The lactation stage is a manageable period for improving the health of offspring of obese mothers, but the impact of maternal HFD during lactation on offspring BAT function is unknown. To determine, female mice were fed either a control or HFD during lactation. At weaning, HFD offspring gained more body weight and had greater body fat mass compared to the control, and these differences maintained into adulthood, which correlated with glucose intolerance and insulin resistance in HFD offspring. Adaptive thermogenesis of BAT was impaired in HFD offspring at weaning. In adulthood, HFD offspring BAT had lower Ucp1 expression and thermogenic activity. Mechanistically, maternal HFD feeding during lactation elevated peripheral serotonin, which decreased the sensitivity of BAT to sympathetic β3-adrenergic signaling. Importantly, early postnatal metformin administration decreased serotonin concentration and ameliorated the impairment of offspring BAT due to maternal HFD. Our data suggest that attenuation of BAT thermogenic function may be a key mechanism linking maternal HFD during lactation to persisted metabolic disorder in the offspring. PMID:27686741

  17. Lack of Effects of a Single High-Fat Meal Enriched with Vegetable n-3 or a Combination of Vegetable and Marine n-3 Fatty Acids on Intestinal Peptide Release and Adipokines in Healthy Female Subjects

    PubMed Central

    Narverud, Ingunn; Myhrstad, Mari C. W.; Herzig, Karl-Heinz; Karhu, Toni; Dahl, Tuva B.; Halvorsen, Bente; Ulven, Stine M.; Holven, Kirsten B.

    2016-01-01

    Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3) fatty acids (FAs) from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 FAs with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil, and a combination of linseed and cod liver oil. The test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analyzed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin, which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 FAs from different origin stimulates intestinal peptide release without any difference between the different fat compositions. PMID:27630989

  18. GENOME-WIDE ASSOCIATION STUDY OF TRIGLYCERIDE RESPONSE TO A HIGH-FAT MEAL AMONG PARTICIPANTS OF THE NHLBI GENETICS OF LIPID LOWERING DRUGS AND DIET NETWORK (GOLDN)

    PubMed Central

    Wojczynski, M.K.; Parnel, L.D.; Pollin, T.I.; Lai, C.Q.; Feitosa, M.F.; O’Connell, J.R.; Frazier-Wood, A.C.; Gibson, Q.; Aslibekyan, S.; Ryan, K.A.; Province, M.A.; Tiwari, H.K.; Ordovas, J.M.; Shuldiner, A.R.; Arnett, D.K.; Borecki, I.B.

    2015-01-01

    Objective The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Methods The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n=843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n=1,715) was performed on the top SNPs from GOLDN. Results GOLDN revealed 111 suggestive (p<1E-05) associations, with two SNPs meeting GWA significance level (p<5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p=1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p=1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. Conclusion This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics. PMID:26256467

  19. Effects of a high fat meal matrix and protein complexation on the bioaccessibility of blueberry anthocyanins using the TNO gastrointestinal model (TIM-1).

    PubMed

    Ribnicky, David M; Roopchand, Diana E; Oren, Andrew; Grace, Mary; Poulev, Alexander; Lila, Mary Ann; Havenaar, Robert; Raskin, Ilya

    2014-01-01

    The TNO intestinal model (TIM-1) of the human upper gastrointestinal tract was used to compare intestinal absorption/bioaccessibility of blueberry anthocyanins under different digestive conditions. Blueberry polyphenol-rich extract was delivered to TIM-1 in the absence or presence of a high-fat meal. HPLC analysis of seventeen anthocyanins showed that delphinidin-3-glucoside, delphinidin-3-galactoside, delphinidin-3-arabinoside and petunidin-3-arabinoside were twice as bioaccessible in fed state, whilst delphinidin-3-(6″-acetoyl)-glucoside and malvidin-3-arabinoside were twice as bioaccessible under fasted conditions, suggesting lipid-rich matrices selectively effect anthocyanin bioaccessibility. TIM-1 was fed blueberry juice (BBJ) or blueberry polyphenol-enriched defatted soybean flour (BB-DSF) containing equivalent amounts of free or DSF-sorbed anthocyanins, respectively. Anthocyanin bioaccessibility from BB-DSF (36.0±10.4) was numerically, but not significantly, greater than that from BBJ (26.3±10.3). Ileal efflux samples collected after digestion of BB-DSF contained 2.8-fold more anthocyanins than same from BBJ, suggesting that protein-rich DSF protects anthocyanins during transit through upper digestive tract for subsequent colonic delivery/metabolism.

  20. Mice lacking C1q are protected from high fat diet-induced hepatic insulin resistance and impaired glucose homeostasis.

    PubMed

    Hillian, Antoinette D; McMullen, Megan R; Sebastian, Becky M; Roychowdhury, Sanjoy; Rowchowdhury, Sanjoy; Kashyap, Sangeeta R; Schauer, Philip R; Kirwan, John P; Feldstein, Ariel E; Nagy, Laura E

    2013-08-02

    Complement activation is implicated in the development of obesity and insulin resistance, and loss of signaling by the anaphylatoxin C3a prevents obesity-induced insulin resistance in mice. Here we have identified C1q in the classical pathway as required for activation of complement in response to high fat diets. After 8 weeks of high fat diet, wild-type mice became obese and developed glucose intolerance. This was associated with increased apoptotic cell death and accumulation of complement activation products (C3b/iC3b/C3c) in liver and adipose tissue. Previous studies have shown that high fat diet-induced apoptosis is dependent on Bid; here we report that Bid-mediated apoptosis was required for complement activation in adipose and liver. Although C1qa deficiency had no effect on high fat diet-induced apoptosis, accumulation of complement activation products and the metabolic complications of high fat diet-induced obesity were dependent on C1q. When wild-type mice were fed a high fat diet for only 3 days, hepatic insulin resistance was associated with the accumulation of C3b/iC3b/C3c in the liver. Mice deficient in C3a receptor were protected against this early high fat diet-induced hepatic insulin resistance, whereas mice deficient in the negative complement regulator CD55/DAF were more sensitive to the high fat diet. C1qa(-/-) mice were also protected from high fat diet-induced hepatic insulin resistance and complement activation. Evidence of complement activation was also detected in adipose tissue of obese women compared with lean women. Together, these studies reveal an important role for C1q in the classical pathway of complement activation in the development of high fat diet-induced insulin resistance.

  1. A high-fat diet impairs reproduction by decreasing the IL1β level in mice treated at immature stage.

    PubMed

    Zhang, Jie; Li, Kai; Yuan, Miao; Zhang, Jie; Huang, Guizen; Ao, Jie; Tan, Haoze; Li, Yanyan; Gong, Di; Li, Jun; Kang, Lei; An, Nini; Li, Fei; Lin, Ping; Huang, Lugang

    2017-04-03

    Obesity causes low-grade inflammation that is involved in male infertility. Interleukin 1 beta (IL1β) plays an important role in this process. A high-fat diet (HFD) is the most common cause of obesity. However, the effect of a HFD on IL1β and its consequence in reproduction remain unclear. We established a HFD model in mice treated at immature stage (mice-TIS) and mice treated at mature stage (mice-TMS). Surprisingly, we found that a HFD decreased IL1β levels and was accompanied by an increase in testosterone in mice-TIS, while the reverse results were observed in mice-TMS. In addition, a HFD caused a reduction in testis macrophages and in the expression of inflammasome-related genes and proteins in mice-TIS. Furthermore, we found that IL1β inhibited testosterone secretion through down-regulating the gene expression of P450SCC and P450c17. However, the influence on mice-TIS that were induced by a HFD was recovered by stopping the HFD. In this study, we are the first to report that a HFD impairs the reproductive system by decreasing IL1β and enhancing testosterone levels in mice-TIS, which are different from the effects in mice-TMS. This provides new ideas for the treatment of obesity-induced infertility.

  2. Ameliorating effect and potential mechanism of Rehmannia glutinosa oligosaccharides on the impaired glucose metabolism in chronic stress rats fed with high-fat diet.

    PubMed

    Zhang, Ruxue; Zhou, Jun; Li, Maoxing; Ma, Haigang; Qiu, Jianguo; Luo, Xiaohong; Jia, Zhengping

    2014-04-15

    The aim of this study was to determine whether the Rehmannia glutinosa oligosaccharides (ROS) ameliorate the impaired glucose metabolism and the potential mechanism in chronic stress rats fed with high-fat diet. The rats were fed by a high-fat diet and simultaneously stimulated by chronic stress over 5 weeks. Body weight, fasting plasma glucose, intraperitoneal glucose tolerance test (IPGTT), plasma lipids, gluconeogenesis test (GGT), glycogen content, and corticosterone, insulin and leptin levels were measured. The results showed that ROS administration (100, 200 mg/kg, i.g.) for 5 weeks exerted the effects of increasing the organ weights of thymus and spleen, lowering the fasting plasma glucose level, improving impaired glucose tolerance, increasing the contents of liver and muscle glycogen, decreasing the gluconeogenesis ability, plasma-free fatty acid's level, as well as plasma triglyceride and total cholesterol levels in chronic stress and high-fat fed rats, especially in the group of 200mg/kg; while the plasma corticosterone level was decreased, and plasma leptin level was increased. These results suggest that ROS exert an ameliorating effect of impaired glucose metabolism in chronic stress rats fed with high-fat diet, and the potential mechanism may be mediated through rebuilding the glucose homeostasis in the neuroendocrine immuno-modulation (NIM) network through multilinks and multitargets.

  3. A high-fat diet impairs learning that is dependent on the dorsal hippocampus but spares other forms of learning.

    PubMed

    Stouffer, Eric M; Warninger, Elizabeth E; Michener, Paige N

    2015-12-01

    Two experiments were conducted to evaluate the effects of a high-fat diet (HFD) on two tasks that were either dependent on the dorsal hippocampus (DH) or independent of the DH. A total of 80 adult male Sprague Dawley rats were administered either a lard-based HFD (60% of calories from fat) or a control diet (10% of calories from fat) for 8 weeks, and then were trained and tested on either the latent cue preference (LCP) task or the conditioned cue preference (CCP) task in a 3-compartment box apparatus (2 end-compartments and 1 middle-compartment). The end compartments of the box apparatus contained either a single environmental cue (DH-independent) or multiple environmental cues (DH-dependent). During training trials for the LCP and CCP tasks, on alternating days, rats were given access to water in 1 of the 2 end compartments and no water in the opposite end compartment. Rats were water-replete during LCP training and were water-deprived during CCP training. During testing for both tasks, all rats were water-deprived and given free access to all compartments while the amounts of time spent in each compartment were recorded. Results showed that rats given the HFD demonstrated no compartment preferences during both LCP and CCP testing when the compartments contained multiple cues, while rats fed the control diet demonstrated normal compartment preference behavior. However, when the compartments contained a single environmental cue, rats given either the HFD and control diet demonstrated normal LCP and CCP learning. These results demonstrate that consumption of a HFD disrupted both LCP and CCP learning in a multiple-cue (DH-dependent) environment, but did not impair either type of learning in a single-cue (DH-independent) environment. This may be due to selective impairment of the DH caused by increased oxidative stress, inflammation, and/or disrupted neurotransmission produced by consumption of the HFD.

  4. High Fat Diet Inhibits Dendritic Cell and T Cell Response to Allergens but Does Not Impair Inhalational Respiratory Tolerance

    PubMed Central

    Pizzolla, Angela; Oh, Ding Yuan; Luong, Suzanne; Prickett, Sara R.; Henstridge, Darren C.; Febbraio, Mark A.; O’Hehir, Robyn E.; Rolland, Jennifer M.; Hardy, Charles L.

    2016-01-01

    The incidence of obesity has risen to epidemic proportions in recent decades, most commonly attributed to an increasingly sedentary lifestyle, and a ‘western’ diet high in fat and low in fibre. Although non-allergic asthma is a well-established co-morbidity of obesity, the influence of obesity on allergic asthma is still under debate. Allergic asthma is thought to result from impaired tolerance to airborne antigens, so-called respiratory tolerance. We sought to investigate whether a diet high in fats affects the development of respiratory tolerance. Mice fed a high fat diet (HFD) for 8 weeks showed weight gain, metabolic disease, and alteration in gut microbiota, metabolites and glucose metabolism compared to age-matched mice fed normal chow diet (ND). Respiratory tolerance was induced by repeated intranasal (i.n.) administration of ovalbumin (OVA), prior to induction of allergic airway inflammation (AAI) by sensitization with OVA in alum i.p. and subsequent i.n. OVA challenge. Surprisingly, respiratory tolerance was induced equally well in HFD and ND mice, as evidenced by decreased lung eosinophilia and serum OVA-specific IgE production. However, in a pilot study, HFD mice showed a tendency for impaired activation of airway dendritic cells and regulatory T cells compared with ND mice after induction of respiratory tolerance. Moreover, the capacity of lymph node cells to produce IL-5 and IL-13 after AAI was drastically diminished in HFD mice compared to ND mice. These results indicate that HFD does not affect the inflammatory or B cell response to an allergen, but inhibits priming of Th2 cells and possibly dendritic cell and regulatory T cell activation. PMID:27483441

  5. Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies.

    PubMed

    Koziolek, M; Schneider, F; Grimm, M; Modeβ, Chr; Seekamp, A; Roustom, T; Siegmund, W; Weitschies, W

    2015-12-28

    The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosage forms and thus, often associated with the occurrence of food effects on oral bioavailability. In this study, intragastric pH and pressure profiles present after the ingestion of the high-caloric, high-fat (964 kcal) FDA standard breakfast were investigated in 19 healthy human subjects by using the telemetric SmartPill® capsule system (26 × 13 mm). Since the gastric emptying of such large non-digestible objects is typically accomplished by the migrating motor complex phase III activity, the time required for recurrence of fasted state motility determined the gastric emptying time (GET). Following the diet recommendations of the FDA guidance on food effect studies, the mean GET of the telemetric motility capsule was 15.3 ± 4.7 h. Thus, the high caloric value of the standard breakfast impeded gastric emptying before lunch in 18 out of 19 subjects. During its gastric transit, the capsule was exposed to highly dynamic conditions in terms of pH and pressure, which were mainly dependent on further meal and liquid intake, as well as the intragastric capsule deposition behavior. Maximum pH values in the stomach were measured immediately after capsule intake. The median pH value of the 5 min period after capsule ingestion ranged between pH 3.3 and 5.3. Subsequently, the pH decreased relatively constantly and reached minimum values of pH 0-1 after approximately 4 h. The maximum pressure within the stomach amounted to 293 ± 109 mbar and was clearly higher than the maximum pressure measured at the ileocaecal junction (60 ± 35 mbar). The physiological data on the intraluminal conditions within the fed stomach generated in this study will hopefully contribute to a better understanding of food effects on oral drug product performance.

  6. Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta.

    PubMed

    Li, Xinli; Chen, Younan; Liu, Jingping; Yang, Guang; Zhao, Jiuming; Liao, Guangneng; Shi, Meimei; Yuan, Yujia; He, Sirong; Lu, Yanrong; Cheng, Jingqiu

    2012-11-01

    Dyslipidemia caused by 'Western-diet pattern' is a strong risk factor for the onset of diabetes. This study aimed to disclose the relationship between the serum metabolite changes induced by habitual intake of high-fat and high-cholesterol (HFHC) diet and the development of impaired glucose tolerance (IGT) and insulin resistance through animal models of Macaca mulatta. Sixteen M. mulatta (six months old) were fed a control diet or a HFHC diet for 18 months. The diet effect on serum metabolic profiles was investigated by longitudinal research. Islet function was assessed by intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp test. Metabonomics were determined by (1)H proton nuclear magnetic resonance spectroscopy. Prolonged diet-dependent hyperlipidemia facilitated visceral fat accumulation in liver and skeletal muscle and disorder of glucose homeostasis in juvenile monkeys. Glucose disappearance rate (K(Glu)) and insulin response to the glucose challenge effects in HFHC monkeys were significantly lower than in control monkeys. Otherwise, serum trimethylamine-N-oxide (TMAO), lactate and leucine/isoleucine were significantly higher in HFHC monkeys. Sphingomyelin and choline were the most positively correlated with K(Glu) (R(2) = 0.778), as well as negative correlation (R(2) = 0.64) with total cholesterol. The HFHC diet induced visceral fat, abnormal lipid metabolism and IGT prior to weight gain and body fat content increase in juvenile monkeys. We suggest that increased serum metabolites, such as TMAO, lactate, branched-chain amino acids and decreased sphingomyelin and choline, may serve as possible predictors for the evaluation of IGT and insulin resistance risks in the prediabetic state.

  7. Effect of a high-fat meal on thalidomide pharmacokinetics and the relative bioavailability of oral formulations in healthy men and women.

    PubMed

    Teo, S K; Scheffler, M R; Kook, K A; Tracewell, W G; Colburn, W A; Stirling, D I; Thomas, S D

    2000-01-01

    The effect of food on the oral pharmacokinetics of thalidomide and the relative bioavailability of two oral thalidomide formulations were determined in an open label, single dose, randomized, three-way crossover study. Five male and eight female healthy volunteers received a single oral dose of 200 mg Celgene thalidomide capsules under fasted and non-fasted conditions, and a single dose of 200 mg tablets of Serral thalidomide under fasted conditions. The high-fat meal resulted in a 0.5-1.5 h absorption lag time, an increased mean C(max), a decreased mean AUC and a delay in mean T(max). The Serral tablet formulation resulted in a lower mean C(max), and slower terminal decline in plasma thalidomide concentrations compared with both Celgene treatments. Mean C(max) concentrations were 1.99+/-0.41 microg/mL (range 1.28-2.76) within 4.00+/-1.13 h (2-5) for the Celgene formulation fasted, 2.17+/-0.51 microg/mL (1.43-3.01) within 6.08+/-2.33 h (3-12) for the Celgene formulation with food, and 1. 05+/-0.31 microg/mL (0.62-1.65) within 6.23+/-1.88 h (5-10) for the Serral formulation fasted. Mean terminal half-lives were 13.50+/-6. 77 h for the Serral product, compared with 5.80+/-1.72 h and 5. 09+/-1.03 h for Celgene fasted and fed, respectively. Celgene's formulation exhibited slightly greater bioavailability than Serral's formulation, with mean ratios of 122% and 110% for Ln-transformed AUC(0-t) and AUC(0-infinity), respectively. The mean C(max) for the Celgene formulation was approximately two times greater than Serral's. Food delayed the onset of absorption of by 0.5-1.5 h, but had little effect on the extent of absorption from the Celgene capsule. Under fasted conditions, the Celgene thalidomide resulted in a two-fold greater C(max) and 10% greater AUC(0-infinity) than the Serral formulation.

  8. Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding

    PubMed Central

    McMillan, Ryan P.; Wu, Yaru; Voelker, Kevin; Fundaro, Gabrielle; Kavanaugh, John; Stevens, Joseph R.; Shabrokh, Elika; Ali, Mostafa; Harvey, Mordecai; Anderson, Angela S.; Boutagy, Nabil E.; Mynatt, Randall L.; Frisard, Madlyn I.

    2015-01-01

    Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and data from our laboratory have shown that activation of TLR-4 in skeletal muscle via LPS results in decreased fatty acid oxidation (FAO). The purpose of this study was to determine whether overexpression of TLR-4 in skeletal muscle alters mitochondrial function and whole body metabolism in the context of a chow and high-fat diet. C57BL/6J mice (males, 6–8 mo of age) with skeletal muscle-specific overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted in a significant reduction in FAO in muscle homogenates; however, mitochondrial respiration and reactive oxygen species (ROS) production did not appear to be affected on a standard chow diet. To determine the role of TLR-4 overexpression in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly decreased FAO in mTLR-4 mice, which was observed in concert with elevated body weight and fat, greater glucose intolerance, and increase in production of ROS and cellular oxidative damage compared with WT littermates. These findings suggest that TLR-4 plays an important role in the metabolic response in skeletal muscle to high-fat feeding. PMID:26084695

  9. Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding.

    PubMed

    McMillan, Ryan P; Wu, Yaru; Voelker, Kevin; Fundaro, Gabrielle; Kavanaugh, John; Stevens, Joseph R; Shabrokh, Elika; Ali, Mostafa; Harvey, Mordecai; Anderson, Angela S; Boutagy, Nabil E; Mynatt, Randall L; Frisard, Madlyn I; Hulver, Matthew W

    2015-08-01

    Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and data from our laboratory have shown that activation of TLR-4 in skeletal muscle via LPS results in decreased fatty acid oxidation (FAO). The purpose of this study was to determine whether overexpression of TLR-4 in skeletal muscle alters mitochondrial function and whole body metabolism in the context of a chow and high-fat diet. C57BL/6J mice (males, 6-8 mo of age) with skeletal muscle-specific overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted in a significant reduction in FAO in muscle homogenates; however, mitochondrial respiration and reactive oxygen species (ROS) production did not appear to be affected on a standard chow diet. To determine the role of TLR-4 overexpression in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly decreased FAO in mTLR-4 mice, which was observed in concert with elevated body weight and fat, greater glucose intolerance, and increase in production of ROS and cellular oxidative damage compared with WT littermates. These findings suggest that TLR-4 plays an important role in the metabolic response in skeletal muscle to high-fat feeding.

  10. High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering drugs and diet network (GOLDN): an interventional study

    PubMed Central

    2011-01-01

    Background Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat meal. Participants (n = 1048) from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) Study who ingested a high-fat meal were included in this analysis. Lipids were measured at 0 hr (fasting), 3.5 hr, and 6 hr after a standardized fat meal. Particle size distributions were determined using nuclear magnetic resonance spectroscopy. Analyses were stratified by baseline triglycerides (normal vs. elevated) and gender. The effect of PPL on changes in lipoprotein subclasses was assessed using repeated measures ANOVA. Results Postprandially, LDL-C, HDL-C, VLDL-C, and triglycerides increased regardless of baseline triglyceride status, with the largest increases in VLDL-C and TG; however, those with elevated triglycerides demonstrated larger magnitude of response. Total LDL particle number decreased over the 6-hour time interval, mostly from a decrease in the number of small LDL particles. Similarly, total VLDL particle number decreased due to reductions in medium and small VLDL particles. Large VLDL particles and chylomicrons demonstrated the largest increase in concentration. HDL particles demonstrated minimal overall changes in total particle number. Conclusions We have characterized the changes in LDL and VLDL particle number, and their subclass patterns following a high-fat meal. PMID:22008512

  11. Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

    PubMed

    Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

  12. Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study

    PubMed Central

    Glasser, Stephen P.; Wojczynski, Mary K.; Oberman, A. I.; Kabagambe, Edmond K.; Tsai, Michael Y.; Ordovas, Jose M.; Straka, Robert J.; Arnett, Donna K.

    2013-01-01

    Context The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied. Objective To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants. Methods Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree. Results Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/–0.7 to 4 +/–0.4 and 78 / –4 to 36 / –3 nmol/L both P < .0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 = / – 37 to 1088 = / – 36 nmol/L, P < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters. Conclusion Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge. PMID:24971173

  13. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

    PubMed Central

    2009-01-01

    Background The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Methods Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD) or low fat (5%; LFD) chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. Results NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Conclusions Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics. PMID:20034403

  14. Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity

    SciTech Connect

    Tilton, Susan C.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Mikheev, Vladimir B.; Lee, K. M.; Corley, Richard A.; Pounds, Joel G.; Bigelow, Diana J.

    2013-07-01

    Smoking and obesity are each well-established risk factors for cardiovascular heart disease, which together impose earlier onset and greater severity of disease. To identify early signaling events in the response of the heart to cigarette smoke exposure within the setting of obesity, we exposed normal weight and high fat diet-induced obese (DIO) C57BL/6 mice to repeated inhaled doses of mainstream (MS) or sidestream (SS) cigarette smoke administered over a two week period, monitoring effects on both cardiac and pulmonary transcriptomes. MS smoke (250 μg wet total particulate matter (WTPM)/L, 5 h/day) exposures elicited robust cellular and molecular inflammatory responses in the lung with 1466 differentially expressed pulmonary genes (p < 0.01) in normal weight animals and a much-attenuated response (463 genes) in the hearts of the same animals. In contrast, exposures to SS smoke (85 μg WTPM/L) with a CO concentration equivalent to that of MS smoke (250 CO ppm) induced a weak pulmonary response (328 genes) but an extensive cardiac response (1590 genes). SS smoke and to a lesser extent MS smoke preferentially elicited hypoxia- and stress-responsive genes as well as genes predicting early changes of vascular smooth muscle and endothelium, precursors of cardiovascular disease. The most sensitive smoke-induced cardiac transcriptional changes of normal weight mice were largely absent in DIO mice after smoke exposure, while genes involved in fatty acid utilization were unaffected. At the same time, smoke exposure suppressed multiple proteome maintenance genes induced in the hearts of DIO mice. Together, these results underscore the sensitivity of the heart to SS smoke and reveal adaptive responses in healthy individuals that are absent in the setting of high fat diet and obesity.

  15. Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High-Fat Diet/Streptozotocin-Induced Type 2 Diabetic Rats.

    PubMed

    Naowaboot, Jarinyaporn; Somparn, Nuntiya; Saentaweesuk, Suphaket; Pannangpetch, Patchareewan

    2015-06-08

    Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high-fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non-esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα-protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.

  16. 1H NMR-based metabolic fingerprinting of urine metabolites after consumption of lingonberries (Vaccinium vitis-idaea) with a high-fat meal.

    PubMed

    Lehtonen, Henna-Maria; Lindstedt, Anni; Järvinen, Riikka; Sinkkonen, Jari; Graça, Gonçalo; Viitanen, Matti; Kallio, Heikki; Gil, Ana M

    2013-06-01

    The use of NMR metabolomics in clinical trials is growing; however, reports of postprandial experiments in humans are scarce. The present study investigated whether consumption of lingonberries as a supplement to an oil-rich meal modifies the postprandial fingerprints of human urine. Urine samples were analysed by (1)H NMR, and untargeted multivariate analysis was applied to the data for comprehensive fingerprinting. A clear separation of postprandial lingonberry meal samples was revealed. To evaluate statistical differences, a targeted approach was applied for the informative spectral areas. Significantly (p<0.05) increased levels of polyphenol metabolites, hippuric acid and 4-hydroxyhippuric acid, and decreased creatinine and dimethylamine levels were the major explanations for the grouping of the postprandial samples after the different meals. Thus, inclusion of polyphenol-rich lingonberry powder in a rapeseed oil-rich meal modifies the metabolic profile of urine which may be used to reveal both consumption of berries and health-promoting changes in the common metabolism.

  17. Impaired learning and memory in rats induced by a high-fat diet: involvement with the imbalance of nesfatin-1 abundance and copine 6 expression.

    PubMed

    Chen, Zheng; Xu, Ya-Yun; Wu, Rui; Han, Yin-Xiu; Yu, Yue; Ge, Jin-Fang; Chen, Fei-Hu

    2017-02-17

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and the behavior was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST), and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin, and insulin were measured via enzyme-linked immunosorbent assay (ELISA), and the protein expressions of p-GSK-3β, GSK-3β, p-β-catenin, β-catenin, cyclinD, and copine 6 in the hippocampus and prefrontal cortex (PFC) were detected using western blotting. After 4 consecutive weeks of feeding with a high-fat diet, the rats showed obesity; increased plasma concentrations of ALT, glucose, FFA, TC, TG, HDL-C, and LDL-C; decreased plasma levels of leptin and insulin; and inflammation and mild hepatocyte steatosis in the liver. Although there was no significant difference between groups with regard to performance in the OFT, EPM, or FST, the NAFLD rats showed a decreased sucrose preference index in the SPT and impaired learning and memory in the MWM task. Moreover, the present study provides the first evidence of an increased plasma nesfatin-1 concentration in the NAFLD rats, which was significantly correlated with the plasma lipid concentrations and the behavioral performance. Furthermore, copine 6 and p-β-catenin protein expression decreased and p-GSK-3β increased in the hippocampus and PFC of NAFLD rats. These results suggested that consuming of a high-fat diet for 4

  18. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rationale - Obesity is characterized by a chronic pro-inflammatory state that promotes insulin resistance in liver, adipose tissue, and skeletal muscle as well as impairing insulin action in vascular endothelium that contributes to endothelial dysfunction. Cadiovascular complications of obesity are ...

  19. Short-Term High-Fat Diet (HFD) Induced Anxiety-Like Behaviors and Cognitive Impairment Are Improved with Treatment by Glyburide

    PubMed Central

    Gainey, Stephen J.; Kwakwa, Kristin A.; Bray, Julie K.; Pillote, Melissa M.; Tir, Vincent L.; Towers, Albert E.; Freund, Gregory G.

    2016-01-01

    Obesity-associated comorbidities such as cognitive impairment and anxiety are increasing public health burdens that have gained prevalence in children. To better understand the impact of childhood obesity on brain function, mice were fed with a high-fat diet (HFD) from weaning for 1, 3 or 6 weeks. When compared to low-fat diet (LFD)-fed mice (LFD-mice), HFD-fed mice (HFD-mice) had impaired novel object recognition (NOR) after 1 week. After 3 weeks, HFD-mice had impaired NOR and object location recognition (OLR). Additionally, these mice displayed anxiety-like behavior by measure of both the open-field and elevated zero maze (EZM) testing. At 6 weeks, HFD-mice were comparable to LFD-mice in NOR, open-field and EZM performance but they remained impaired during OLR testing. Glyburide, a second-generation sulfonylurea for the treatment of type 2 diabetes, was chosen as a countermeasure based on previous data exhibiting its potential as an anxiolytic. Interestingly, a single dose of glyburide corrected deficiencies in NOR and mitigated anxiety-like behaviors in mice fed with HFD-diet for 3-weeks. Taken together these results indicate that a HFD negatively impacts a subset of hippocampal-independent behaviors relatively rapidly, but such behaviors normalize with age. In contrast, impairment of hippocampal-sensitive memory takes longer to develop but persists. Since single-dose glyburide restores brain function in 3-week-old HFD-mice, drugs that block ATP-sensitive K+ (KATP) channels may be of clinical relevance in the treatment of obesity-associated childhood cognitive issues and psychopathologies. PMID:27563288

  20. A high-fat high-sugar diet-induced impairment in place-recognition memory is reversible and training-dependent.

    PubMed

    Tran, Dominic M D; Westbrook, R Frederick

    2017-03-01

    A high-fat high-sugar (HFHS) diet is associated with cognitive deficits in people and produces spatial learning and memory deficits in rodents. Notable, such diets rapidly impair place-, but not object-recognition memory in rats within one week of exposure. Three experiments examined whether this impairment was reversed by removal of the diet, or prevented by pre-diet training. Experiment 1 showed that rats switched from HFHS to chow recovered from the place-recognition impairment that they displayed while on HFHS. Experiment 2 showed that control rats ("Untrained") who were exposed to an empty testing arena while on chow, were impaired in place-recognition when switched to HFHS and tested for the first time. However, rats tested ("Trained") on the place and object task while on chow, were protected from the diet-induce deficit and maintained good place-recognition when switched to HFHS. Experiment 3 examined the conditions of this protection effect by training rats in a square arena while on chow, and testing them in a rectangular arena while on HFHS. We have previously demonstrated that chow rats, but not HFHS rats, show geometry-based reorientation on a rectangular arena place-recognition task (Tran & Westbrook, 2015). Experiment 3 assessed whether rats switched to the HFHS diet after training on the place and object tasks in a square area, would show geometry-based reorientation in a rectangular arena. The protective benefit of training was replicated in the square arena, but both Untrained and Trained HFHS failed to show geometry-based reorientation in the rectangular arena. These findings are discussed in relation to the specificity of the training effect, the role of the hippocampus in diet-induced deficits, and their implications for dietary effects on cognition in people.

  1. In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring.

    PubMed

    Borengasser, Sarah J; Faske, Jennifer; Kang, Ping; Blackburn, Michael L; Badger, Thomas M; Shankar, Kartik

    2014-12-01

    The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.

  2. Ameliorative effects of α-lipoic acid on high-fat diet-induced oxidative stress and glucose uptake impairment of T cells.

    PubMed

    Cui, Jue; Huang, Dejian; Zheng, Yi

    2016-10-01

    The incidence of obesity and metabolic disease continues to rise, mainly associated with consumption of a high-fat diet (HFD). Previous studies have indicated that HFD could disturb the immune system, leading to immunodeficiency and inflammation. Several mechanisms have been postulated to account for immunodeficiency associated with HFD, one being oxidative stress. To further investigate the effects of HFD on glucose metabolism and proliferative capability of T cells and the protective effects of α-lipoic acid (LA), male C57BL/6J mice were fed a normal chow (10% fat), an HFD (60% fat), an LA supplement (HFD +0.1%LA), and a N-acetyl-L-cysteine supplement (HFD +0.1% NAC) for 10 weeks. Results showed that 10-week HFD increased intracellular reactive oxygen species (ROS) production, induced oxidative stress state formation, inhibited glucose uptake, decreased ATP concentration, reduced proliferative rate, and dampened IL-2 production of T cells of mice. Administration of LA significantly alleviated these changes induced by HFD. These findings reveal that oxidative stress of T cells caused by HFD may be a key factor leading to glucose metabolism reduction and proliferative capability and function impairment of T cells. LA, as a potent agonist, could promote Nrf2 nuclear translocation and up-regulate expression of Nrf2 target genes (Ho-1 and Prdx1), which can eliminate excess ROS and restore redox balance of cells.

  3. Long-term, but not short-term high-fat diet induces fiber composition changes and impaired contractile force in mouse fast-twitch skeletal muscle.

    PubMed

    Eshima, Hiroaki; Tamura, Yoshifumi; Kakehi, Saori; Kurebayashi, Nagomi; Murayama, Takashi; Nakamura, Kyoko; Kakigi, Ryo; Okada, Takao; Sakurai, Takashi; Kawamori, Ryuzo; Watada, Hirotaka

    2017-04-01

    In this study, we investigated the effects of a short-term and long-term high-fat diet (HFD) on morphological and functional features of fast-twitch skeletal muscle. Male C57BL/6J mice were fed a HFD (60% fat) for 4 weeks (4-week HFD) or 12 weeks (12-week HFD). Subsequently, the fast-twitch extensor digitorum longus muscle was isolated, and the composition of muscle fiber type, expression levels of proteins involved in muscle contraction, and force production on electrical stimulation were analyzed. The 12-week HFD, but not the 4-week HFD, resulted in a decreased muscle tetanic force on 100 Hz stimulation compared with control (5.1 ± 1.4 N/g in the 12-week HFD vs. 7.5 ± 1.7 N/g in the control group; P < 0.05), whereas muscle weight and cross-sectional area were not altered after both HFD protocols. Morphological analysis indicated that the percentage of type IIx myosin heavy chain fibers, mitochondrial oxidative enzyme activity, and intramyocellular lipid levels increased in the 12-week HFD group, but not in the 4-week HFD group, compared with controls (P < 0.05). No changes in the expression levels of calcium handling-related proteins and myofibrillar proteins (myosin heavy chain and actin) were detected in the HFD models, whereas fast-troponin T-protein expression was decreased in the 12-week HFD group, but not in the 4-week HFD group (P < 0.05). These findings indicate that a long-term HFD, but not a short-term HFD, impairs contractile force in fast-twitch muscle fibers. Given that skeletal muscle strength largely depends on muscle fiber type, the impaired muscle contractile force by a HFD might result from morphological changes of fiber type composition.

  4. Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats.

    PubMed

    Kim, Yonwook J; Bi, Sheng

    2016-01-15

    Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes.

  5. Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet- fed rats.

    PubMed

    Asadbegi, Masoumeh; Yaghmaei, Parichehreh; Salehi, Iraj; Komaki, Alireza; Ebrahim-Habibi, Azadeh

    2017-03-02

    Obesity and consumption of a high fat diet (HFD) are known to increase the risk of Alzheimer's disease (AD). In the present study, we have examined the protective and therapeutic effects of thymol (main monoterpene phenol found in thyme essential oil) on a HFD-fed rat model of AD. Fourty adult male Wistar rats were randomly assigned to 5 groups:(n = 8 rats/group): group 1, control, consumed an ordinary diet, group 2 consumed a HFD for 8 weeks, then received phosphate-buffered saline (PBS) via intrahippocampal (IHP) injection, group 3 consumed HFD for 8 weeks, then received beta-amyloid (Aβ)1-42 via IHP injections to induce AD, group 4 consumed HFD for 8 weeks, then received Aβ1-42, and was treated by thymol (30 mg/kg in sunflower oil) daily for 4 weeks, and group 5 consumed HFD for 8 week, then received Aβ1-42 after what sunflower oil was administered by oral gavage daily for 4 weeks. Biochemical tests showed an impaired lipid profile and higher glucose levels upon consumption of HFD, which was ameliorated by thymol treatment. In behavioral results, spatial memory in group 3 was significantly impaired, but groups treated with thymol showed better spatial memory compared to group 3 (p ≤ 0.01). In histological results, formation of Aβ plaque in hippocampus of group 3 increased significantly compared to group 1 and group 2 (p ≤ 0.05), but group 4 showed decreased Aβ plaques compared to group 3 (p ≤ 0.01). In conclusion, thymol decreased the effects of Aβ on memory and could be considered as neuroprotective.

  6. High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat ...

  7. Influence of high carbohydrate versus high fat diet in ozone induced pulmonary injury and systemic metabolic impairment in a Brown Norway (BN) rat model of healthy aging

    EPA Science Inventory

    Rationale: Air pollution has been recently linked to the increased prevalence of metabolic syndrome. It has been postulated that dietary risk factors might exacerbate air pollution-induced metabolic impairment. We have recently reported that ozone exposure induces acute systemic ...

  8. High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.

    PubMed

    de Noronha, Sylvana Rendeiro; Campos, Glenda Viggiano; Abreu, Aline Rezende; de Souza, Aline Arlindo; Chianca, Deoclécio A; de Menezes, Rodrigo C

    2017-01-01

    Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear. The current study further investigates the relation between obesity and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45% w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI), a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition, suggesting a positive relation between obesity and the development of an anxiety-like state. The injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors, probably through changes in the GABAergic neurotransmission within the DMH.

  9. Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation.

    PubMed

    Baker, Kathryn D; Reichelt, Amy C

    2016-12-01

    Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet-induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor ΔFosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/ΔFosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders.

  10. Consumption of high-fat meal containing cheese compared with vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomized controlled cross-over study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary recommendations suggest decreased consumption of SFA to minimize CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomized...

  11. Obese adolescents show impaired meal responses of the appetite-regulating hormones ghrelin and PYY.

    PubMed

    Mittelman, Steven D; Klier, Katie; Braun, Sharon; Azen, Colleen; Geffner, Mitchell E; Buchanan, Thomas A

    2010-05-01

    Ghrelin and peptide YY (PYY) stimulate hunger and satiety, respectively. The physiology of these hormones during normal meal intake remains unclear. This study was designed to compare the responses of these two hormones to meal intake between lean and obese Hispanic adolescents. A total of 10 obese and 7 lean Hispanic youth, aged 11-14 years, consumed two mixed meals, one small and one large, during which plasma measurements of active and total ghrelin and total PYY were obtained. Obese subjects tended to consume more calories during the small meal than lean subjects, although this did not reach statistical significance. Intake of the small meal significantly suppressed active ghrelin and stimulated PYY levels in the lean subjects, and these changes were further accentuated by the large meals. In obese subjects, the suppression of active ghrelin and stimulation of PYY by caloric intake were blunted. Interestingly, a paradoxical stimulation of active ghrelin levels was noted during the small meals in both lean and obese subjects. This stimulation was not seen during the larger meals in lean subjects, but remained present in the obese subjects. Thus, meal-related changes in active ghrelin and PYY are blunted in obese as compared to lean Hispanic subjects. This blunting could contribute to the development or worsening of obesity.

  12. High-fat feeding alters the clock synchronization to light.

    PubMed

    Mendoza, Jorge; Pévet, Paul; Challet, Etienne

    2008-12-15

    High-fat feeding in rodents leads to metabolic abnormalities mimicking the human metabolic syndrome, including obesity and insulin resistance. These metabolic diseases are associated with altered temporal organization of many physiological functions. The master circadian clock located in the suprachiasmatic nuclei controls most physiological functions and metabolic processes. Furthermore, under certain conditions of feeding (hypocaloric diet), metabolic cues are capable of altering the suprachiasmatic clock's responses to light. To determine whether high-fat feeding (hypercaloric diet) can also affect resetting properties of the suprachiasmatic clock, we investigated photic synchronization in mice fed a high-fat or chow (low-fat) diet for 3 months, using wheel-running activity and body temperature rhythms as daily phase markers (i.e. suprachiasmatic clock's hands). Compared with the control diet, mice fed with the high-fat diet exhibited increased body mass index, hyperleptinaemia, higher blood glucose, and increased insulinaemia. Concomitantly, high-fat feeding led to impaired adjustment to local time by photic resetting. At the behavioural and physiological levels, these alterations include slower rate of re-entrainment of behavioural and body temperature rhythms after 'jet-lag' test (6 h advanced light-dark cycle) and reduced phase-advancing responses to light. At a molecular level, light-induced phase shifts have been correlated, within suprachiasmatic cells, with a high induction of c-FOS, the protein product of immediate early gene c-fos, and phosphorylation of the extracellular signal-regulated kinases I/II (P-ERK). In mice fed a high-fat diet, photic induction of both c-FOS and P-ERK in the suprachiasmatic nuclei was markedly reduced. Taken together, the present data demonstrate that high-fat feeding modifies circadian synchronization to light.

  13. Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet.

    PubMed

    Carey, Amanda N; Gomes, Stacey M; Shukitt-Hale, Barbara

    2014-05-07

    Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals. It has been demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against putative high-fat diet-related declines, 9-month-old C57Bl/6 mice were maintained on low-fat (10% fat calories) or high-fat (60% fat calories) diets with and without 4% freeze-dried blueberry powder. Novel object recognition memory was impaired by the high-fat diet; after 4 months on the high-fat diet, mice spent 50% of their time on the novel object in the testing trial, performing no greater than chance performance. Blueberry supplementation prevented recognition memory deficits after 4 months on the diets, as mice on this diet spent 67% of their time on the novel object. After 5 months on the diets, mice consuming the high-fat diet passed through the platform location less often than mice on low-fat diets during probe trials on days 2 and 3 of Morris water maze testing, whereas mice consuming the high-fat blueberry diet passed through the platform location as often as mice on the low-fat diets. This study is a first step in determining if incorporating more nutrient-dense foods into a high-fat diet can allay cognitive dysfunction.

  14. Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans.

    PubMed

    Boutagy, Nabil E; Neilson, Andrew P; Osterberg, Kristin L; Smithson, Andrew T; Englund, Tessa R; Davy, Brenda M; Hulver, Matthew W; Davy, Kevin P

    2015-10-01

    The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as L-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μmol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μmol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μmol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μmol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations.

  15. Food shopping, sensory determinants of food choice and meal preparation by visually impaired people. Obstacles and expectations in daily food experiences.

    PubMed

    Kostyra, Eliza; Żakowska-Biemans, Sylwia; Śniegocka, Katarzyna; Piotrowska, Anna

    2017-06-01

    The number of visually impaired and blind people is rising worldwide due to ageing of the global population, but research regarding the impact of visual impairment on the ability of a person to choose food and to prepare meals is scarce. The aim of this study was threefold: to investigate factors determining the choices of food products in people with various levels of impaired vision; to identify obstacles they face while purchasing food, preparing meals and eating out; and to determine what would help them in the areas of food shopping and meal preparation. The data was collected from 250 blind and visually impaired subjects, recruited with the support of the National Association of the Blind. The study revealed that majority of the visually impaired make food purchases at a supermarket or local grocery and they tend to favour shopping for food via the Internet. Direct sale channels like farmers markets were rarely used by the visually impaired. The most frequently mentioned factors that facilitated their food shopping decisions were the assistance of salespersons, product labelling in Braille, scanners that enable the reading of labels and a permanent place for products on the shop shelves. Meal preparation, particularly peeling, slicing and frying, posed many challenges to the visually impaired. More than half of the respondents ate meals outside the home, mainly with family or friends. The helpfulness of the staff and a menu in Braille were crucial for them to have a positive dining out experience. The results of the study provide valuable insights into the food choices and eating experiences of visually impaired people, and also suggest some practical implications to improve their independence and quality of life.

  16. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet

    PubMed Central

    Carter, Lindsay G; Ngo Tenlep, Sara Y; Woollett, Laura A; Pearson, Kevin J

    2016-01-01

    Objective Physical activity has been suggested as a non-pharmacological intervention that can be used to improve glucose homeostasis in women with gestational diabetes mellitus. The purpose of this study was to determine the effects of voluntary exercise on glucose tolerance and body composition in pregnant high fat diet fed mice. Methods Female mice were put on a standard diet or high fat diet for two weeks. The mice were then split into 4 groups; control standard diet fed, exercise standard diet fed, control high fat diet fed, and exercise high fat diet fed. Exercise mice had voluntary access to a running wheel in their home cage one week prior to mating, during mating, and throughout pregnancy. Glucose tolerance and body composition were measured during pregnancy. Akt levels were quantified in skeletal muscle and adipose tissue isolated from saline or insulin injected pregnant dams as a marker for insulin signaling. Results Consumption of the high fat diet led to significantly increased body weight, fat mass, and impaired glucose tolerance in control mice. However, voluntary running in the high fat diet fed dams significantly reduced weight gain and fat mass and ultimately improved glucose tolerance compared to control high fat diet fed dams. Further, body weight, fat mass, and glucose disposal in exercise high fat diet dams were indistinguishable from control dams fed the standard diet. High fat diet fed exercise dams also had significantly increased insulin stimulated phosphorylated Akt expression in adipose tissue, but not skeletal muscle, compared to control dams on high fat diet. Conclusion The use of voluntary exercise improves glucose homeostasis and body composition in pregnant female mice. Thus, future studies could investigate potential long-term health benefits in offspring born to obese exercising dams. PMID:26966635

  17. High-Fat-Diet-Induced Deficits in Dopamine Terminal Function Are Reversed by Restoring Insulin Signaling.

    PubMed

    Fordahl, Steve C; Jones, Sara R

    2017-02-15

    Systemically released insulin crosses the blood-brain barrier and binds to insulin receptors on several neural cell types, including dopaminergic neurons. Insulin has been shown to decrease dopamine neuron firing in the ventral tegmental area (VTA), but potentiate release and reuptake at dopamine terminals in the nucleus accumbens (NAc). Here we show that prolonged consumption of a high fat diet blocks insulin's effects in the NAc, but insulin's effects are restored by inhibiting protein tyrosine phosphatase 1B, which supports insulin receptor signaling. Mice fed a high fat diet (60% kcals from fat) displayed significantly higher fasting blood glucose 160 mg/dL, compared to 101 mg/dL for control-diet-fed mice, and high-fat-diet-fed mice showed reduced blood glucose clearance after an intraperitoneal glucose tolerance test. Using fast scan cyclic voltammetry to measure electrically evoked dopamine in brain slices containing the NAc core, high-fat-diet-fed mice exhibited slower dopamine reuptake compared to control-diet-fed mice (2.2 ± 0.1 and 2.67 ± 0.15 μM/s, respectively). Moreover, glucose clearance rate was negatively correlated with Vmax. Insulin (10 nM to 1 μM) dose dependently increased reuptake rates in control-diet-fed mice compared with in the high-fat-diet group; however, the small molecule insulin receptor sensitizing agent, TCS 401 (300 nM), restored reuptake in high-fat-diet-fed mice to control-diet levels, and a small molecule inhibitor of the insulin receptor, BMS 536924 (300 nM), attenuated reuptake, similar to high-fat-diet-fed mice. These data show that a high-fat diet impairs dopamine reuptake by attenuating insulin signaling at dopamine terminals.

  18. Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding.

    PubMed

    Lépinay, Amandine L; Larrieu, Thomas; Joffre, Corinne; Acar, Niyazi; Gárate, Iciar; Castanon, Nathalie; Ferreira, Guillaume; Langelier, Bénédicte; Guesnet, Philippe; Brétillon, Lionel; Parnet, Patricia; Layé, Sophie; Darnaudéry, Muriel

    2015-03-01

    Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the effects of perinatal HFD combined with exposure to HFD after weaning. Dams were fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) throughout gestation and lactation. At weaning, offspring were placed either on control (C-C, HF-C) or high-fat (HF-HF) diets. In adulthood, hippocampus-dependent memory was assessed using the water-maze task and potential hippocampal alterations were determined by studying PUFA levels, gene expression, neurogenesis and astrocyte morphology. Perinatal HFD induced long-lasting metabolic alterations and some changes in gene expression in the hippocampus, but had no effect on memory. In contrast, spatial memory was impaired in animals exposed to HFD during the perinatal period and maintained on this diet. HF-HF rats also exhibited low n-3 and high n-6 PUFA levels, decreased neurogenesis and downregulated expression of several plasticity-related genes in the hippocampus. To determine the contribution of the perinatal diet to the memory deficits reported in HF-HF animals, an additional experiment was conducted in which rats were only exposed to HFD starting at weaning (C-HF). Interestingly, memory performance in this group was similar to controls. Overall, our results suggest that perinatal exposure to HFD with an unbalanced n-6/n-3 ratio sensitizes the offspring to the adverse effects of subsequent high-fat intake on hippocampal function.

  19. Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia

    PubMed Central

    Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

    2015-01-01

    INTRODUCTION Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. METHODS Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. RESULTS The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). CONCLUSIONS A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men. PMID:26508874

  20. Effect of blueberries on the immune response of obese mice induced by high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Both high fat diet and obesity have been linked to impaired cell-mediated immune response. Blueberry, rich in antioxidant phytochemicals, has been shown to impact biologic functions in several tissues. However, no information is available on immune cells. We investigated whether blueberry consumptio...

  1. A single Mediterranean meal does not impair postprandial flow-mediated dilatation in healthy men with subclinical metabolic dysregulations.

    PubMed

    Lacroix, Sébastien; Des Rosiers, Christine; Gayda, Mathieu; Nozza, Anna; Thorin, Éric; Tardif, Jean-Claude; Nigam, Anil

    2016-08-01

    Cardiovascular risk factors are known to exacerbate high-saturated fatty acid meal (HSFAM)-induced endothelial dysfunction, but the influence of subclinical metabolic dysregulations and the acute impact of a single mixed Mediterranean-type meal (MMM) remains unknown. Thus, this study has the objective to evaluate the metabolic and vascular effect of such meals in healthy subjects with or without subclinical fasting metabolic dysregulations. Twenty-eight healthy males without overt cardiovascular risk factors randomly ingested 1 of 2 isocaloric meals on separate days. Plasma metabolic markers, fatty acid (FA) profile, and endothelial function (flow-mediated dilatation; FMD) were assessed at baseline and 2 and 4 h after meal ingestion. Unsupervised hierarchical clustering identified 2 subgroups of participants (n = 11 and 17) differing by their baseline metabolic profiles. The MMM did not significantly alter postprandial endothelial function in all subjects, irrespective of baseline metabolic parameters. In contrast, the HSFAM induced postprandial endothelial dysfunction (Δ%FMDabsolute = -5.28 ± 2.54, p < 0.01 vs. MMM) in a subgroup of individuals with significantly greater body mass index, fasting insulinemia, and lipid parameters (n = 11). Finally, the postprandial plasma FA profiles were differentially enriched by the HSFAM and MMM, notably with saturated FAs and omega-3 polyunsaturated FAs, respectively. Collectively, our results highlight the detrimental impact of a single HSFAM on endothelial function in healthy individuals displaying subclinical fasting metabolic dysregulations. Such individuals could benefit from MMM, demonstrated herein to be without any acute detriment to endothelial function.

  2. Feeding behavior and body weight development: lessons from rats subjected to gastric bypass surgery or high-fat diet.

    PubMed

    Furnes, M W; Zhao, C-M; Stenstrom, B; Arum, C-J; Tommeras, K; Kulseng, B; Chen, D

    2009-12-01

    Weight loss treatments include diets, drugs, physical training, and surgery, namely bariatric or obesity surgery. The current standard for bariatric surgery is gastric bypass. There are common beliefs that gastric bypass induces body weight loss because of a reduced food intake and that high-fat diet induces overweight and obesity because of overnutrition. The principal aim of the studies on rats summarized herein was to better understand the physiological mechanisms by which gastric bypass achieves body weight loss and by which high-fat diet induces obesity. The results indicated that gastric bypass efficiently reduced body weight, particularly the fat compartment, which was unlikely to be caused by early satiety, reduced food intake or malabsorption, and that large meal size, but not overnutrition, was mainly responsible for high-fat diet-induced obesity. It was unclear whether gastric ghrelin, obestatin and/or amine in the A-like cells were involved in this context.

  3. Supplementary chromium(III) propionate complex does not protect against insulin resistance in high-fat-fed rats.

    PubMed

    Król, Ewelina; Krejpcio, Zbigniew; Iwanik, Katarzyna

    2014-02-01

    Improper eating habits such as high-fat or high-carbohydrate diets are responsible for metabolic changes resulting in impaired glucose tolerance, hyperinsulinemia, insulin resistance, and ultimately diabetes. Although the essentiality of trivalent chromium for humans has been recently questioned by researchers, pharmacological dosages of this element can improve insulin sensitivity in experimental animals and diabetic subjects. The aim of the study was to assess the preventive potential of the supplementary chromium(III) propionate complex (CrProp) in rats fed a high-fat diet. The experiment was conducted on 32 male Wistar rats divided into four groups and fed the following diets: the control (C, AIN-93G), high-fat diets (HF, 40% energy from fat), and a high-fat diet supplemented with CrProp at dosages of 10 and 50 mg Cr/kg diet (HF + Cr10 and HF + Cr50, respectively). After 8 weeks, high-fat feeding led to an increased body mass, hyperinsulinemia, insulin resistance, a decreased serum urea concentration, accumulation of lipid droplets in hepatocytes, and increased renal Fe and splenic Cu contents. Supplementary CrProp in both dosages did not alleviate these changes but increased renal Cr content and normalized splenic Cu content in high-fat-fed rats. Supplementary CrProp does not prevent the development of insulin resistance in rats fed a high-fat diet.

  4. Effect of ethyl pyruvate on skeletal muscle metabolism in rats fed on a high fat diet.

    PubMed

    Olek, Robert A; Ziolkowski, Wieslaw; Wierzba, Tomasz H; Kaczor, Jan J

    2013-07-01

    Impaired mitochondrial capacity may be implicated in the pathology of chronic metabolic diseases. To elucidate the effect of ethyl pyruvate supplementation on skeletal muscles metabolism we examined changes in activities of mitochondrial and antioxidant enzymes, as well as sulfhydryl groups oxidation (an indirect marker of oxidative stress) during the development of obesity. After 6 weeks feeding of control or high fat diet, Wistar rats were divided into four groups: control diet, control diet and ethyl pyruvate, high fat diet, and high fat diet and ethyl pyruvate. Ethyl pyruvate was administered as 0.3% solution in drinking water, for the following 6 weeks. High fat diet feeding induced the increase of activities 3-hydroxyacylCoA dehydrogenase, citrate synthase, and fumarase. Moreover, higher catalase and superoxide dismutase activities, as well as sulfhydryl groups oxidation, were noted. Ethyl pyruvate supplementation did not affect the mitochondrial enzymes' activities, but induced superoxide dismutase activity and sulfhydryl groups oxidation. All of the changes were observed in soleus muscle, but not in extensor digitorum longus muscle. Additionally, positive correlations between fasting blood insulin concentration and activities of catalase (p = 0.04), and superoxide dismutase (p = 0.01) in soleus muscle were noticed. Prolonged ethyl pyruvate consumption elevated insulin concentration, which may cause modifications in oxidative type skeletal muscles.

  5. Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats.

    PubMed

    Tinkov, Alexey A; Popova, Elizaveta V; Polyakova, Valentina S; Kwan, Olga V; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p<0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity.

  6. Effects of lifestyle intervention and meal replacement on glycaemic and body-weight control in Chinese subjects with impaired glucose regulation: a 1-year randomised controlled trial.

    PubMed

    Xu, Dan-Feng; Sun, Jian-Qin; Chen, Min; Chen, Yan-Qiu; Xie, Hua; Sun, Wei-Jia; Lin, Yi-Fan; Jiang, Jing-Jing; Sun, Wei; Chen, Ai-Fang; Tang, Qian-Ru

    2013-02-14

    The purpose of the present study was to evaluate the impact of a lifestyle intervention programme, combined with a daily low-glycaemic index meal replacement, on body-weight and glycaemic control in subjects with impaired glucose regulation (IGR). Subjects with IGR were randomly assigned to an intervention group (n 46) and a control group (n 42). Both groups received health counselling at baseline. The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study, and follow-up visits performed monthly until the end of the 1-year study. Outcome measurements included changes in plasma glucose, glycated Hb (HbA1c), plasma lipids, body weight, blood pressure and body composition (such as body fat mass and visceral fat area). The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group (-1·8 (SEM 0·35) v. -0·6 (SEM 0·40) 2·5 kg, P<0·05). The 2 h plasma glucose concentration decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group (P<0·05) compared with their baseline, respectively. A 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose (P<0·01). The incidence of normal glucose regulation (NGR) in the two groups was significantly different (P=0·001). In conclusion, the combination of regular contact, lifestyle advice and meal replacement is beneficial in promoting IGR to NGR.

  7. Fat Quality Influences the Obesogenic Effect of High Fat Diets

    PubMed Central

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Cancelliere, Rosa; di Fabio, Giovanni; Zarrelli, Armando; Liverini, Giovanna; Iossa, Susanna

    2015-01-01

    High fat and/or carbohydrate intake are associated with an elevated risk for obesity and chronic diseases such as diabetes and cardiovascular diseases. The harmful effects of a high fat diet could be different, depending on dietary fat quality. In fact, high fat diets rich in unsaturated fatty acids are considered less deleterious for human health than those rich in saturated fat. In our previous studies, we have shown that rats fed a high fat diet developed obesity and exhibited a decrease in oxidative capacity and an increase in oxidative stress in liver mitochondria. To investigate whether polyunsaturated fats could attenuate the above deleterious effects of high fat diets, energy balance and body composition were assessed after two weeks in rats fed isocaloric amounts of a high-fat diet (58.2% by energy) rich either in lard or safflower/linseed oil. Hepatic functionality, plasma parameters, and oxidative status were also measured. The results show that feeding on safflower/linseed oil diet attenuates the obesogenic effect of high fat diets and ameliorates the blood lipid profile. Conversely, hepatic steatosis and mitochondrial oxidative stress appear to be negatively affected by a diet rich in unsaturated fatty acids. PMID:26580650

  8. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge.

    PubMed

    Lai, Chao-Qiang; Wojczynski, Mary K; Parnell, Laurence D; Hidalgo, Bertha A; Irvin, Marguerite Ryan; Aslibekyan, Stella; Province, Michael A; Absher, Devin M; Arnett, Donna K; Ordovás, José M

    2016-12-01

    Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4(+) T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10(-7)), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD.

  9. Soy protein isolate inhibits high fat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic consumption by experimental animals of a typical Western diet high in saturated fats and cholesterol during postnatal life has been demonstrated to impair skeletal development. However, the underlying mechanism by which high fat, energy dense diets affect bone-forming cell phenotypes is poor...

  10. Time-dependent regulation of muscle caveolin activation and insulin signalling in response to high-fat diet.

    PubMed

    Gómez-Ruiz, Ana; de Miguel, Carlos; Campión, Javier; Martínez, J Alfredo; Milagro, Fermín I

    2009-10-06

    We studied the effect of high-fat diet on the expression and activation of the three caveolins in rat skeletal muscle and their association with the insulin signalling cascade. Initial response was characterized by increased signalling through Cav-1 and Cav-3 phosphorylation, suggesting that both participate in an initial acute response to the calorie surplus. Afterwards, Cav-1 signalling was slightly reduced, whereas Cav-3 remained active. Late chronic phase signalling through both proteins was impaired inducing a prediabetic state. Summarizing, caveolins seem to mediate a time-dependent regulation of insulin cascade in response to high-fat diet in muscle.

  11. Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition.

    PubMed

    Platt, K M; Charnigo, R J; Pearson, K J

    2014-06-01

    Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10-11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10-11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.

  12. Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity.

    PubMed

    Lőrincz, Kende; Haluszka, Dóra; Kiss, Norbert; Gyöngyösi, Nóra; Bánvölgyi, András; Szipőcs, Róbert; Wikonkál, Norbert M

    2017-04-01

    Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

  13. The Antiinflammatory Cytokine Interleukin-1 Receptor Antagonist Protects from High-Fat Diet-Induced Hyperglycemia

    PubMed Central

    Sauter, Nadine S.; Schulthess, Fabienne T.; Galasso, Ryan; Castellani, Lawrence W.; Maedler, Kathrin

    2008-01-01

    Subclinical inflammation is a recently discovered phenomenon in type 2 diabetes. Elevated cytokines impair β-cell function and survival. A recent clinical trial shows that blocking IL-1β signaling by IL-1 receptor antagonist (IL-1Ra) improves β-cell secretory function in patients with type 2 diabetes. In the present study, we provide further mechanisms of the protective role of IL-1Ra on the β-cell. IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high-fat/high-sucrose diet (HFD) for 12 wk; it improved glucose tolerance and insulin secretion. High-fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which were reduced by IL-1Ra treatment. In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high-fat feeding. Studies on isolated islets revealed that IL-1Ra specifically acted on the β-cell. IL-1Ra protected islets from HFD treated animals from β-cell apoptosis, induced β-cell proliferation, and improved glucose-stimulated insulin secretion. Insulin mRNA was reduced in islets from mice fed a HFD but normalized in the IL-1Ra group. Our results show that IL-1Ra improves β-cell survival and function, and support the potential role for IL-1Ra in the treatment of diabetes. PMID:18239070

  14. Dietary fat and corticosterone levels are contributing factors to meal anticipation

    PubMed Central

    Gyte, Amy; Denn, Mark; Leighton, Brendan; Piggins, Hugh D.

    2016-01-01

    Daily restricted access to food leads to the development of food anticipatory activity and metabolism, which depends upon an as yet unidentified food-entrainable oscillator(s). A premeal anticipatory peak in circulating hormones, including corticosterone is also elicited by daily restricted feeding. High-fat feeding is associated with elevated levels of corticosterone with disrupted circadian rhythms and a failure to develop robust meal anticipation. It is not clear whether the disrupted corticosterone rhythm, resulting from high-fat feeding contributes to attenuated meal anticipation in high-fat fed rats. Our aim was to better characterize meal anticipation in rats fed a low- or high-fat diet, and to better understand the role of corticosterone in this process. To this end, we utilized behavioral observations, hypothalamic c-Fos expression, and indirect calorimetry to assess meal entrainment. We also used the glucocorticoid receptor antagonist, RU486, to dissect out the role of corticosterone in meal anticipation in rats given daily access to a meal with different fat content. Restricted access to a low-fat diet led to robust meal anticipation, as well as entrainment of hypothalamic c-Fos expression, metabolism, and circulating corticosterone. These measures were significantly attenuated in response to a high-fat diet, and animals on this diet exhibited a postanticipatory rise in corticosterone. Interestingly, antagonism of glucocorticoid activity using RU486 attenuated meal anticipation in low-fat fed rats, but promoted meal anticipation in high-fat-fed rats. These findings suggest an important role for corticosterone in the regulation of meal anticipation in a manner dependent upon dietary fat content. PMID:26818054

  15. Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation.

    PubMed

    Teodoro, João Soeiro; Duarte, Filipe Valente; Gomes, Ana Patrícia; Varela, Ana Teresa; Peixoto, Francisco Manuel; Rolo, Anabela Pinto; Palmeira, Carlos Marques

    2013-11-01

    Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the central role of liver and thus hepatic mitochondria in whole-body metabolism, berberine effects on hepatic mitochondrial function in an obesity model are still unknown. Here, we demonstrate that berberine treatment recovers mitochondrial efficiency when altered by a high-fat feeding. Mitochondria isolated from the liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired mitochondrial membrane potential, oxygen consumption and cellular ATP levels. Interestingly, the recovery of mitochondrial function by berberine was associated with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion, berberine potent protective effects against metabolic syndrome may rely on increasing mitochondrial SirT3 activity, normalizing mitochondrial function and preventing a state of energetic deficit caused by impaired OXPHOS.

  16. Easy Meal

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The woman pictured below is sitting down to a nutritious, easily-prepared meal similar to those consumed by Apollo astronauts. The appetizing dishes shown were created simply by adding water to the contents of a Mountain House* Easy Meal package of freeze dried food. The Easy Meal line is produced by Oregon Freeze Dry Foods, Inc., Albany, Oreaon, a pioneer in freeze drying technology and a company long associated with NASA in developing suitable preparations for use on manned spacecraft. Designed to provide nutritionally balanced, attractive hot meals for senior adults, Easy Meal is an offshoot of a 1975-77 demonstration project managed by Johnson Space Center and called Meal System for the Elderly. The project sought ways to help the estimated 3.5 million elderly Americans who are unable to take advantage of existing meal programs. Such services are provided by federal, state and local agencies, but they are not available to many who live in rural areas, or others who are handicapped, temporarily ill or homebound for other reasons. Oregon Freeze Dry Foods was a participant in that multi-agency cooperative project. With its Easy Meal assortment of convenience foods pictured above left, the company is making commercially available meal packages similar to those distributed in the Meal System for the Elderly program. In the freeze drying process, water is extracted from freshly-cooked foods by dehydration at very low temperatures, as low as 50 I degrees below zero. Flavor is locked in by packaging the dried food in pouches which block out moisture and oxygen, the principal causes of food deterioration; thus the food can be stored for long periods without refrigeration. Meals are reconstituted by adding hot or cold water, depending on the type of food, and they are table ready in five to 10 minutes. Oregon Freeze Dry Foods offers five different meal packages and plans to expand the line.

  17. The acute effects of time-of-day-dependent high fat feeding on whole body metabolic flexibility in mice

    PubMed Central

    Joo, J; Cox, C C; Kindred, E D; Lashinger, L M; Young, M E; Bray, M S

    2016-01-01

    Background: Both circadian disruption and timing of feeding have important roles in the development of metabolic disease. Despite growing acceptance that the timing of food consumption has long-term impact on metabolic homeostasis, little is known regarding the immediate influence on whole body metabolism, or the mechanisms involved. We aimed to examine the acute effects of time-of-day-dependent high fat feeding on whole body substrate metabolism and metabolic plasticity, and to determine the potential contribution of the adipocyte circadian clock. Methods: Mice were fed a regimen of 4-h meal at the beginning and end of the dark (waking) cycle, separated by 4 h of fasting. Daily experimental conditions consisted of either an early very high fat or high fat (EVHF or EHF, 60 or 45% kcals from fat, respectively) or late (LVHF or LHF) meal, paired with a low fat (LF, 10% kcals from fat) meal. Metabolic parameters, glucose tolerance, body fat composition and weight were assessed. To determine the role of the adipocyte circadian clock, an aP2-CLOCK mutant (ACM) mouse model was used. Results: Mice in the EVHF or EHF groups showed a 13.2 or 8.84 higher percentage of caloric intake from fat and had a 0.013 or 0.026 lower daily average respiratory exchange ratio, respectively, compared with mice eating the opposite feeding regime. Changes in glucose tolerance, body fat composition and weight were not significant at the end of the 9-day restricted feeding period. ACM mice did not exhibit different metabolic responses to the feeding regimes compared with wild-type littermates. Circadian clock disruption did not influence the short-term response to timed feeding. Conclusions: Both the total fat composition of diet and the timing of fat intake may differentially mediate the effect of timed feeding on substrate metabolism, but may not induce acute changes in metabolic flexibility. PMID:27133618

  18. The association between LRP-1 variants and chylomicron uptake after a high fat meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro studies suggest that low density lipoprotein receptor-related protein 1 (LRP1) plays a role in the secondary uptake of chylomicrons. In addition, in vivo studies using LRP-1 knockout mice show these animals exhibit delayed chylomicron clearance. Whether this is true in humans is unknown. We...

  19. Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism.

    PubMed

    Sid, Victoria; Wu, Nan; Sarna, Lindsei K; Siow, Yaw L; House, James D; O, Karmin

    2015-11-15

    AMPK is an endogenous energy sensor that regulates lipid and carbohydrate metabolism. Nonalcoholic fatty liver disease (NAFLD) is regarded as a hepatic manifestation of metabolic syndrome with impaired lipid and glucose metabolism and increased oxidative stress. Our recent study showed that folic acid supplementation attenuated hepatic oxidative stress and lipid accumulation in high-fat diet-fed mice. The aim of the present study was to investigate the effect of folic acid on hepatic AMPK during high-fat diet feeding and the mechanisms involved. Male C57BL/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26 mg/kg diet) for 5 wk. Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels. Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the liver.

  20. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    PubMed

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  1. Supplementation of a high-fat diet with chlorogenic acid is associated with insulin resistance and hepatic lipid accumulation in mice.

    PubMed

    Mubarak, Aidilla; Hodgson, Jonathan M; Considine, Michael J; Croft, Kevin D; Matthews, Vance B

    2013-05-08

    The increasing prevalence of the metabolic syndrome requires a greater need for therapeutic and prevention strategies. Higher coffee consumption is consistently associated with a lower risk of type 2 diabetes in population studies. Dietary polyphenols have been linked to benefits on several features of the metabolic syndrome. Chlorogenic acid (CGA), a major component of coffee, is one of the most consumed polyphenols in the diet. In our study, we conducted a controlled dietary intervention over 12 weeks in male mice. There were three dietary groups: (i) normal diet, (ii) high-fat diet, and (iii) high-fat diet + CGA. We assessed the effect of CGA at a physiologically obtainable dose (1 g/kg of diet) on high-fat-diet-induced obesity, glucose intolerance, insulin resistance, and also fatty acid oxidation and insulin signaling in C57BL/6 male mice. Supplementation of CGA in the high-fat diet did not reduce body weight compared to mice fed the high-fat diet alone (p = 0.32). CGA resulted in increased insulin resistance compared to mice fed a high-fat diet only (p < 0.05). CGA resulted in decreased phosphorylation of AMP-activated protein kinase (AMPK) (p < 0.001) and acetyl carboxylase β (ACCβ), a downstream target of AMPK (p < 0.05), in liver. The liver of mice fed a high-fat diet supplemented with CGA had a higher lipid content (p < 0.05) and more steatosis relative to mice fed a high-fat diet only, indicating impaired fatty acid oxidation. This study suggests that CGA supplementation in a high-fat diet does not protect against features of the metabolic syndrome in diet-induced obese mice.

  2. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    PubMed

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.

  3. Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet.

    PubMed

    Gault, V A; Porter, W D; Flatt, P R; Hölscher, C

    2010-08-01

    High-calorie diet has been shown to impair learning ability and hippocampal synaptic plasticity in rodents. This study examined effects of daily treatment with the glucagon-like peptide-1 mimetic, exendin-4, on cognitive function and hippocampal synaptic plasticity in a model of diet-induced obesity, which exhibits compromised cognitive performance. Mice fed a high-fat diet were treated with exendin-4 (25 nmol kg(-1) bodyweight; twice daily) or saline vehicle (0.9% (w/v) NaCl) over 21 days. In addition to improving metabolic control, exendin-4-treated mice exhibited a marked increase in recognition index highlighting improved learning and memory. High-fat diet resulted in the elimination of in vivo electrophysiological long-term potentiation, which was rescued following exendin-4 treatment. This study shows that exendin-4 therapy improves cognitive function and ameliorates impaired hippocampal synaptic plasticity in dietary-induced obesity.

  4. Hepatic NAD salvage pathway is enhanced in mice on a high-fat diet.

    PubMed

    Penke, Melanie; Larsen, Per S; Schuster, Susanne; Dall, Morten; Jensen, Benjamin A H; Gorski, Theresa; Meusel, Andrej; Richter, Sandy; Vienberg, Sara G; Treebak, Jonas T; Kiess, Wieland; Garten, Antje

    2015-09-05

    Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme for NAD salvage and the abundance of Nampt has been shown to be altered in non-alcoholic fatty liver disease. It is, however, unknown how hepatic Nampt is regulated in response to accumulation of lipids in the liver of mice fed a high-fat diet (HFD). HFD mice gained more weight, stored more hepatic lipids and had an impaired glucose tolerance compared with control mice. NAD levels as well as Nampt mRNA expression, protein abundance and activity were significantly increased in HFD mice. Enhanced NAD levels were associated with deacetylation of p53 and Nfκb indicating increased activation of Sirt1. Despite impaired glucose tolerance and increased hepatic lipid levels in HFD mice, NAD metabolism was significantly enhanced. Thus, improved NAD metabolism may be a compensatory mechanism to protect against negative impact of hepatic lipid accumulation.

  5. Shift of circadian feeding pattern by high-fat diets is coincident with reward deficits in obese mice.

    PubMed

    Morales, Lidia; Del Olmo, Nuria; Valladolid-Acebes, Ismael; Fole, Alberto; Cano, Victoria; Merino, Beatriz; Stucchi, Paula; Ruggieri, Daniela; López, Laura; Alguacil, Luis Fernando; Ruiz-Gayo, Mariano

    2012-01-01

    Recent studies provide evidence that high-fat diets (HF) trigger both i) a deficit of reward responses linked to a decrease of mesolimbic dopaminergic activity, and ii) a disorganization of circadian feeding behavior that switch from a structured meal-based schedule to a continuous snacking, even during periods normally devoted to rest. This feeding pattern has been shown to be a cause of HF-induced overweight and obesity. Our hypothesis deals with the eventual link between the rewarding properties of food and the circadian distribution of meals. We have investigated the effect of circadian feeding pattern on reward circuits by means of the conditioned-place preference (CPP) paradigm and we have characterized the rewarding properties of natural (food) and artificial (cocaine) reinforcers both in free-feeding ad libitum HF mice and in HF animals submitted to a re-organized feeding schedule based on the standard feeding behavior displayed by mice feeding normal chow ("forced synchronization"). We demonstrate that i) ad libitum HF diet attenuates cocaine and food reward in the CPP protocol, and ii) forced synchronization of feeding prevents this reward deficit. Our study provides further evidence that the rewarding impact of food with low palatability is diminished in mice exposed to a high-fat diet and strongly suggest that the decreased sensitivity to chow as a positive reinforcer triggers a disorganized feeding pattern which might account for metabolic disorders leading to obesity.

  6. Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice

    PubMed Central

    2016-01-01

    Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice. PMID:27960282

  7. Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

    PubMed Central

    Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

    2015-01-01

    Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities. PMID:25945108

  8. Actions of incretin metabolites on locomotor activity, cognitive function and in vivo hippocampal synaptic plasticity in high fat fed mice.

    PubMed

    Porter, David; Faivre, Emilie; Flatt, Peter R; Hölscher, Christian; Gault, Victor A

    2012-05-01

    The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity-diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9-36)amide and GIP(3-42), respectively. Therefore, the present study investigated effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive function and hippocampal synaptic plasticity in mice with diet-induced obesity and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide, GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any changes in bodyweight, non-fasting plasma glucose and plasma insulin concentrations or glucose tolerance compared with high-fat saline controls. Similarly, locomotor and feeding activity, O(2) consumption, CO(2) production, respiratory exchange ratio and energy expenditure were not altered by chronic treatment with incretin metabolites. Administration of the truncated metabolites did not alter general behavior in an open field test or learning and memory ability as recorded during an object recognition test. High-fat mice exhibited a significant impairment in hippocampal long-term potentiation (LTP) which was not affected by treatment with incretin metabolites. These data indicate that incretin metabolites do not influence locomotor activity, cognitive function and hippocampal synaptic plasticity when administered at pharmacological doses to mice fed a high-fat diet.

  9. Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice.

    PubMed

    Sun, Quancai; Xiao, Xiao; Kim, Yoo; Kim, Daeyoung; Yoon, Kyoon Sup; Clark, John M; Park, Yeonhwa

    2016-12-14

    Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice.

  10. Attentional bias in restrictive eating disorders. Stronger attentional avoidance of high-fat food compared to healthy controls?

    PubMed

    Veenstra, Esther M; de Jong, Peter J

    2012-02-01

    A striking feature of the restricting subtype of anorexia nervosa (AN) is that these patients are extremely successful in restricting their food intake. Possibly, they are highly efficient in avoiding attentional engagement of food cues, thereby preventing more elaborate processing of food cues and thus subsequent craving. This study examined whether patients diagnosed with restrictive eating disorders ('restricting AN-like patients'; N=88) indeed show stronger attentional avoidance of visual food stimuli than healthy controls (N=76). Attentional engagement and disengagement were assessed by means of a pictorial exogenous cueing task, and (food and neutral) pictures were presented for 300, 500, or 1000 ms. In the 500 ms condition, both restricting AN-like patients and healthy controls demonstrated attentional avoidance of high-fat food as indexed by a negative cue-validity effect and impaired attentional engagement with high-fat food, whereas no evidence was found for facilitated disengagement from high-fat food. Within the group of restricting AN-like patients, patients with relatively severe eating pathology showed relatively strong attentional engagement with low-fat food. There was no evidence for attentional bias in the 300 and 1000 ms condition. The pattern of findings indicate that attentional avoidance of high-fat food is a common phenomenon that may become counterproductive in restricting AN-like patients, as it could facilitate their restricted food intake.

  11. High-fat and ketogenic diets in amyotrophic lateral sclerosis.

    PubMed

    Paganoni, Sabrina; Wills, Anne-Marie

    2013-08-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

  12. Beneficial effects of hydro-alcoholic extract of Caralluma fimbriata against high-fat diet-induced insulin resistance and oxidative stress in Wistar male rats.

    PubMed

    Sudhakara, G; Mallaiah, P; Sreenivasulu, N; Sasi Bhusana Rao, B; Rajendran, R; Saralakumari, D

    2014-06-01

    The main aim of this study was to investigate the beneficial effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) on the effects of high-fat diet feeding on insulin resistance and oxidative stress in Wistar rats. High-fat diet (60% of fat) and CFE (200 mg/kg body weight/day) were given concurrently to the rats for a period of 90 days. Feeding with high-fat diet resulted in the development of hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia and impaired insulin sensitivity (P < 0.05). Administration of CFE to high-fat diet-fed rats for 90 days resulted in a significant improvement in plasma glucose, insulin, leptin, and triglycerides. Regarding liver antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation and lower GSH levels and lower activities of enzymatic antioxidants, while CFE treatment prevented all these observed abnormalities. In conclusion, intake of CFE may be beneficial for the suppression of high-fat diet-induced insulin resistance and oxidative stress.

  13. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    PubMed

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

  14. Nox2 mediates skeletal muscle insulin resistance induced by a high fat diet.

    PubMed

    Souto Padron de Figueiredo, Alvaro; Salmon, Adam B; Bruno, Francesca; Jimenez, Fabio; Martinez, Herman G; Halade, Ganesh V; Ahuja, Seema S; Clark, Robert A; DeFronzo, Ralph A; Abboud, Hanna E; El Jamali, Amina

    2015-05-22

    Inflammation and oxidative stress through the production of reactive oxygen species (ROS) are consistently associated with metabolic syndrome/type 2 diabetes. Although the role of Nox2, a major ROS-generating enzyme, is well described in host defense and inflammation, little is known about its potential role in insulin resistance in skeletal muscle. Insulin resistance induced by a high fat diet was mitigated in Nox2-null mice compared with wild-type mice after 3 or 9 months on the diet. High fat feeding increased Nox2 expression, superoxide production, and impaired insulin signaling in skeletal muscle tissue of wild-type mice but not in Nox2-null mice. Exposure of C2C12 cultured myotubes to either high glucose concentration, palmitate, or H2O2 decreases insulin-induced Akt phosphorylation and glucose uptake. Pretreatment with catalase abrogated these effects, indicating a key role for H2O2 in mediating insulin resistance. Down-regulation of Nox2 in C2C12 cells by shRNA prevented insulin resistance induced by high glucose or palmitate but not H2O2. These data indicate that increased production of ROS in insulin resistance induced by high glucose in skeletal muscle cells is a consequence of Nox2 activation. This is the first report to show that Nox2 is a key mediator of insulin resistance in skeletal muscle.

  15. High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.

    PubMed

    Arnold, Steven E; Lucki, Irwin; Brookshire, Bethany R; Carlson, Gregory C; Browne, Caroline A; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F; Kim, Sangwon F

    2014-07-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.

  16. Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

    PubMed Central

    Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

    2016-01-01

    A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

  17. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  18. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge[S

    PubMed Central

    Lai, Chao-Qiang; Wojczynski, Mary K.; Parnell, Laurence D.; Hidalgo, Bertha A.; Irvin, Marguerite Ryan; Aslibekyan, Stella; Province, Michael A.; Absher, Devin M.; Arnett, Donna K.; Ordovás, José M.

    2016-01-01

    Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 × 10−7), but no methylation site reached epigenome-wide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genome-wide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD. PMID:27777315

  19. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin resistance leads to memory impairment. Cinnamon (CN) improves whole body insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling, and Alzheimer-associated gene expression in the brain were measured in male Wistar rats fed a high fat/high fructose...

  20. Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity.

    PubMed

    Wu, Ueyue; Cha, Ying; Huang, Xinmei; Liu, Jun; Chen, Zaoping; Wang, Fang; Xu, Jiong; Sheng, Li; Ding, Heyuan

    2015-01-01

    Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-α. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage.

  1. Meal Plans.

    ERIC Educational Resources Information Center

    Pence, John T.

    Changing life styles for college students are causing food service directors to change their ways of serving students. Students today seem to prefer living in privately owned apartments and houses where they can provide and cook their own food to living on campus and having meals prepared for them. Many colleges and universities are eliminating…

  2. Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction.

    PubMed

    Fu, Zhuo; Wu, Jing; Nesil, Tanseli; Li, Ming D; Aylor, Kevin W; Liu, Zhenqi

    2017-02-01

    Insulin action on hippocampus improves cognitive function, and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen, and hormones such as insulin to cerebral parenchyma, including hippocampus. In skeletal muscle, insulin actively regulates microvascular opening and closure, and this action is impaired in the insulin-resistant states. To examine insulin's action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity, we determined cognitive function and microvascular insulin responses, parenchyma insulin responses, and capillary density in the hippocampus in 2- and 8-mo-old rats on chow diet and 8-mo-old rats on a long-term high-fat diet (6 mo). Insulin infusion increased hippocampal microvascular perfusion in rats on chow diet by ~80-90%. High-fat diet feeding completely abolished insulin-mediated microvascular responses and protein kinase B phosphorylation but did not alter the capillary density in the hippocampus. This was associated with a significantly decreased cognitive function assessed using both the two-trial spontaneous alternation behavior test and the novel object recognition test. As the microvasculature provides the needed endothelial surface area for delivery of nutrients, oxygen, and insulin to hippocampal parenchyma, we conclude that hippocampal microvascular insulin resistance may play a critical role in the development of cognitive impairment seen in obesity and diabetes. Our results suggest that improvement in hippocampal microvascular insulin sensitivity might help improve or reverse cognitive function in the insulin-resistant states.

  3. Persistent Chromatin Modifications Induced by High Fat Diet.

    PubMed

    Leung, Amy; Trac, Candi; Du, Juan; Natarajan, Rama; Schones, Dustin E

    2016-05-13

    Obesity is a highly heritable complex disease that results from the interaction of multiple genetic and environmental factors. Formerly obese individuals are susceptible to metabolic disorders later in life, even after lifestyle changes are made to mitigate the obese state. This is reminiscent of the metabolic memory phenomenon originally observed for persistent complications in diabetic patients, despite subsequent glycemic control. Epigenetic modifications represent a potential mediator of this observed memory. We previously demonstrated that a high fat diet leads to changes in chromatin accessibility in the mouse liver. The regions of greatest chromatin changes in accessibility are largely strain-dependent, indicating a genetic component in diet-induced chromatin alterations. We have now examined the persistence of diet-induced chromatin accessibility changes upon diet reversal in two strains of mice. We find that a substantial fraction of loci that undergo chromatin accessibility changes with a high fat diet remains in the remodeled state after diet reversal in C57BL/6J mice. In contrast, the vast majority of diet-induced chromatin accessibility changes in A/J mice are transient. Our data also indicate that the persistent chromatin accessibility changes observed in C57BL/6J mice are associated with specific transcription factors and histone post-translational modifications. The persistent loci identified here are likely to be contributing to the overall phenotype and are attractive targets for therapeutic intervention.

  4. High-fat diet alters gut microbiota physiology in mice.

    PubMed

    Daniel, Hannelore; Gholami, Amin Moghaddas; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-02-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level.

  5. Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin

    2014-08-25

    Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.

  6. Consequences of a Maternal High-Fat Diet and Late Gestation Diabetes on the Developing Rat Lung

    PubMed Central

    Forred, Benjamin J.; Larsen, Tricia D.; Jensen, Danielle N.; Wachal, Angela L.; Khan, Muhammad Ali; Vitiello, Peter F.

    2016-01-01

    expression, and an impaired Txnip/VEGF pathway that are important for vessel growth and migration. After 3 weeks, mortality remained highest and static lung compliance and hysteresis were lowest in combination-exposed offspring. Conclusion This study emphasizes the effects of a maternal high-fat diet, especially alongside late-gestation diabetes, on pulmonary vasculogenesis, demonstrates adverse consequences beyond the perinatal period and directs attention to mechanistic pathways of interest. Findings provide a foundation for additional investigation of preventative and therapeutic strategies aimed at decreasing pulmonary morbidity in at-risk infants. PMID:27518105

  7. Effects of glucose-dependent insulinotropic polypeptide receptor knockout and a high-fat diet on cognitive function and hippocampal gene expression in mice.

    PubMed

    Lennox, Rachel; Lennox, Rachael R; Moffett, R Charlotte; Moffett, Charlotte; Porter, David W; Irwin, Nigel; Gault, Victor A; Flatt, Peter R

    2015-07-01

    It has been previously demonstrated that compromise of glucose-dependent insulinotropic polypeptide receptor (GIPR) action and chronic consumption of a high-fat diet can independently impair memory and learning ability, however, the underlying pathology remain to be elucidated. The present study investigated the effects of GIPR knockout (KO), alone and in combination with a high-fat diet, on aspects of cognitive function and hippocampal gene expression in mice. In object recognition tests, normal mice exhibited effective memory, preferring to investigate the novel over the familiar object. However, wild-type (WT) mice fed a high-fat diet and GIPR KO mice fed a standard or high-fat diet demonstrated no such discrimination, suggesting the impairment of memory function. This decline in cognitive function was associated with marked changes in the expression levels of hippocampal genes involved in memory and learning. The chronic consumption of a high-fat diet decreased the hippocampal gene expression levels of mammalian target of rapamycin (mTOR), neurotrophic tyrosine kinase receptor type 2 (NTRK2) and synaptophysin. Notably, the GIPR KO mice fed a high-fat diet exhibited no reduction in the hippocampal expression of synaptophysin expression, however, the GIPR KO mice fed a standard rodent maintenance diet exhibited reduced hippocampal expression of mTOR compared with the WT controls. These data highlighted the importance of intact GIPR signalling and dietary composition in modulating memory and learning, and hippocampal pathways involved in the maintenance of synaptic plasticity, including mTOR and NTRK2, appear to be key in this regard.

  8. Leucine supplementation at the onset of high-fat feeding does not prevent weight gain or improve glycemic regulation in male Sprague-Dawley rats.

    PubMed

    Baum, Jamie I; Washington, Tyrone A; Shouse, Stephanie A; Bottje, Walter; Dridi, Sami; Davis, Gina; Smith, Dameon

    2016-12-01

    Obesity is a major public health concern and it is essential to identify effective treatments and preventative strategies to stop continued increases in obesity rates. The potential functional roles of the branched chain amino acid leucine make this amino acid an attractive candidate for the treatment and/or prevention of obesity. The objective of this study was to determine if long-term leucine supplementation could prevent the development of obesity and reduce the risk factors for chronic disease in rats fed a high-fat (60 % fat) diet. Male Sprague-Dawley rats (n = 30 per dietary treatment) were meal-fed (3 meals/day) either a control, low-fat diet (LF), control + leucine (LFL), high-fat (HF), or high-fat + leucine (HFL) for 42 days. On day 42, rats were sacrificed at 0, 30, or 90 min postprandial. Animals fed the HF and HFL diets had higher (P < 0.05) final body weights and weight gain compared to animals fed the LF and LFL diets. Leucine supplementation increased epididymal fat mass (P < 0.05) and decreased muscle mass (P < 0.05). There was no effect of leucine supplementation on postprandial glucose or insulin response. However, there was a significant effect (P < 0.05) of diet and time on free fatty acid concentrations. There was no effect of leucine on muscle markers of protein synthesis (4E-BP1, p70S6K) or energy metabolism (Akt, AMPK). Leucine supplementation decreased (P < 0.05) PGC1α expression and increased (P < 0.05) PPARγ expression in skeletal muscle. In conclusion, long-term leucine supplementation does not prevent weight gain, improve body composition, or improve glycemic control in rats fed a high-fat diet.

  9. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  10. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  11. Sphingolipids in High Fat Diet and Obesity-Related Diseases

    PubMed Central

    Choi, Songhwa; Snider, Ashley J.

    2015-01-01

    Nutrient oversupply associated with a high fat diet (HFD) significantly alters cellular metabolism, and specifically including sphingolipid metabolism. Sphingolipids are emerging as bioactive lipids that play key roles in regulating functions, in addition to their traditional roles as membrane structure. HFD enhances de novo sphingolipid synthesis and turnover of sphingolipids via the salvage pathway, resulting in the generation of ceramide, and more specifically long chain ceramide species. Additionally, HFD elevates sphingomyelin and sphingosine-1 phosphate (S1P) levels in several tissues including liver, skeletal muscle, adipose tissue, and cardiovascular tissues. HFD-stimulated sphingolipid generation contributes to systemic insulin resistance, dysregulated lipid accumulation, and cytokine expression and secretion from skeletal muscle and adipose tissues, exacerbating obesity-related conditions. Furthermore, altered sphingolipid levels, particularly ceramide and sphingomyelin, are involved in obesity-induced endothelial dysfunction and atherosclerosis. In this review, HFD-mediated sphingolipid metabolism and its impact on HFD-induced biology and pathobiology will be discussed. PMID:26648664

  12. Novel insulin delivery profiles for mixed meals for sensor-augmented pump and closed-loop artificial pancreas therapy for type 1 diabetes mellitus.

    PubMed

    Srinivasan, Asavari; Lee, Joon Bok; Dassau, Eyal; Doyle, Francis J

    2014-09-01

    Maintaining euglycemia for people with type 1 diabetes is highly challenging, and variations in glucose absorption rates with meal composition require meal type specific insulin delivery profiles for optimal blood glucose control. Traditional basal/bolus therapy is not fully optimized for meals of varied fat contents. Thus, regimens for low- and high-fat meals were developed to improve current insulin pump therapy. Simulations of meals with varied fat content demonstrably replicated published data. Subsequently, an insulin profile library with optimized delivery regimens under open and closed loop for various meal compositions was constructed using particle swarm optimization. Calculations showed that the optimal basal bolus insulin profiles for low-fat meals comprise a normal bolus or a short wave. The preferred delivery for high-fat meals is typically biphasic, but can extend to multiple phases depending on meal characteristics. Results also revealed that patients that are highly sensitive to insulin could benefit from biphasic deliveries. Preliminary investigations of the optimal closed-loop regimens also display bi- or multiphasic patterns for high-fat meals. The novel insulin delivery profiles present new waveforms that provide better control of postprandial glucose excursions than existing schemes. Furthermore, the proposed novel regimens are also more or similarly robust to uncertainties in meal parameter estimates, with the closed-loop schemes demonstrating superior performance and robustness.

  13. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance

    PubMed Central

    McNay, Ewan C.; Ong, Cecilia T.; McCrimmon, Rory J.; Cresswell, James; Bogan, Jonathan S.; Sherwin, Robert S

    2010-01-01

    Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes. PMID:20176121

  14. Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance

    PubMed Central

    Zhu, Caihong; Schwarz, Petra; Abakumova, Irina; Aguzzi, Adriano

    2015-01-01

    Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer’s disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer’s disease. In addition, impaired insulin signaling in the Alzheimer’s disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis. PMID:26658276

  15. Impaired gastric emptying of a solid test meal in patients with Parkinson's disease using 13C-sodium octanoate breath test.

    PubMed

    Goetze, Oliver; Wieczorek, Joerg; Mueller, Thomas; Przuntek, Horst; Schmidt, Wolfgang E; Woitalla, Dirk

    2005-03-03

    Up to now gastric emptying in patients with Parkinson's disease was determined by radioscintigraphy. The 13C-sodium octanoate breath test (OBT) has been established for the non-invasive evaluation of gastric emptying with a solid test meal. The aim of the study was to evaluate the OBT in patients with Parkinson's disease and to investigate the prevalence of delayed gastric emptying for solids in PD and the relationship to clinical staging patterns. Twenty-two healthy subjects and 36 patients with different clinical stages of PD classified using Hoehn and Yahr (H&Y) and Unified Parkinson's Disease Rating Scale (UPDRS) were studied. Each fasting control and patient received a solid test meal (241 kcal) labelled with 100 mg of 13C-sodium octanoate. Breath samples were obtained before substrate administration and then in 15-min intervals over 4 h. The 13CO2/12CO2 ratio was determined in each breath sample as delta over baseline. Time to peak (t(peak)), gastric half emptying time (t1/2b), lag phase (t(lagb)) and gastric emptying coefficient (GEC) were calculated. Significant differences in t(peak), t1/2b, t(lagb) and GEC were found between patients and healthy volunteers (p<0.0001), with a 60% delay in gastric half emptying time in the patient group. Gastric half emptying time was different between clinical disease groups (H&Y 0-2 versus H&Y 2.5-5, p=0.001; UPDRS 0-30 versus UPDRS 61-92, p<0.05). The OBT detects a significant delay in gastric emptying of a solid test meal in patients with PD. Delayed gastric emptying for solids is associated with disease severity.

  16. Time-restricted feeding reduces adiposity in mice fed a high-fat diet.

    PubMed

    Sundaram, Sneha; Yan, Lin

    2016-06-01

    Disruption of the circadian rhythm contributes to obesity. This study tested the hypothesis that time-restricted feeding (TRF) reduces high-fat diet-induced increase in adiposity. Male C57BL/6 mice were fed the AIN93G or the high-fat diet ad libitum (ad lib); TRF of the high-fat diet for 12 or 8hours during the dark cycle was initiated when high-fat diet-fed mice exhibited significant increases in body weight. Energy intake of the TRF 12-hour group was not different from that of the high-fat ad lib group, although that of the TRF 8-hour group was slightly but significantly lower. Restricted feeding of the high-fat diet reduced body fat mass and body weight compared with mice fed the high-fat diet ad lib. There were no differences in respiratory exchange ratio (RER) among TRF and high-fat ad lib groups, but the RER of these groups was lower than that of the AIN93G group. Energy expenditure of the TRF groups was slightly but significantly lower than that of the high-fat ad lib group. Plasma concentrations of ghrelin were increased in TRF groups compared with both AIN93G and high-fat ad lib groups. Elevations of plasma concentrations of insulin, leptin, monocyte chemoattractant protein-1, and tissue inhibitor metalloproteinase-1 by high-fat ad lib feeding were reduced by TRF to the levels of mice fed the AIN93G diet. In conclusion, TRF during the dark cycle reduces high-fat diet-induced increases in adiposity and proinflammatory cytokines. These results indicate that circadian timing of food intake may prevent obesity and abate obesity-related metabolic disturbance.

  17. Effects of Glycyrrhiza glabra polysaccharides on immune and antioxidant activities in high-fat mice.

    PubMed

    Hong, Ying-Kai; Wu, Hua-Tao; Ma, Tao; Liu, Wei-Juan; He, Xue-Jun

    2009-07-01

    The purpose of this study was to investigate the immune and antioxidant activities of Glycyrrhiza glabra polysaccharides (GGP) in rats fed high-fat diet. The experiment was performed on four groups of growing Kunming mice. The results of the experiment showed a statistically significant decrease in serum antioxidant enzyme activities in high-fat group. Administration of GGP dose-dependently significantly enhanced immune and antioxidant enzyme activities in the GGP-treated mice compared to the high-fat model mice. It is concluded that GGP treatment can enhance immune activities, and reduce oxidative stress in high-fat mice.

  18. The effects of chromium complex and level on glucose metabolism and memory acquisition in rats fed high-fat diet.

    PubMed

    Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Agca, Can A; Sahin, Nurhan; Guvenc, Mehmet; Krejpcio, Zbigniew; Staniek, Halina; Hayirli, Armagan

    2011-11-01

    Conditions in which glucose metabolism is impaired due to insulin resistance are associated with memory impairment. It was hypothesized that supplemental chromium (Cr) may alleviate insulin resistance in type 2 diabetes and consequently improve memory acquisition, depending upon its source and level. In a complete randomized design experiment, male Wistar rats (n=60; weighing 200-220 g) were fed either normal (8%, normal diet (ND)) or high-fat (40%, high-fat diet (HFD)) diet and supplemented with Cr as either chromium-glycinate (CrGly) or chromium-acetate (CrAc) at doses of 0, 40, or 80 μg/kg body weight (BW) via drinking water from 8 to 20 weeks of age. Feeding HFD induced type 2 diabetes, as reflected by greater glucose/insulin ratio (2.98 vs. 2.74) comparing to feeding ND. Moreover, HFD rats had greater BW (314 vs. 279 g) and less serum (53 vs. 68 μg/L) and brain (14 vs. 24 ng/g) Cr concentrations than ND rats. High-fat diet caused a 32% reduction in expressions of glucose transporters 1 and 3 (GLUTs) in brain tissue and a 27% reduction in mean percentage time spent in the target quadrant and a 38% increase in spatial memory acquisition phase (SMAP) compared with ND. Compared with supplemental Cr as CrAc, CrGly was more effective to ameliorate response variables (i.e., restoration of tissue Cr concentration, enhancement of cerebral GLUTs expressions, and reduction of the glucose/insulin ratio and SMAP) in a dose-response manner, especially in rats fed HFD. Supplemental Cr as CrGly may have therapeutic potential to enhance insulin action and alleviate memory acquisition in a dose-dependent manner, through restoring tissue Cr reserve and enhancing cerebral GLUTs expressions.

  19. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    PubMed

    Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  20. Red Blood Cell Dysfunction Induced by High-Fat Diet

    PubMed Central

    Unruh, Dusten; Srinivasan, Ramprasad; Benson, Tyler; Haigh, Stephen; Coyle, Danielle; Batra, Neil; Keil, Ryan; Sturm, Robert; Blanco, Victor; Palascak, Mary; Franco, Robert S.; Tong, Wilson; Chatterjee, Tapan; Hui, David Y.; Davidson, W. Sean; Aronow, Bruce J.; Kalfa, Theodosia; Manka, David; Peairs, Abigail; Blomkalns, Andra; Fulton, David J.; Brittain, Julia E.; Weintraub, Neal L.; Bogdanov, Vladimir Y.

    2015-01-01

    Background High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC). Methods and Results A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC−/− mice. In RBCs from HFD-fed wild-type and DARC−/− mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation. Conclusions RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic. PMID:26467254

  1. High fat diet enhances stemness and tumorigenicity of intestinal progenitors

    PubMed Central

    Beyaz, Semir; Mana, Miyeko D.; Roper, Jatin; Kedrin, Dmitriy; Saadatpour, Assieh; Hong, Sue-Jean; Bauer-Rowe, Khristian E.; Xifaras, Michael E.; Akkad, Adam; Arias, Erika; Pinello, Luca; Katz, Yarden; Shinagare, Shweta; Abu-Remaileh, Monther; Mihaylova, Maria M.; Lamming, Dudley W.; Dogum, Rizkullah; Guo, Guoji; Bell, George W.; Selig, Martin; Nielsen, G. Petur; Gupta, Nitin; Ferrone, Cristina R.; Deshpande, Vikram; Yuan, Guo-Cheng; Orkin, Stuart H.; Sabatini, David M.; Yilmaz, Ömer H.

    2016-01-01

    Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors. PMID:26935695

  2. Serotonin Improves High Fat Diet Induced Obesity in Mice

    PubMed Central

    Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T.; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle. PMID:26766570

  3. Curcumin ameliorates high-fat diet-induced spermatogenesis dysfunction

    PubMed Central

    Mu, Yang; Yan, Wen-Jie; Yin, Tai-Lang; Yang, Jing

    2016-01-01

    Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti-inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high-fat diet (HFD)-induced spermatogenesis dysfunction. Sprague-Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B-cell lymphoma (Bcl)-xl, Bcl-associated X protein (Bax) and cleaved-caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved-caspase 3, as well as increased expression of Bcl-xl. In conclusion, the present study revealed that curcumin treatment reduced HFD-induced spermatogenesis dysfunction in male rats. PMID:27600729

  4. Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits.

    PubMed

    Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun

    2014-11-01

    The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals.

  5. Direct effects of fatty meals and adiposity on oxidised low-density lipoprotein.

    PubMed

    Laguna-Camacho, Antonio; Alonso-Barreto, Arely S; Mendieta-Zerón, Hugo

    2015-01-01

    High-fat intake and high adiposity contribute to hyperlipaemia. In a hyperlipaemic state, lipoproteins infiltrate arterial wall where they are modified and cause an immune response characteristic of atherosclerosis. A small fraction of modified lipoproteins including oxidised low-density lipoprotein (ox-LDL) returns to circulation. The present study tracked high-fat meals during four weeks as to find effects of sustained frequency change on adiposity and ox-LDL. The findings indicated that changes in frequency of consumption of high-fat eating episodes correlated directly with changes in adiposity and ox-LDL. Hence the number of fatty meals consumed by people with overweight or obesity in few weeks could affect the atherogenic process.

  6. High-Fat Diet–Induced Retinal Dysfunction

    PubMed Central

    Chang, Richard Cheng-An; Shi, Liheng; Huang, Cathy Chia-Yu; Kim, Andy Jeesu; Ko, Michael L.; Zhou, Beiyan; Ko, Gladys Y.-P.

    2015-01-01

    Purpose. The purpose of this study was to investigate the impact of obesity-induced prediabetes/early diabetes on the retina to provide new evidence on the pathogenesis of type 2 diabetes–associated diabetic retinopathy (DR). Methods. A high-fat diet (HFD)–induced obesity mouse model (male C57BL/6J) was used in this study. At the end of the 12-week HFD feeding regimen, mice were evaluated for glucose and insulin tolerance, and retinal light responses were recorded by electroretinogram (ERG). Western immunoblot and immunohistochemical staining were used to determine changes in elements regulating calcium homeostasis between HFD and control retinas, as well as unstained human retinal sections from DR patients and age-appropriate controls. Results. Compared to the control, the scotopic and photopic ERGs from HFD mice were decreased. There were significant decreases in molecules related to cell signaling, calcium homeostasis, and glucose metabolism from HFD retinas, including phosphorylated protein kinase B (pAKT), glucose transporter 4, L-type voltage-gated calcium channel (L-VGCC), and plasma membrane calcium ATPase (PMCA). Similar changes for pAKT, PMCA, and L-VGCC were also observed in human retinal sections from DR patients. Conclusions. Obesity-induced hyperglycemic and prediabetic/early diabetic conditions caused detrimental impacts on retinal light sensitivities and health. The decrease of the ERG components in early diabetes reflects the decreased neuronal activity of retinal light responses, which may be caused by a decrease in neuronal calcium signaling. Since PI3K-AKT is important in regulating calcium homeostasis and neural survival, maintaining proper PI3K-AKT signaling in early diabetes or at the prediabetic stage might be a new strategy for DR prevention. PMID:25788653

  7. Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals; our lab has demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against put...

  8. Time-restricted feeding reduces adiposity in mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disruption of the circadian rhythm contributes to obesity. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity in male C57BL/6 mice. Three-week-old mice were fed a low-fat or high-fat diet (16% or 45% of energy from corn oil) ad libitum (ad l...

  9. You Are What You Eat: Linking High-Fat Diet to Stem Cell Dysfunction and Tumorigenesis.

    PubMed

    Haller, Samantha; Jasper, Heinrich

    2016-05-05

    A high-fat diet is linked to elevated cancer risk, yet this link remains poorly understood. New studies in mice are now beginning to obtain mechanistic insight into how high-fat diets perturb stem cell function and cause cancers.

  10. What causes high fat diet-induced postprandial inflammation: endotoxin or free fatty acids?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction High fat (saturated fat) diet has been generally used to induce tissue inflammation, insulin resistance and obesity in animal models. High fat diet can also induce postprandial inflammation in humans. Importantly, postprandial inflammation is linked to elevated cardiovascular and metabo...

  11. High protein high fibre snack bars reduce food intake and improve short term glucose and insulin profiles compared with high fat snack bars.

    PubMed

    Williams, Gemma; Noakes, Manny; Keogh, Jennifer; Foster, Paul; Clifton, Peter

    2006-01-01

    The replacement in the diet of refined carbohydrate and fat with fibre and protein has been shown to promote satiety and improve glucose and insulin profiles. It is less clear whether the macronutrient composition of individual foods such as snacks have any meaningful impact on metabolic parameters and satiety. We examined if the consumption of higher protein higher fibre snack bars would result in reducing outcome measures such as food intake and glucose and insulin patterns compared to a conventional isocaloric high fat high refined carbohydrate snack bar. Twenty three women were randomized in a single blind cross over study with 2 interventions, a high fat high sugar snack bar and a comparatively higher protein, higher fibre snack bar intervention. Snack bars were eaten at mid morning and mid afternoon, and a standard breakfast and ad libitum buffet lunch. The glucose and insulin responses over 9 hours were significantly lower (P = 0.014 and P = 0.012 respectively) during the high protein snack bar intervention. Peak glucose levels were also 16% lower after the morning HP bar (P <0.001). The morning high protein bar reduced the energy intake at the buffet lunch meal by 5% (4657 +/- 1025KJ vs 4901 +/- 1186KJ, P < 0.05). Altering the macronutrient composition of a snack bar can assist in reducing the energy intake at a subsequent meal and improve short term glucose and insulin profiles.

  12. Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

    PubMed Central

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

    2012-01-01

    We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

  13. A Lipoprotein Lipase–Promoting Agent, NO-1886, Improves Glucose and Lipid Metabolism in High Fat, High Sucrose–Fed New Zealand White Rabbits

    PubMed Central

    Yuan, Zhonghua; Tsutsumi, Kazuhiko; Xie, Yuxiang; Zhang, Qiuju; Wang, Zongbao; fu, Guoxiang; Long, Guang; Yang, Yongzong

    2003-01-01

    The synthetic compound NO-1886 is a lipoprotein lipase activator that lowers plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C). Recently, the authors found that NO-1886 also had an action of reducing plasma glucose in high-fat/high-sucrose diet–induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on insulin resistance and β-cell function in rabbits. Our results showed that high-fat/high-sucrose feeding increased plasma triglyceride, free fatty acid (FFA), and glucose levels and decreased HDL-C level. This diet also induced insulin resistance and impairment of acute insulin response to glucose loading. Supplementing 1% NO-1886 into the high-fat/high-sucrose diet resulted in decreased plasma triglyceride, FFA, and glucose levels and increased HDL-C level. The authors also found a clear increased glucose clearance and a protected acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 suppresses the elevation of blood glucose in rabbits induced by feeding a high-fat/high-sucrose diet, probably through controlling lipid metabolism and improving insulin resistance. PMID:12745668

  14. Maternal high-fat diet programming of the neuroendocrine system and behavior.

    PubMed

    Sullivan, Elinor L; Riper, Kellie M; Lockard, Rachel; Valleau, Jeanette C

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic-pituitary-adrenal (HPA) axis.

  15. Maternal High-Fat Diet Programming of the Neuroendocrine System and Behavior

    PubMed Central

    Sullivan, Elinor L.; Riper, Kellie M.; Lockard, Rachel; Valleau, Jeanette C.

    2015-01-01

    Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic pituitary adrenal (HPA) axis. PMID:25913366

  16. High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22

    PubMed Central

    Gulhane, Max; Murray, Lydia; Lourie, Rohan; Tong, Hui; Sheng, Yong H.; Wang, Ran; Kang, Alicia; Schreiber, Veronika; Wong, Kuan Yau; Magor, Graham; Denman, Stuart; Begun, Jakob; Florin, Timothy H.; Perkins, Andrew; Cuív, Páraic Ó.; McGuckin, Michael A.; Hasnain, Sumaira Z.

    2016-01-01

    Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy. PMID:27350069

  17. Green tea extract improves high fat diet-induced hypothalamic inflammation, without affecting the serotoninergic system.

    PubMed

    Okuda, Marcos H; Zemdegs, Juliane C S; de Santana, Aline A; Santamarina, Aline B; Moreno, Mayara F; Hachul, Ana C L; dos Santos, Bruno; do Nascimento, Claudia M Oller; Ribeiro, Eliane B; Oyama, Lila M

    2014-10-01

    To investigate possible mechanisms of green tea's anti-obesity and anti-diabetic effects in the hypothalamus, the central regulator of metabolism, of mice fed with high-fat diet (HFD), we analyzed proteins of the toll-like receptor 4 (TLR4) pathway and serotoninergic proteins involved in energy homeostasis. Thirty-day-old male Swiss mice were fed with HFD rich in saturated fat and green tea extract (GTE) for 8 weeks. After that, body weight and mass of fat depots were evaluated. Oral glucose tolerance test was performed 3 days prior to euthanasia; serum glucose, insulin and adiponectin were measured in fasted mice. Hypothalamic TLR4 pathway proteins, serotonin receptors 1B and 2C and serotonin transporter were analyzed by Western blotting or enzyme-linked immunosorbent assay. A second set of animals was used to measure food intake in response to fluoxetine, a selective serotonin reuptake inhibitor. Mice fed with HFD had increased body weight and mass of fat depots, impaired oral glucose tolerance, elevated glucose and insulin and decreased adiponectin serum levels. TLR4, IκB-α, nuclear factor κB p50 and interleukin 6 were increased by HFD. Concomitant GTE treatment ameliorated these parameters. The serotoninergic system remained functional after HFD treatment despite a few alterations in protein content of serotonin receptors 1B and 2C and serotonin transporter. In summary, the GTE attenuated the deleterious effects of the HFD investigated in this study, partially due to reduced hypothalamic inflammation.

  18. CMKLR1 deficiency influences glucose tolerance and thermogenesis in mice on high fat diet.

    PubMed

    Huang, Chen; Wang, Miaomiao; Ren, Lirong; Xiang, Liang; Chen, Jie; Li, Mengxia; Xiao, Tianxia; Ren, Peigen; Xiong, Likuan; Zhang, Jian V

    2016-04-29

    Obesity has become a global epidemic disease, contributing to increases in the prevalence of type 2 diabetes. CMKLR1, one of the receptors for chemerin, has a wide range of functions in physiological and pathological activity, including innate and adaptive immunity, inflammation, metabolism and reproduction. In our study, CMKLR1 deficiency did not influence the gain of body weight but did exacerbate glucose intolerance, increase serum insulin level, and promote insulin resistance in mice on high fat diets. The expression of thermogenesis related genes was examined and indicated to decrease in CMKLR1 knockout (KO) mice in both normal and cold environments, which indicated CMKLR1 influence the thermogenesis process. Cold exposure induced significant body mass decrease and improved glucose tolerance and insulin resistance in wild type HFD mice but had no obvious effect on CMKLR1 KO HFD mice. In vitro, loss of CMKLR1 did not significantly influence the differentiation of stromal vascular fibroblasts (SVFs) derived from adipose tissue, but did suppress the expression of thermogenesis related genes. Collectively, these data demonstrate that CMKLR1 deficiency induces inbalance of glucose metabolism and impairs the cold induced-thermogenesis process in high diet models.

  19. Gomisin N inhibits adipogenesis and prevents high-fat diet-induced obesity

    PubMed Central

    Jang, Min-Kyung; Yun, Ye-Rang; Kim, Ji-Hyun; Park, Mi-Hee; Jung, Myeong Ho

    2017-01-01

    Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition. GN inhibited the extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B signaling in the MCE process and activated AMP-activated protein kinase. Furthermore, GN downregulated CCAT/enhancer-binding protein β (C/EBPβ) and histone H3K9 demethylase JMJD2B during early stages of adipogenesis, and therefore repressed the expression of C/EBPβ-targeted cell cycle genes. In addition, GN also repressed the expression of histone H3K4 methyltransferase MLL4 and reduced PPARγ expression. Moreover, GN effectively lowered the final body weight, adipose tissue mass, and reduced the serum levels of glucose, total triglyceride, and cholesterol in the HFD-induced obese mice. GN also markedly reduced hepatic triglyceride level induced by HFD. Collectively, these findings suggest that GN has potential as a novel agent for the prevention and treatment of obesity. PMID:28067305

  20. Switching Adolescent High-Fat Diet to Adult Control Diet Restores Neurocognitive Alterations

    PubMed Central

    Boitard, Chloé; Parkes, Shauna L.; Cavaroc, Amandine; Tantot, Frédéric; Castanon, Nathalie; Layé, Sophie; Tronel, Sophie; Pacheco-Lopez, Gustavo; Coutureau, Etienne; Ferreira, Guillaume

    2016-01-01

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala) and for the hypothalamic-pituitary-adrenal (HPA) stress axis, which is required for cognitive and emotional processing. We recently demonstrated that adolescent, but not adult, high-fat diet (HF) exposure leads to impaired hippocampal function and enhanced amygdala function through HPA axis alteration (Boitard et al., 2012, 2014, 2015). Here, we assessed whether the effects of adolescent HF consumption on brain function are permanent or reversible. After adolescent exposure to HF, switching to a standard control diet restored levels of hippocampal neurogenesis and normalized enhanced HPA axis reactivity, amygdala activity and avoidance memory. Therefore, while the adolescent period is highly vulnerable to the deleterious effects of diet-induced obesity, adult exposure to a standard diet appears sufficient to reverse alterations of brain function. PMID:27917115

  1. Endothelium-Specific Interference with PPARγ Causes Cerebral Vascular Dysfunction in Response to a High Fat Diet

    PubMed Central

    Beyer, Andreas M.; de Lange, Willem J.; Halabi, Carmen M.; Modrick, Mary L.; Keen, Henry L.; Faraci, Frank M.; Sigmund, Curt D.

    2008-01-01

    The ligand-activated transcription factor PPARγ is expressed in vascular endothelium where it exerts anti-inflammatory and anti-oxidant effects. However, its role in regulating vascular function remains undefined. We examined endothelial function in transgenic mice expressing dominant negative mutants of PPARγ under the control of an endothelial-specific promoter to test the hypothesis that endothelial PPARγ plays a protective role in the vasculature. Under baseline conditions, responses to the endothelium-dependent agonist acetylcholine (Ach) were not affected in either aorta or the basilar artery in vitro. In response to feeding a high fat diet for 12 weeks, Ach produced dilation that was markedly impaired in the basilar artery of mice expressing dominant negative mutants, but not in mice expressing wildtype PPARγ controlled by the same promoter. Unlike basilar artery, 12 weeks of high fat diet was not sufficient to cause endothelial dysfunction in the aorta of mice expressing dominant negative PPARγ, although it became evident after 25 weeks. The responses to Ach in basilar artery were restored to normal after treatment with a scavenger of superoxide. Baseline blood pressure was only slightly elevated in the transgenic mice, but the pressor response to angiotensin-II was augmented. Thus, interference with PPARγ in the endothelium produces endothelial dysfunction in the cerebral circulation via a mechanism involving oxidative stress. Consistent with its role as a fatty acid sensor, these findings provide genetic evidence that endothelial PPARγ plays a critical role in protecting a range of blood vessels in response to a high fat diet. PMID:18676352

  2. Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring.

    PubMed

    Hawkes, Cheryl A; Gentleman, Steve M; Nicoll, James Ar; Carare, Roxana O

    2015-03-01

    Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides in the extracellular spaces of the brain as plaques and in the walls of blood vessels as cerebral amyloid angiopathy (CAA). Failure of perivascular drainage of Aβ along cerebrovascular basement membranes contributes to the development of CAA. Mid-life hypercholesterolaemia is a risk factor for the development of AD. Maternal obesity is associated with the development of obesity, hypertension and hypercholesterolaemia in adulthood, suggesting that the risk for AD and CAA may also be influenced by the early-life environment. In the present study, we tested the hypothesis that early-life exposure to a high-fat diet results in changes to the cerebrovasculature and failure of Aβ clearance from the brain. We also assessed whether vascular Aβ deposition is greater in the brains of aged humans with a history of hyperlipidaemia, compared to age-matched controls with normal lipidaemia. Using a mouse model of maternal obesity, we found that exposure to a high-fat diet during gestation and lactation induced changes in multiple components of the neurovascular unit, including a down-regulation in collagen IV, fibronectin and apolipoprotein E, an up-regulation in markers of astrocytes and perivascular macrophages and altered blood vessel morphology in the brains of adult mice. Sustained high-fat diet over the entire lifespan resulted in additional decreases in levels of pericytes and impaired perivascular clearance of Aβ from the brain. In humans, vascular Aβ load was significantly increased in the brains of aged individuals with a history of hypercholesterolaemia. These results support a critical role for early dietary influence on the brain vasculature across the lifespan, with consequences for the development of age-related cerebrovascular and neurodegenerative diseases.

  3. Inulin oligofructose attenuates metabolic syndrome in high-carbohydrate, high-fat diet-fed rats.

    PubMed

    Kumar, Senthil A; Ward, Leigh C; Brown, Lindsay

    2016-11-01

    Prebiotics alter bacterial content in the colon, and therefore could be useful for obesity management. We investigated the changes following addition of inulin oligofructose (IO) in the food of rats fed either a corn starch (C) diet or a high-carbohydrate, high-fat (H) diet as a model of diet-induced metabolic syndrome. IO did not affect food intake, but reduced body weight gain by 5·3 and 12·3 % in corn starch+inulin oligofructose (CIO) and high-carbohydrate, high-fat with inulin oligofructose (HIO) rats, respectively. IO reduced plasma concentrations of free fatty acids by 26·2 % and TAG by 75·8 % in HIO rats. IO increased faecal output by 93·2 %, faecal lipid excretion by 37·9 % and weight of caecum by 23·4 % and colon by 41·5 % in HIO rats. IO improved ileal morphology by reducing inflammation and improving the density of crypt cells in HIO rats. IO attenuated H diet-induced increases in abdominal fat pads (C 275 (sem 19), CIO 264 (sem 40), H 688 (sem 55), HIO 419 (sem 32) mg/mm tibial length), fasting blood glucose concentrations (C 4·5 (sem 0·1), CIO 4·2 (sem 0·1), H 5·2 (sem 0·1), HIO 4·3 (sem 0·1) mmol/l), systolic blood pressure (C 124 (sem 2), CIO 118 (sem 2), H 152 (sem 2), HIO 123 (sem 3) mmHg), left ventricular diastolic stiffness (C 22·9 (sem 0·6), CIO 22·9 (sem 0·5), H 27·8 (sem 0·5), HIO 22·6 (sem 1·2)) and plasma alanine transaminase (C 29·6 (sem 2·8), CIO 32·1 (sem 3·0), H 43·9 (sem 2·6), HIO 33·6 (sem 2·0) U/l). IO attenuated H-induced increases in inflammatory cell infiltration in the heart and liver, lipid droplets in the liver and plasma lipids as well as impaired glucose and insulin tolerance. These results suggest that increasing soluble fibre intake with IO improves signs of the metabolic syndrome by decreasing gastrointestinal carbohydrate and lipid uptake.

  4. Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice.

    PubMed

    Lima, Leandro Ceotto Freitas; Saliba, Soraya Wilke; Andrade, João Marcus Oliveira; Cunha, Maria Luisa; Cassini-Vieira, Puebla; Feltenberger, John David; Barcelos, Lucíola Silva; Guimarães, André Luiz Sena; de-Paula, Alfredo Mauricio Batista; de Oliveira, Antônio Carlos Pinheiro; Santos, Sérgio Henrique Sousa

    2016-05-16

    Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

  5. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.

  6. Rat Models of Diet-Induced Obesity and High Fat/Low Dose Streptozotocin Type 2 Diabetes: Effect of Reversal of High Fat Diet Compared to Treatment with Enalapril or Menhaden Oil on Glucose Utilization and Neuropathic Endpoints.

    PubMed

    Holmes, Amey; Coppey, Lawrence J; Davidson, Eric P; Yorek, Mark A

    2015-01-01

    We examined whether reversal of high fat diet, stimulating weight loss, compared to two treatments previously shown to have beneficial effects, could improve glucose utilization and peripheral neuropathy in animal models of obesity and type 2 diabetes. Rats were fed a high fat diet and treated with a low dose of streptozotocin to create models of diet induced obesity or type 2 diabetes, respectively. Afterwards, rats were transferred to a normal diet or treated with enalapril or dietary enrichment with menhaden oil for 12 weeks. Obesity and to a greater extent type 2 diabetes were associated with impaired glucose utilization and peripheral neuropathy. Placing obese rats on a normal diet improved glucose utilization. Steatosis but not peripheral neuropathy was improved after placing obese or diabetic rats on a normal diet. Treating obese and diabetic rats with enalapril or a menhaden oil enriched diet generally improved peripheral neuropathy endpoints. In summary, dietary improvement with weight loss in obese or type 2 diabetic rats was not sufficient to correct peripheral neuropathy. These results further stress the need for discovery of a comprehensive treatment for peripheral neuropathy.

  7. High fat diet promotes achievement of peak bone mass in young rats

    SciTech Connect

    Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T.; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R.; Bhat, Manoj Kumar

    2014-12-05

    Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

  8. Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo.

    PubMed

    Wessels, Bart; van den Broek, Nicole M A; Ciapaite, Jolita; Houten, Sander M; Wanders, Ronald J A; Nicolay, Klaas; Prompers, Jeanine J

    2015-10-01

    Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1) L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle lipid status was determined by (1)H MRS (intramyocellular lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced insulin resistance and was associated with decreases in muscle and blood free carnitine, elevated levels of muscle lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free carnitine content, carnitine supplementation did not induce improvements in muscle lipid status, in vivo mitochondrial function, or insulin sensitivity. Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle mitochondrial dysfunction in vivo.

  9. Maternal high-fat diet is associated with impaired fetal lung development.

    PubMed

    Mayor, Reina S; Finch, Katelyn E; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D; Frank, Aaron P; Hahner, Lisa D; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F; Rosenfeld, Charles R; Savani, Rashmin C; Clegg, Deborah J

    2015-08-15

    Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development.

  10. Transcriptome analysis of the effects of chitosan on the hyperlipidemia and oxidative stress in high-fat diet fed mice.

    PubMed

    Wang, Bin; Zhang, Sicong; Wang, Xiaoya; Yang, Shuo; Jiang, Qixing; Xu, Yanshun; Xia, Wenshui

    2017-04-03

    Transcriptome analysis was performed to investigate the alterations in gene expression after chitosan (CS) treatment on the liver of mice fed with high-fat diet (HFD). The results showed that the body weight, the liver weight and the epididymal fat mass of HFD mice, which were 62.98%, 46.51% and 239.37%, respectively, higher than those of control mice, could be significantly decreased by chitosan supplementation. Also, high-fat diet increased both plasma lipid and liver lipid as compared with the control mice. Chitosan supplementation decreased the plasma lipid and liver lipid, increased the lipoprotein lipase (LPL) and hepatic lipase (HL) activity, increased T-AOC and decreased MDA in the liver and the epididymis adipose as compared with the HFD mice. Transcriptome analysis indicated that increased Mups, Lcn2, Gstm3 and CYP2E1 expressions clearly indicated HFD induced lipid metabolism disorder and oxidative damage. Especially, chitosan treatment decreased the Mup17 and Lcn2 expressions by 64.32% and 82.43% respectively as compared with those of HFD mice. These results indicated that chitosan possess the ability to improve the impairment of lipid metabolism as strongly associated with increased Mups expressions and gene expressions related to oxidative stress.

  11. Effects of diurnal variation of gut microbes and high fat feeding on host circadian clock function and metabolism

    PubMed Central

    Leone, Vanessa; Gibbons, Sean M.; Martinez, Kristina; Hutchison, Alan L.; Huang, Edmond Y.; Cham, Candace M.; Pierre, Joseph F.; Heneghan, Aaron F.; Nadimpalli, Anuradha; Hubert, Nathaniel; Zale, Elizabeth; Wang, Yunwei; Huang, Yong; Theriault, Betty; Dinner, Aaron R.; Musch, Mark W.; Kudsk, Kenneth A.; Prendergast, Brian J.; Gilbert, Jack A.; Chang, Eugene B.

    2015-01-01

    SUMMARY Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally-raised counterparts. Examination of gut microbiota in conventionally-raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low or high fat feeding, particularly short chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially-derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet. PMID:25891358

  12. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    PubMed

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  13. Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers.

    PubMed

    Zvada, Simbarashe P; Van Der Walt, Jan-Stefan; Smith, Peter J; Fourie, P Bernard; Roscigno, Giorgio; Mitchison, Denis; Simonsson, Ulrika S H; McIlleron, Helen M

    2010-08-01

    Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches.

  14. Effects of Four Different Meal Types on the Population Pharmacokinetics of Single-Dose Rifapentine in Healthy Male Volunteers▿

    PubMed Central

    Zvada, Simbarashe P.; Van Der Walt, Jan-Stefan; Smith, Peter J.; Fourie, P. Bernard; Roscigno, Giorgio; Mitchison, Denis; Simonsson, Ulrika S. H.; McIlleron, Helen M.

    2010-01-01

    Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches. PMID:20516273

  15. The nutritional content and cost of supermarket ready-meals. Cross-sectional analysis☆

    PubMed Central

    Remnant, Jennifer; Adams, Jean

    2015-01-01

    Background: Over-reliance on convenience foods, including ready-meals, has been suggested as one contributor to obesity. Little research has systematically explored the nutritional content of supermarket ready-meals. We described the nutritional content and cost of UK supermarket ready-meals. Methods: We conducted a survey of supermarket own-brand chilled and frozen ready-meals available in branches of ten national supermarket chains in one city in northern England. Data on price, weight and nutritional content of meals in four ranges (‘healthier’, luxury, economy and standard) and of six types (macaroni cheese, meat lasagne, cottage pie, chicken tikka masala, fish pie, and sweet and sour chicken) were collected. Nutritional content was compared to ranges used to identify low, medium and high fat, saturated fat, sugar and salt in nationally recommended front-of-pack labelling. Results: 166 ready-meals were included from 41 stores. Overall, ready-meals were high in saturated fat and salt, and low in sugar. One-fifth of meals were low in fat, saturated fat, salt and sugar, including two-thirds of ‘healthier’ meals. Meals that were low for three out of the four front-of-pack nutrients were the cheapest. Conclusions: Supermarket ready-meals do not have a healthful nutritional profile overall. However, a number of healthier meals were available – particularly amongst meals specifically marked as ‘healthier’. There was little evidence that healthier meals necessarily cost more. Further effort is required to encourage producers to improve the nutritional profile of the full range of ready-meals, and not just those specifically labelled as ‘healthier’. PMID:25963106

  16. High-fat diet alters the dopamine and opioid systems: effects across development

    PubMed Central

    Reyes, T M

    2012-01-01

    Consumption of a high-fat diet has been linked to obesity, dyslipidemia and cardiovascular disease. Less well appreciated are adverse effects on the brain and behavior. Recent research has shown that consumption of a high-fat diet can alter gene expression within the brain, and the dopamine and opioid neurotransmitter systems appear to be vulnerable to dysregulation. This review will focus on recent reports in both humans and animal models that describe adverse effects of high-fat diet consumption on the central reward circuitry. In addition, the importance of different development windows will be discussed, with effects observed in both the prenatal/perinatal time period and with chronic high-fat diet consumption in adulthood. PMID:27152150

  17. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It was investigated the preventive effects of the flavanones hesperidin, eriocitrin and eriodictyol on the oxidative stress and systemic inflammation induced by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high fat diet ...

  18. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters.

    PubMed

    Lin, Yi-Ling; Chang, Yuan-Yen; Yang, Deng-Jye; Tzang, Bor-Show; Chen, Yi-Chen

    2013-09-01

    Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids. To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets. Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9 mL NJ/kg BW, respectively. After a 6-week feeding period, the increased (p<0.05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p<0.05) by NJ supplementation. NJ also decreased (p<0.05) serum/liver lipids but enhanced (p<0.05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters. High-fat dietary hamsters supplemented with NJ had higher (p<0.05) liver antioxidant capacities but lowered (p<0.05) liver iNOS, COX-2, TNF-α, and IL-1β expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ. Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses.

  19. Coacervate whey protein improves inflammatory milieu in mice fed with high-fat diet

    PubMed Central

    2014-01-01

    Background Functional foods with bioactive properties may help in treat obesity, as they can lead to a decreased risks of inflammatory diseases. The aim of this study was to investigate the effects of chitosan coacervate whey protein on the proinflammatory processes in mice fed with high-fat diet. Methods Mice were divided into two groups receiving either a normolipidic or high-fat diet; the animals in each of the two diet groups were given a diet supplement of either coacervate (gavage, 36 mg protein/kg of body weight) or tap water for four weeks [groups: normolipidic diet plus water (C); normolipidic diet and coacervate (CC); high-fat diet and water (H); and high-fat diet and coacervate (HC)]. Results The high-fat diet promoted inflammation, possibly by decreased adiponectin/sum of adipose tissues ratio and increased phosphorylation of NF-κB p50. In HC we observed a positive correlation between IL-10 and TNF-α in mesenteric adipose tissue, retroperitoneal adipose tissue and liver tissue. We also observed a positive correlation between lipopolisaccharide with IL-10 in the liver tissue. Conclusions High-fat diet treatment promoted metabolic alterations and inflammation, and chitosan coacervate whey protein modulated inflammatory milieu. PMID:24673809

  20. Protective effect of Caralluma fimbriata against high-fat diet induced testicular oxidative stress in rats.

    PubMed

    Gujjala, Sudhakara; Putakala, Mallaiah; Gangarapu, Venkatanarayana; Nukala, Srinivasulu; Bellamkonda, Ramesh; Ramaswamy, Rajendran; Desireddy, Saralakumari

    2016-10-01

    High-fat diet (HFD) promotes the oxidative stress formation, which in turn has hazardous effects on reproductive system and fertility. The objective of this study was to evaluate the protective effect of Caralluma fimbriata on high-fat diet-induced oxidative stress in the testis of rat. Male Wistar rats were randomly divided into five groups: Control (C), Control treated with CFE (C+ CFE), High fat diet fed (HFD), High fat diet fed treated with CFE (HFD+CFE) and High fat diet fed treated with Metformin (HFD+Met). CFE was orally administered (200mg/kg body weight) for 90days to groups-C+CFE and HFD+CFE rats. The effects of HF-diet on the reproductive organs were determined by measuring relative and absolute testes and epididymal fat pads weights. Regarding testes antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation, polyol pathway enzymes and lower GSH levels and lower activities of antioxidants, while CFE treatment prevented all these observed abnormalities. The present study clearly indicates that CFE offers a significant protection against HF-diet induced testicular oxidative stress in rats.

  1. Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: A randomized controlled trial

    PubMed Central

    Koopman, Karin E; Caan, Matthan WA; Nederveen, Aart J; Pels, Anouk; Ackermans, Mariette T; Fliers, Eric; la Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    American children consume up to 27% of calories from high-fat and high-sugar snacks. Both sugar and fat consumption have been implicated as a cause of hepatic steatosis and obesity but the effect of meal pattern is largely understudied. We hypothesized that a high meal frequency, compared to consuming large meals, is detrimental in the accumulation of intrahepatic and abdominal fat. To test this hypothesis, we randomized 36 lean, healthy men to a 40% hypercaloric diet for 6 weeks or a eucaloric control diet and measured intrahepatic triglyceride content (IHTG) using proton magnetic resonance spectroscopy (1H-MRS), abdominal fat using magnetic resonance imaging (MRI), and insulin sensitivity using a hyperinsulinemic euglycemic clamp with a glucose isotope tracer before and after the diet intervention. The caloric surplus consisted of fat and sugar (high-fat-high-sugar; HFHS) or sugar only (high-sugar; HS) and was consumed together with, or between, the three main meals, thereby increasing meal size or meal frequency. All hypercaloric diets similarly increased body mass index (BMI). Increasing meal frequency significantly increased IHTG (HFHS mean relative increase of 45%; P = 0.016 and HS mean relative increase of 110%; P = 0.047), whereas increasing meal size did not (2-way analysis of variance [ANOVA] size versus frequency P = 0.03). Abdominal fat increased in the HFHS-frequency group (+63.3 ± 42.8 mL; P = 0.004) and tended to increase in the HS-frequency group (+46.5 ± 50.7 mL; P = 0.08). Hepatic insulin sensitivity tended to decrease in the HFHS-frequency group while peripheral insulin sensitivity was not affected. Conclusion: A hypercaloric diet with high meal frequency increased IHTG and abdominal fat independent of caloric content and body weight gain, whereas increasing meal size did not. This study suggests that snacking, a common feature in the Western diet, independently contributes to hepatic steatosis and obesity. (Trial

  2. Chronic rhein treatment improves recognition memory in high-fat diet-induced obese male mice.

    PubMed

    Wang, Sen; Huang, Xu-Feng; Zhang, Peng; Wang, Hongqin; Zhang, Qingsheng; Yu, Shijia; Yu, Yinghua

    2016-10-01

    High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation.

  3. GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet.

    PubMed

    Baldassano, Sara; Rappa, Francesca; Amato, Antonella; Cappello, Francesco; Mulè, Flavia

    2015-12-01

    Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to dietary nutrients, which acts through a specific receptor, the GLP-2 receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving also the intestinal adaptation to high fat diet (HFD). In consideration of the well-known relationship between chronic HFD and impaired glucose metabolism, in the present study we examined if the blocking of the GLP-2 signaling by chronic treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional consequences in the regulation of glucose metabolism in HFD-fed mice. Compared with animals fed standard diet (STD), mice at the 10th week of HFD showed hyperglycaemia, glucose intolerance, high plasma insulin level after glucose load, increased pancreas weight and β cell expansion, but not insulin resistance. In HFD fed mice, GLP-2 (3-33) treatment for 4 weeks (from the 6th to the 10th week of diet) did not affect fasting glycaemia, but it significantly increased the glucose intolerance, both fasting and glucose-induced insulin levels, and reduced the sensitivity to insulin leading to insulin-resistance. In GLP-2 (3-33)-treated HFD mice pancreas was significantly heavier and displayed a significant increase in β-cell mass in comparison with vehicle-treated HFD mice. In STD mice, the GLP-2 (3-33) treatment did not affect fasted or glucose-stimulated glycemia, insulin, insulin sensitivity, pancreas weight and beta cell mass. The present study suggests that endogenous GLP-2 may act as a protective factor against the dysregulation of the glucose metabolism that occurs in HFD mice, because GLP-2 (3-33) worsens glucose metabolism disorders.

  4. Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation.

    PubMed

    Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J; Ceglia, Lisa; Rasmussen, Helen

    2013-08-01

    It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D [25(OH)D] response to supplemental vitamin D3 . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty-two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal, or low-fat meal; each was given a monthly 50,000 IU vitamin D3 supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D3 was measured by liquid chromatography-mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hour increments in vitamin D3 , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (p = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low-fat meal group.

  5. Programming Effects of Prenatal Glucocorticoid Exposure with a Postnatal High-Fat Diet in Diabetes Mellitus

    PubMed Central

    Sheen, Jiunn-Ming; Hsieh, Chih-Sung; Tain, You-Lin; Li, Shih-Wen; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Miao-Meng; Chen, Yu-Chieh; Huang, Li-Tung

    2016-01-01

    Increasing evidence has shown that many chronic diseases originate from early life, even before birth, through what are termed as fetal programming effects. Glucocorticoids are frequently used prenatally to accelerate the maturation of the lungs of premature infants. High-fat diets are associated with insulin resistance, but the effects of prenatal glucocorticoid exposure plus a postnatal high-fat diet in diabetes mellitus remain unclear. We administered pregnant Sprague-Dawley rats’ intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at gestational days 14–20. Male offspring were administered a normal or high-fat diet starting from weaning. We assessed the effects of prenatal steroid exposure plus postnatal high-fat diet on the liver, pancreas, muscle and fat at postnatal day 120. At 15 and 30 min, sugar levels were higher in the dexamethasone plus high-fat diet (DHF) group than the vehicle plus high-fat diet (VHF) group in the intraperitoneal glucose tolerance test (IPGTT). Serum insulin levels at 15, 30 and 60 min were significantly higher in the VHF group than in the vehicle and normal diet group. Liver insulin receptor and adenosine monophosphate-activated protein kinase mRNA expressions and protein levels were lower in the DHF group. Insulin receptor and insulin receptor substrate-1 mRNA expressions were lower in the epididymal adipose tissue in the VHF and DHF groups. “Programming” of liver or epididymal adipose tissue resulted from prenatal events. Prenatal steroid exposure worsened insulin resistance in animals fed a high-fat diet. PMID:27070590

  6. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m⁶A Modifications in Adipose and Skeletal Muscle Tissues in Offspring.

    PubMed

    Li, Xiao; Yang, Jing; Zhu, Youbo; Liu, Yuan; Shi, Xin'e; Yang, Gongshe

    2016-08-19

    Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m⁶A methylation-an old epigenetic marker receiving increased attention recently-is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee's index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N⁶-methyladenosine (m⁶A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m⁶A modifications at three weeks, and lowered m⁶A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m⁶A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m⁶A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m⁶A system during the transmission from maternal nutrition to subsequent generations.

  7. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

    PubMed Central

    Li, Xiao; Yang, Jing; Zhu, Youbo; Liu, Yuan; Shi, Xin’e; Yang, Gongshe

    2016-01-01

    Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m6A methylation—an old epigenetic marker receiving increased attention recently—is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee’s index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N6-methyladenosine (m6A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m6A modifications at three weeks, and lowered m6A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m6A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m6A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m6A system during the transmission from maternal nutrition to subsequent generations. PMID:27548155

  8. Bolus Estimation—Rethinking the Effect of Meal Fat Content

    PubMed Central

    Laxminarayan, Srinivas; Reifman, Jaques; Edwards, Stephanie S.; Wolpert, Howard

    2015-01-01

    Abstract Background: Traditionally, insulin bolus calculations for managing postprandial glucose levels in individuals with type 1 diabetes rely solely on the carbohydrate content of a meal. However, recent studies have reported that other macronutrients in a meal can alter the insulin required for good postprandial control. Specifically, studies have shown that high-fat (HF) meals require more insulin than low-fat (LF) meals with identical carbohydrate content. Our objective was to assess the mechanisms underlying the higher insulin requirement observed in one of these studies. Materials and Methods: We used a combination of previously validated metabolic models to fit data from a study comparing HF and LF dinners with identical carbohydrate content in seven subjects with type 1 diabetes. For each subject and dinner type, we estimated the model parameters representing the time of peak meal-glucose appearance (τm), insulin sensitivity (SI), the net hepatic glucose balance, and the glucose effect at zero insulin in four time windows (dinner, early night, late night, and breakfast) and assessed the differences in model parameters via paired Wilcoxon signed-rank tests. Results: During the HF meal, the τm was significantly delayed (mean and standard error [SE]: 102 [14] min vs. 71 [4] min; P = 0.02), and SI was significantly lower (7.25 × 10−4 [1.29 × 10−4] mL/μU/min vs. 8.72 × 10−4 [1.08 × 10−4] mL/μU/min; P = 0.02). Conclusions: In addition to considering the putative delay in gastric emptying associated with HF meals, we suggest that clinicians reviewing patient records consider that the fat content of these meals may alter SI. PMID:26270134

  9. Low Carbohydrate/High Fat Diet Attenuates Pressure Overload Induced Ventricular Remodeling and Dysfunction

    PubMed Central

    Duda, Monika K.; O’Shea, Karen M.; Lei, Biao; Barrows, Brian R.; Azimzadeh, Agnes M.; McElfresh, Tracy E.; Hoit, Brian D.; Kop, Willem J.; Stanley, William C.

    2009-01-01

    Background It is not known how carbohydrate and fat intake impact the development of left ventricular (LV) hypertrophy and contractile dysfunction in response to pressure overload. We hypothesized that a low carbohydrate/high fat diet prevents LV hypertrophy and dysfunction compared to high carbohydrate diets. Methods and Results Rats were fed high carbohydrate diets comprised of either starch or sucrose, or a low carbohydrate/high fat diet, and underwent abdominal aortic banding (AAB) for two months. AAB increased LV mass with all diets. LV end diastolic and systolic volumes, and the ratio of the mRNA for myosin heavy chainβ/α were increased with both high carbohydrate diets, but not with the low carbohydrate/high fat diet. Circulating levels of insulin and leptin, both stimulants for cardiac growth, were lower, and free fatty acids higher, with the low carbohydrate/high fat diet compared to high carbohydrate diets. Among AAB animals LV volumes were positively correlated with insulin, and LV mass correlated with leptin. Conclusion A low carbohydrate/high fat diet attenuated pressure overload-induced LV remodeling compared to high carbohydrate diets. This effect corresponded to lower insulin and leptin concentrations, suggesting they may contribute to the development of LV hypertrophy and dysfunction under conditions of pressure overload. PMID:18474346

  10. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet

    PubMed Central

    Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo

    2015-01-01

    In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism. PMID:26301251

  11. Ameliorating effect of Allium Sativum on high-fat diet induced fatty liver in albino rats

    PubMed Central

    Qamar, Aisha; Usmani, Ambreen; Waqar, Humera; Siddiqui, Asma; Kumar, Hemant

    2016-01-01

    Objective: To assess the hepatoprotective effect provided by fresh garlic on fatty liver induced by high-fat diet. Methods: This experimental study was carried out at BMSI, JPMC from October to November 2008. Thirty adult albino rats, 200-240 gram weight, were divided into three groups. Group A received control diet, Group B received high-fat diet (20 mg butter/100 gm diet) and Group C received high-fat diet with fresh garlic (20 mg butter with 6 gm fresh garlic/100 gm diet). The groups were further divided on the basis of duration of treatment, four weeks and eight weeks respectively. The rats were sacrificed, liver removed, weighed and relative liver weight calculated. Hepatic tissue was processed and tissue slides stained with haematoxylin and eosin. Results: There was significant increase in relative liver weight in group B animals as compared to the control animals, which decreased significantly in group C. Haematoxylin and eosin stained sections revealed ballooned hepatocytes having vesicular appearance with pyknotic nuclei in high-fat group which were preserved to a great extent in group C animals. Conclusion: This study has shown that use of fresh garlic along with high-fat diet prevents its damaging effects on liver to a great extent. PMID:27182249

  12. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet.

    PubMed

    Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo

    2015-01-01

    In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism.

  13. Effect of high-fat diet, surrounding temperature, and enterostatin on uncoupling protein gene expression.

    PubMed

    Rippe, C; Berger, K; Böiers, C; Ricquier, D; Erlanson-Albertsson, C

    2000-08-01

    Nonshivering thermogenesis induced in brown adipose tissue (BAT) during high-fat feeding is mediated through uncoupling protein 1 (UCP1). UCP2 is a recently identified homologue found in many tissues. To determine the role of UCP1 and UCP2 in thermoregulation and energy balance, we investigated the long-term effect of high-fat feeding on mRNA levels in mice at two different ambient temperatures. We also treated mice with the anorectic peptide enterostatin and compared mRNA levels in BAT, white adipose tissue (WAT), stomach, and duodenum. Here, we report that high-fat feeding at 23 degrees C increased UCP1 and UCP2 levels in BAT four- and threefold, respectively, and increased UCP2 levels fourfold in WAT. However, at 29 degrees C, UCP1 decreased, whereas UCP2 remained unchanged in BAT and increased twofold in WAT. Enterostatin increased UCP1 and decreased UCP2 mRNA in BAT. In stomach and duodenum, high-fat feeding decreased UCP2 mRNA, whereas enterostatin increased it. Our results suggest that the regulation of uncoupling protein mRNA levels by high-fat feeding is dependent on ambient temperature and that enterostatin is able to modulate it.

  14. Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice.

    PubMed

    Mielke, John G; Nicolitch, Katarina; Avellaneda, Vanessa; Earlam, Karen; Ahuja, Tarun; Mealing, Geoffrey; Messier, Claude

    2006-12-15

    Although the increasing rate of obesity has stimulated interest in the effects of diet composition on peripheral systems, comparatively little work has been done to examine effects upon the brain. A diet high in fat is one of many factors that can promote obesity, and previous research has shown that such a diet can produce learning and memory impairment in rodents. In the present study, C57BL/6 mice were placed on either a high-fat (45% kcal fat) or regular (5% kcal fat) diet, and examined at different points during the subsequent year. The high-fat diet led to increased weight gain, significant impairment in glucoregulation, and altered insulin-mediated signaling within the hippocampus, an area of the brain believed to be important for the acquisition of memory. Following ten months on either diet, synaptic function in ex vivo hippocampal slices was examined, and neither stimulus-response curves nor electrically induced long-term potentiation were found to be different. As well, performance in the Morris water maze, a hippocampal-dependent test of spatial memory, was not influenced by diet. However, mice consuming a high-fat diet failed to perform an operant bar-pressing task, indicating a significant impairment to procedural learning and consolidation processes. Despite causing broad peripheral changes in C57BL/6 mice, consuming a large proportion of calories from saturated fat had only a limited effect upon learning and memory, which suggests that certain aspects of brain function are selectively vulnerable to the influences of diet.

  15. Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

    PubMed

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

    2012-09-28

    We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

  16. Purple Sweet Potato Attenuate Weight Gain in High Fat Diet Induced Obese Mice.

    PubMed

    Ju, Ronghui; Zheng, Shujuan; Luo, Hongxia; Wang, Changgang; Duan, Lili; Sheng, Yao; Zhao, Changhui; Xu, Wentao; Huang, Kunlun

    2017-03-01

    Purple sweet potato (PSP) is widely grown in Asia and considered as a healthy vegetable. The objective of the current study was to determine the anti-obesity effect of the PSP on high fat diet induced obese C57BL/6J mice. The mice were administrated with high fat diet supplemented with the sweet potato (SP) or PSP at the concentration of 15% and 30% for 12 wk, respectively. The results showed that the supplementation of SP or PSP at 30% significantly ameliorated high fat diet induced obesity and its associated risk factors, including reduction of body weight and fat accumulation, improvement of lipid profile and modulation of energy expenditure. Moreover, PSP also posed beneficial effect on the liver and kidney functions. These results indicate that PSP and SP have anti-obesity effect and are effective to reduce the metabolic risk.

  17. Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

    PubMed

    Joslin, P M N; Bell, R K; Swoap, S J

    2016-06-08

    Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (Tb ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and Tb . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse.

  18. Comparison of the behavioral effects of exercise and high fat diet on cognitive function in adolescent rats

    PubMed Central

    Lee, Jae-Min; Park, Jong-Min; Song, Min Kyung; Kim, Yoon Ju; Kim, Youn-Jung

    2016-01-01

    Adolescence is a critical period for neurodevelopment, neuronal plasticity, and cognitive function. Experiences of adolescence can be exerted positive and negative effects on brain development. Physical exercise has a positive effect on brain function, which is characterized by improving memory function and increased neural plasticity. High fat diet (HFD)-induced obesity has a negative effect on brain function, which is characterized by insulin resistance and neuroinflammation and reduced microvessel constructure. Although the positive effect of exercise and negative effect of obesity on cognitive function have been documented, it has not been well whether comparison of the effects of exercise and obesity on cognitive function in adolescent rats. In the present study, we evaluated the behavioral changes related to cognitive function induced by exercise and obesity in adolescent rats. Male Wistar rats were randomly divided into three groups: the control group (CON), the exercise group (Ex), the high fat diet group (HFD). The HFD containing fat 60% was freely provided. The present results showed that spatial learning ability and short-term memory did not show significant effect exercise as compared to the control group. The present results showed that spatial learning ability and short-term memory was significantly decreased HFD-induced obesity group as compared to the control group. These results suggest that positive effect of physical exercise in adolescence rats may be exerted no significant effect on cognitive function. But, negative effect of HFD-induced obesity might induce cognitive impairment. HFD-induced obesity in adolescent rats may be used as an animal model of neurodevelopmental disorders. PMID:28119872

  19. Evolution of metabolic disorder in rats fed high sucrose or high fat diet: Focus on redox state and mitochondrial function.

    PubMed

    Long, Zi; Zhang, Xuesi; Sun, Quangui; Liu, Ying; Liao, Nai; Wu, Hao; Wang, Xin; Hai, Chunxu

    2017-02-01

    Glucotoxicity and lipotoxicity are major hallmarks of metabolic disorder. High consumption of fat or carbohydrate rich food is a major risk of metabolic disorder. However, the evolution of high fat or high carbohydrate diet-induced metabolic disorder is not clear. In the study, we tried to find distinguished and common ways involved in the pathogenesis of insulin resistance induced by high fat (HF) and high sucrose (HS) diet. We found that HS diet induced mild glucose intolerance (2month), followed by a "temporary non-symptom phase" (3month), and then induced significant metabolic abnormality (4month). HF diet induced an early "responsive enhancement phase" (2month), and then gradually caused severe metabolic dysfunction (3-4month). After a mild induction of mitochondrial ROS generation (2month), HS diet resulted in a "temporary non-symptom phase" (3month), and then induced a more significant mitochondrial ROS production (4month). The impairment of mitochondrial function induced by HS diet was progressive (2-4month). HF diet induced gradual mitochondrial ROS generation and hyperpolarization. HF diet induced an early "responsive enhancement" of mitochondrial function (2month), and then gradually resulted in severe decrease of mitochondrial function (3-4month). Despite the patterns of HS and HF diet-induced insulin resistance were differential, final mitochondrial ROS generation combined with mitochondrial dysfunction may be the common pathway. These findings demonstrate a novel understanding of the mechanism of insulin resistance and highlight the pivotal role of mitochondrial ROS generation and mitochondrial dysfunction in the pathogenesis of metabolic disorder.

  20. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

    PubMed

    Sartori, Claudio; Dessen, Pierre; Mathieu, Caroline; Monney, Anita; Bloch, Jonathan; Nicod, Pascal; Scherrer, Urs; Duplain, Hervé

    2009-12-01

    Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.

  1. High-Fat Diet Increased Renal and Hepatic Oxidative Stress Induced by Vanadium of Wistar Rat.

    PubMed

    Wang, J P; Cui, R Y; Zhang, K Y; Ding, X M; Luo, Y H; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

    2016-04-01

    The study was conducted to assess the effect of vanadium (V) in high-fat diet on the liver and kidney of rats in a 5-week trial. Seventy-two female Wistar rats (BW = 95 ± 5 g) were randomly allotted into eight groups. Groups I, II, III, and IV obtained low-fat diet containing 0, 3, 15, and 30 mg/kg V, and V, VI, VII, and VIII groups received the respective vanadium doses with high-fat diet, respectively. There were lesions in the liver and kidney of V, VI, VII, and VIII groups, granular degeneration and vacuolar degeneration were observed in the renal tubular and glomerulus epithelial cells, and hepatocytes showed granular degeneration and vacuolar degeneration. Supplemented high-fat diet with vanadium was shown to decrease (P < 0.05) activities of superoxide dismutase, total antioxidant capacity, glutathione-S transferase, and NAD(P)H/quinone oxidoreductase 1 (NQO1) and increase malondialdehyde content in the liver and kidney. The relative expression of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and NQO1 mRNA was downregulated by V addition and high-fat diet, and the effect of V was more pronounced in high-fat diet (interaction, P < 0.05), with VIII group having the lowest mRNA expression of Nrf-2 and NQO1 in the liver and kidney. In conclusion, it suggested that dietary vanadium ranging from 15 to 30 mg/kg could lead to oxidative damage and vanadium accumulation in the liver and kidney, which caused renal and hepatic toxicity. The high-fat diet enhanced vanadium-induced hepatic and renal damage, and the mechanism was related to the modulation of the hepatic and renal mRNA expression of Nrf-2 and NQO1.

  2. Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast123

    PubMed Central

    Basu, Arpita; Betts, Nancy M; Leyva, Misti J; Fu, Dongxu; Aston, Christopher E; Lyons, Timothy J

    2015-01-01

    Background: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function. Objective: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food–style meal. Methods: Adults with T2D [n = 18; age (mean ± SE): 56 ± 3 y; BMI (in kg/m2): 35.3 ± 2.0; 14 women; 4 men] were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; <0.1 mg flavanols) with a high-fat fast-food–style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10–12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment. Results: Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall Δ: 1.5 ± 0.8 mg/dL; P ≤ 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (Δ: 5.2 ± 3.2 mU/L; P < 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P < 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (Δ: −1.6 ± 0.7 mL/mm Hg; P < 0.05), with the difference significant only at 2 h. Conclusion: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food–style meal challenge

  3. Cardiovascular function in male and female JCR:LA-cp rats: Effect of high fat/high sucrose diet.

    PubMed

    Hunter, Ian; Soler, Amanda; Joseph, Gregory; Hutcheson, Brenda; Bradford, Chastity; Zhang, Frank; Potter, Barry J; Proctor, Spencer D; Rocic, Petra

    2017-01-13

    30% of the world population is diagnosed with metabolic syndrome. High fat/high sucrose diet (HF/HS, Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, coronary collateral development) and cardiac (echocardiography) function, oxidative stress and inflammation in a rat model of metabolic syndrome (JCR). Furthermore, we determined whether male vs. female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired vs. normal rats (SD). HF/HS diet compromised cardiovascular (dys)function in JCR but not in SD male rats. In contrast, cardiovascular function was minimally impaired in JCR females on normal chow. However, cardiovascular function in JCR females on the HF/HS diet deteriorated to levels comparable to JCR males on the HF/HS diet. Similarly, oxidative stress was markedly increased in male but not female JCR rats on normal chow, but was equally exacerbated by the HF/HS diet in male and female JCR rats. These results indicate that the Western diet enhances oxidative stress and cardiovascular dysfunction in metabolic syndrome and eliminates the protective effect of female sex on cardiovascular function, implying that both males and females with metabolic syndrome are at equal risk for cardiovascular disease.

  4. Age and High-Fat Diet Effects on Glutamine Synthetase Immunoreactivity in Liver and Hippocampus and Recognition Memory in Mice

    PubMed Central

    Soontornniyomkij, Virawudh; Kesby, James P.; Soontornniyomkij, Benchawanna; Kim, Jane J.; Kisseleva, Tatiana; Achim, Cristian L.; Semenova, Svetlana; Jeste, Dilip V.

    2016-01-01

    BACKGROUND High-fat diet (HFD)-induced obesity may promote age-related memory impairment via disturbances of ammonia-glutamine metabolism. OBJECTIVE We studied the effects of age and long-term HFD exposure on glutamine synthetase (GS) expression in the liver and hippocampus and recognition memory in mice. METHODS Adult (5-month-old) and aged (15-month-old) male C57BL/6 mice were exposed to control diet (CD, 14% calories from fat) or HFD (60% fat). Novel place recognition testing was conducted and tissue was collected after 4 and 5 months on HFD, respectively. Tissue GS expression levels were assessed using immunohistochemistry and image analysis. RESULTS The obese mice developed moderate/severe hepatic steatosis. GS immunoreactivity was observed in perivenous hepatocytes and in hippocampal astrocytes and neuropil. Hepatic GS immunoreactivity density was higher in aged mice on HFD (n = 8) than CD (n = 13, P = 0.004). In aged mice, hippocampal GS immunoreactivity density was higher with HFD than CD (P = 0.037). In the novel place recognition test, aged mice were classified into impaired (n = 7) and unimpaired (n = 12), relative to adult mice (n = 22). Hippocampal GS immunoreactivity density was higher in impaired than unimpaired aged mice (P < 0.05). CONCLUSION Long-term exposure of aged mice to HFD was associated with increased GS expression in the liver and hippocampus. Novel place recognition impairment in aged mice was associated with increased hippocampal GS expression. These findings suggest that excess ammonia is involved in the age-related effects of HFD exposure and in neurotoxicity. PMID:27071478

  5. Practices and preferences: Exploring the relationships between food-related parenting practices and child food preferences for high fat and/or sugar foods, fruits, and vegetables.

    PubMed

    Vollmer, Rachel L; Baietto, Jamey

    2017-02-21

    The purpose of this study was to determine the relationship between food-related parenting practices and child fruit, vegetable, and high fat/sugar food preferences. Parents (n = 148) of children (3-7 years old) completed the Comprehensive Feeding Practices Questionnaire (CFPQ), the Preschool Adapted Food Liking Scale (PALS), and answered demographic questions. Separate linear regressions were conducted to test relationships between the different food categories on PALS (fruits, vegetables, and high fat/sugar foods) and each food-related parenting practice using race, ethnicity, and income level, and child age and gender as covariates. It was found that when a parent allows a child to control eating, it was negatively associated with a child's preference for fruit (β = -0.15, p = 0.032) and parent encouragement of child involvement in meal preparation was positively related to child preference for vegetables (β = 0.14, p = 0.048). Children preferred high fat and sugar foods more if parents used food to regulate child emotions (β = 0.24, p = 0.007), used food as a reward (β = 0.32, p < 0.001), pressured the child to eat more food (β = 0.16, p = 0.045), and restricted unhealthy food (β = 0.20, p = 0.024). Conversely, children preferred high fat and sugar foods less if parents made healthy food available in the home (β = -0.13, p = 0.05), modeled healthy eating in front of the child (β = -0.21, p = 0.021), and if parents explained why healthy foods should be consumed (β = -0.24, p = 0.011). Although it cannot be determined if the parent is influencing the child or vice versa, this study provides some evidence that coercive feeding practices are detrimental to a child's food preferences.

  6. High fat diet feeding results in gender specific steatohepatitis and inflammasome activation

    PubMed Central

    Ganz, Michal; Csak, Timea; Szabo, Gyongyi

    2014-01-01

    AIM: To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. METHODS: In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. RESULTS: There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no

  7. High-fat diet induces leptin resistance in leptin-deficient mice.

    PubMed

    Koch, C E; Lowe, C; Pretz, D; Steger, J; Williams, L M; Tups, A

    2014-02-01

    The occurrence of type II diabetes is highly correlated with obesity, although the mechanisms linking the two conditions are incompletely understood. Leptin is a potent insulin sensitiser and, in leptin-deficient, insulin insensitive, Lep(ob/ob) mice, leptin improves glucose tolerance, indicating that leptin resistance may link obesity to insulin insensitivity. Leptin resistance occurs in response to a high-fat diet (HFD) and both hyperleptinaemia and inflammation have been proposed as causative mechanisms. Scrutinising the role of hyperleptinaemia in this process, central hyperleptinaemia in Lep(ob/ob) mice was induced by chronic i.c.v. infusion of leptin (4.2 μg/day) over 10 days. This treatment led to a dramatic decline in body weight and food intake, as well as an improvement in glucose tolerance. Transfer to HFD for 4 days markedly arrested the beneficial effects of leptin on these parameters. Because Lep(ob/ob) mice are exquisitely sensitive to leptin, the possibility that leptin could reverse HFD-induced glucose intolerance in these animals was investigated. HFD led to increased body weight and glucose intolerance compared to a low-fat diet (LFD). Older and heavier Lep(ob/ob) mice were used as body weight-matched controls. Mice in each group received either i.p. leptin (1.25 mg/kg) or vehicle, and glucose tolerance, food intake and the number of phosphorylated signal transducer and activator of transcription (pSTAT)3 immunoreactive cells in the arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) were analysed. Leptin improved glucose tolerance (P = 0. 019) and reduced food intake in Lep(ob/ob) mice on LFD (P ≤ 0.001) but was ineffective in mice on HFD. Furthermore, when leptin was administered centrally, the glucose tolerance of Lep(ob/ob) mice on HFD was significantly impaired (P = 0.007). Although leptin induced the number of pSTAT3 immunoreactive cells in the ARC and VMH of Lep(ob/ob) mice on LFD, HFD was associated with elevated pSTAT3

  8. Meals for the Elderly

    NASA Technical Reports Server (NTRS)

    1977-01-01

    NASA is drawing upon its food-preparation expertise to assist in solving a problem affecting a large segment of the American population. In preparation for manned space flight programs, NASA became experienced in providing astronauts simple, easily-prepared, nutritious meals. That experience now is being transferred to the public sector in a cooperative project managed by Johnson Space Center. Called Meal System for the Elderly, the project seeks to fill a gap by supplying nutritionally balanced meal packages to those who are unable to participate in existing meal programs. Many such programs are conducted by federal, state and private organizations, including congregate hot meal services and home-delivered "meals on wheels." But more than 3.5 million elderly Americans are unable to take advantage of these benefits. In some cases, they live in rural areas away from available services; in others, they are handicapped, temporarily ill, or homebound for other reasons. Meal System for the Elderly, a cooperative program in which the food-preparation expertise NASA acquired in manned space projects is being utilized to improve the nutritional status of elderly people. The program seeks to fill a gap by supplying nutritionally-balanced food packages to the elderly who are unable to participate b existing meal service programs.

  9. The Timing of Meals

    ERIC Educational Resources Information Center

    Strubbe, Jan H.; Woods, Stephen C.

    2004-01-01

    In most individuals, food intake occurs as discrete bouts or meals, and little attention has been paid to the factors that normally determine when meals will occur when food is freely available. On the basis of experiments using rats, the authors suggest that when there are no constraints on obtaining food and few competing activities, 3 levels of…

  10. Meals for the Elderly

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The aim of Skylab's multi-agency cooperative project was to make simple but nutritious space meals available to handicapped and otherwise homebound senior adults, unable to take advantage of existing meal programs sponsored by federal, state and private organizations. As a spinoff of Meal Systems for the Elderly, commercial food processing firms are now producing astronaut type meals for public distribution. Company offers variety of freeze dried foods which are reconstituted by addition of water, and "retort pouch" meals which need no reconstitution, only heating. The retort pouch is an innovative flexible package that combines the advantage of boil-in bag and metal can. Foods retain their flavor, minerals and vitamins can be stored without refrigeration and are lightweight for easy transportation.

  11. Deletion of CDKAL1 Affects High-Fat Diet–Induced Fat Accumulation and Glucose-Stimulated Insulin Secretion in Mice, Indicating Relevance to Diabetes

    PubMed Central

    Takeuchi, Fumihiko; Isono, Masato; Akiyama, Koichi; Shimizu, Yukiko; Goto, Motohito; Liang, Yi-Qiang; Yamamoto, Ken; Katsuya, Tomohiro; Fujioka, Akihiro; Ohnaka, Keizo; Takayanagi, Ryoichi; Ogihara, Toshio; Yamori, Yukio; Kato, Norihiro

    2012-01-01

    Background/Objective The CDKAL1 gene is among the best-replicated susceptibility loci for type 2 diabetes, originally identified by genome-wide association studies in humans. To clarify a physiological importance of CDKAL1, we examined effects of a global Cdkal1-null mutation in mice and also evaluated the influence of a CDKAL1 risk allele on body mass index (BMI) in Japanese subjects. Methods In Cdkal1-deficient (Cdkal1−/−) mice, we performed oral glucose tolerance test, insulin tolerance test, and perfusion experiments with and without high-fat feeding. Based on the findings in mice, we tested genetic association of CDKAL1 variants with BMI, as a measure of adiposity, and type 2 diabetes in Japanese. Principal Findings On a standard diet, Cdkal1−/− mice were modestly lighter in weight than wild-type littermates without major alterations in glucose metabolism. On a high fat diet, Cdkal1−/− mice showed significant reduction in fat accumulation (17% reduction in %intraabdominal fat, P = 0.023 vs. wild-type littermates) with less impaired insulin sensitivity at an early stage. High fat feeding did not potentiate insulin secretion in Cdkal1−/− mice (1.0-fold), contrary to the results in wild-type littermates (1.6-fold, P<0.01). Inversely, at a later stage, Cdkal1−/− mice showed more prominent impairment of insulin sensitivity and glucose tolerance. mRNA expression analysis indicated that Scd1 might function as a critical mediator of the altered metabolism in Cdkal1−/− mice. In accordance with the findings in mice, a nominally significant (P<0.05) association between CDKAL1 rs4712523 and BMI was replicated in 2 Japanese general populations comprising 5,695 and 12,569 samples; the risk allele for type 2 diabetes was also associated with decreased BMI. Conclusions Cdkal1 gene deletion is accompanied by modestly impaired insulin secretion and longitudinal fluctuations in insulin sensitivity during high-fat feeding in mice. CDKAL1 may affect

  12. Blueberry supplementation improves memory in middle-aged mice consuming a high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consuming a high fat (HF) diet may result in behavioral deficits similar to those observed in aging animals, possibly because of increased brain inflammation and oxidative stress. Our lab has demonstrated that diets supplemented with polyphenolic-rich berries, such as blueberries (BB), can allay beh...

  13. Methyl Donor Supplementation Blocks the Adverse Effects of Maternal High Fat Diet on Offspring Physiology

    PubMed Central

    Reyes, Teresa M.

    2013-01-01

    Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60%) diet leads to global and gene specific decreases in DNA methylation in the brain of the offspring. The present experiments were designed to attempt to reverse this DNA hypomethylation through supplementation of the maternal diet with methyl donors, and to determine whether methyl donor supplementation could block or attenuate phenotypes associated with maternal consumption of a HF diet. Metabolic and behavioral (fat preference) outcomes were assessed in male and female adult offspring. Expression of the mu-opioid receptor and dopamine transporter mRNA, as well as global DNA methylation were measured in the brain. Supplementation of the maternal diet with methyl donors attenuated the development of some of the adverse effects seen in offspring from dams fed a high fat diet; including weight gain, increased fat preference (males), changes in CNS gene expression and global hypomethylation in the prefrontal cortex. Notable sex differences were observed. These findings identify the importance of balanced methylation status during pregnancy, particularly in the context of a maternal high fat diet, for optimal offspring outcome. PMID:23658839

  14. Disruption of Daily Rhythms by High-Fat Diet Is Reversible

    PubMed Central

    Branecky, Katrina L.; Niswender, Kevin D.; Pendergast, Julie S.

    2015-01-01

    In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low-fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered for the duration of chronic high-fat diet feeding. Upon diet reversal, the eating behavior rhythm was rapidly reversed (within 2 days) and the phase of the liver clock was restored by 7 days of diet reversal. In contrast, the daily pattern of locomotor activity was not restored even after 2 weeks of diet reversal. Thus, while the circadian system is sensitive to changes in the macronutrient composition of food, the eating behavior rhythm and liver circadian clock are specifically tuned to respond to changes in diet. PMID:26366733

  15. A Krill Oil Supplemented Diet Suppresses Hepatic Steatosis in High-Fat Fed Rats

    PubMed Central

    Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

    2012-01-01

    Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals. PMID:22685607

  16. Effects of high fat diet and prednisolone treatment on femoral head separation in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of high fat diets or transient treatment with cholesterol or a synthetic glucocorticoid, prednisolone, on femoral head fragility of broiler chickens was examined along with other production parameters such as growth, feed conversion, and blood chemistry. Three groups of broiler chicks co...

  17. Effects of high fat diet and prednisolone on femoral head separation in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of high fat diets or transient treatment with cholesterol or a synthetic glucocorticoid, prednisolone, on femoral head fragility of broiler chickens was examined along with other production parameters such as growth, feed conversion, and blood chemistry. Three groups of broiler chicks co...

  18. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypoth...

  19. A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

    PubMed

    Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

    2012-01-01

    Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

  20. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  1. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  2. Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine initiated early hepatocarcinogenesis in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) are at a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen die...

  3. Is Childhood Obesity Associated with High-Fat Foods and Low Physical Activity?

    ERIC Educational Resources Information Center

    Muecke, Lee; And Others

    1992-01-01

    Study investigated whether high-fat food consumption and low physical activity were risk factors for obesity in third graders. Tests revealed a greater prevalence of childhood obesity in 1985 than in 1976-80. Neither intake nor activity level were independent risk factors, but there may be synergistic effects with both present. (SM)

  4. Effects of high-fat diets composed of different oils on adipokine production in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated (n3) fatty acids in fish oil are shown to exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines. In this study, we compared high-fat diets composed of different dietary oils with various le...

  5. Nonalcoholic Steatohepatitis Induced by a High-Fat Diet Promotes Diethylnitrosamine Initiated Early Hepatocarcinogenesis in Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) have a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes chemical carcinogen-initiated hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low d...

  6. Eicosapentaenoic acid regulates brown adipose tissue gene expression and metabolism in high fat fed mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) is a thermogenic tissue, a key regulator of energy balance and a potential therapeutic target for obesity. We previously reported that eicosapentaenoic acid (EPA) reduced high fat (HF) diet-induced obesity and insulin resistance in mice, independent of energy intake. We hy...

  7. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

    PubMed

    Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

    2017-03-01

    Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

  8. Influence of dietary fatty acid composition and exercise on changes in fat oxidation from a high-fat diet.

    PubMed

    Cooper, J A; Watras, A C; Shriver, T; Adams, A K; Schoeller, D A

    2010-10-01

    Acute high-fat (HF) diets can lead to short-term positive fat balances until the body increases fat oxidation to match intake. The purpose of this study was to examine the effects of a HF diet, rich in either mono-unsaturated or saturated fatty acids (FAs) and exercise, on the rate at which the body adapts to a HF diet.(13)C-labeled oleate and (2)H-labeled palmitate were also given to determine the contribution of exogenous vs. global fat oxidation. Eight healthy men (age of 18-45 yr; body mass index of 22 ± 3 kg/m(2)) were randomized in a 2 × 2 crossover design. The four treatments were a high saturated fat diet with exercise (SE) or sedentary (SS) conditions and a high monounsaturated fat diet with exercise (UE) or sedentary (US) conditions. Subjects stayed for 5 days in a metabolic chamber. All meals were provided. On day 1, 30% of energy intake was from fat, whereas days 2-5 had 50% of energy as fat. Subjects exercised on a stationary cycle at 45% of maximal oxygen uptake for 2 h each day. Respiratory gases and urinary nitrogen were collected to calculate fat oxidation. Change from day 1 to day 5 showed both exercise treatments increased fat oxidation (SE: 76 ± 30 g, P = 0.001; UE: 118 ± 31 g, P < 0.001), whereas neither sedentary condition changed fat oxidation (SS: -10 ± 33 g, P = not significant; US: 41 ± 14 g, P = 0.07). No differences for dietary FA composition were found. Exercise led to a faster adaptation to a HF diet by increasing fat oxidation and achieving fat balance by day 5. Dietary FA composition did not differentially affect 24-h fat oxidation.

  9. Improvement of Cardiomyopathy After High-Fat Diet in Two Siblings with Glycogen Storage Disease Type III.

    PubMed

    Brambilla, Alessandra; Mannarino, Savina; Pretese, Roberta; Gasperini, Serena; Galimberti, Cinzia; Parini, Rossella

    2014-01-01

    Glycogenosis type III (GSD III) is an autosomal recessive disorder due to amylo-1,6-glucosidase deficiency. This disease causes limit dextrin storage in affected tissues: liver, skeletal muscles, and heart in GSD IIIa and only liver in GSD IIIb. Cardiomyopathy is quite frequent in GSD IIIa with variable severity and progression of manifestations. It is not clear if diet manipulation may interfere with cardiomyopathy's progression. Recent case reports showed improvement of cardiomyopathy following a ketogenic diet.Two siblings (girl and boy), 7- and 5-year-old, both affected with GSD IIIa, developed severe and rapidly worsening left ventricular hypertrophy in the first years of life, while treated with frequent diurnal and nocturnal hyperproteic meals followed by orally administered uncooked cornstarch. Subsequently they were treated with high-fat (60%) and high-protein (25%), low-carbohydrate (15%) diet. After 12 months exertion dyspnea disappeared in the girl and biochemical blood tests, cardiac enzymes, and congestive heart failure markers improved in both (CK 3439→324, 1304→581 U/L; NT-proBNP 2084→206, 782→135 pg/mL, respectively); ultrasound assessment in both patients showed a relevant reduction of the thickness of interventricular septum (30→16, 16→11 mm, respectively) and left ventricle posterior wall (18→7, 13→8 mm, respectively) and an improvement of the outflow obstruction. A diet rich in fats as well as proteins and poor in carbohydrates could be a beneficial therapeutic choice for GSD III with cardiomyopathy. Future research is needed to confirm the beneficial effect of this treatment and to design treatment strategies with the aim to provide alternative source of energy and prevent glycogen accumulation.

  10. Enhanced flavor-nutrient conditioning in obese rats on a high-fat, high-carbohydrate choice diet.

    PubMed

    Wald, Hallie S; Myers, Kevin P

    2015-11-01

    Through flavor-nutrient conditioning rats learn to prefer and increase their intake of flavors paired with rewarding, postingestive nutritional consequences. Since obesity is linked to altered experience of food reward and to perturbations of nutrient sensing, we investigated flavor-nutrient learning in rats made obese using a high fat/high carbohydrate (HFHC) choice model of diet-induced obesity (ad libitum lard and maltodextrin solution plus standard rodent chow). Forty rats were maintained on HFHC to induce substantial weight gain, and 20 were maintained on chow only (CON). Among HFHC rats, individual differences in propensity to weight gain were studied by comparing those with the highest proportional weight gain (obesity prone, OP) to those with the lowest (obesity resistant, OR). Sensitivity to postingestive food reward was tested in a flavor-nutrient conditioning protocol. To measure initial, within-meal stimulation of flavor acceptance by post-oral nutrient sensing, first, in sessions 1-3, baseline licking was measured while rats consumed grape- or cherry-flavored saccharin accompanied by intragastric (IG) water infusion. Then, in the next three test sessions they received the opposite flavor paired with 5 ml of IG 12% glucose. Finally, after additional sessions alternating between the two flavor-infusion contingencies, preference was measured in a two-bottle choice between the flavors without IG infusions. HFHC-OP rats showed stronger initial enhancement of intake in the first glucose infusion sessions than CON or HFHC-OR rats. OP rats also most strongly preferred the glucose-paired flavor in the two-bottle choice. These differences between OP versus OR and CON rats suggest that obesity is linked to responsiveness to postoral nutrient reward, consistent with the view that flavor-nutrient learning perpetuates overeating in obesity.

  11. High-fat feeding induces angiogenesis in skeletal muscle and activates angiogenic pathways in capillaries.

    PubMed

    Silvennoinen, Mika; Rinnankoski-Tuikka, Rita; Vuento, Mikael; Hulmi, Juha J; Torvinen, Sira; Lehti, Maarit; Kivelä, Riikka; Kainulainen, Heikki

    2013-04-01

    High-fat diet (HFD) increases fatty acid oxidation in skeletal muscles. We hypothesized that this leads to increased oxygen demand and thus to increased capillarization. We determined the effects of high-fat diet on capillarization and angiogenic factors in skeletal muscles of mice that were either active or sedentary. Fifty-eight C57BL/6 J mice were divided into four groups: low-fat diet sedentary (LFS), low-fat diet active (LFA), high-fat diet sedentary (HFS), and high-fat diet active (HFA). The mice in active groups were housed in cages with running wheels and the sedentary mice were housed in similar cages without running wheels. After 19 weeks HFS, LFA and HFA had higher capillary density and capillary-to-fiber-ratio in quadriceps femoris muscles than LFS. Capillarization was similar in HFS and HFA. To reveal possible mechanisms of HFD induced angiogenesis, we measured protein and mRNA levels of angiogenic factors VEGF-A, HIF-1α, PGC-1α and ERRα. VEGF-A protein levels were higher in muscles of HFS, LFA and HFA compared to LFS. However, no significant differences were observed between HFA and HFS. Protein levels of HIF-1α, PGC-1α, and ERRα were similar in all groups. However, the mRNA expression of HIF-1α and VEGF-A was up-regulated in capillaries but not in muscle fibers of HFS. The sedentary and active mice groups had similar mRNA expression levels of angiogenesis regulators studied. We conclude that high-fat feeding induces angiogenesis in skeletal muscle and up-regulates the gene expression of HIF-1α and VEGF-A in capillaries.

  12. Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients.

    PubMed

    Zhang, Lianshan; Liang, Libin; Tong, Tong; Qin, Yuguo; Xu, Yanping; Tong, Xinglong

    2016-10-01

    Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice. Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients. Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet + ATP group. ATP supplementation (40 mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60 mg twice a day for 1 week. Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p < 0.01). ATP treatment significantly decreased serum TG level (p < 0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p < 0.05) and pathological gradation of ballooning degeneration in hepatocytes (p < 0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p < 0.01), but other lipid parameters had no significant change. Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.

  13. High-fat, cholesterol-rich diet affects leptin expression in the aortic layers.

    PubMed

    Krawczynska, Agata; Olczak, Elzbieta; Rembiszewska, Alina; Gromadzka-Ostrowska, Joanna

    2013-01-01

    Leptin is stated to be an important mediator between obesity and cardiovascular disease. However, whether leptin location in the aorta is dependent on diet and its atherogenic character is still unknown. This study examined the relationship between a high-fat diet with or without cholesterol and the expression of leptin in aortic layers. Forty male rats were fed a high-fat diet with fish or grape seed oil as a dietary fat source, with or without cholesterol, to enhance the atherogenic character of their diet. The experiments lasted for three and six weeks, respectively. Plasma lipid profile, plasma leptin concentration and leptin expression in the endothelium (E), myometrium (M) and adventitia (A) were examined. The length of feeding was a key factor which influenced both the lipid profile and leptin expression in the aorta. Leptin concentration positively correlated with body weight and plasma triglycerides only in the three-week experiment, which suggests that the physiological actions of leptin can be disturbed by prolonged consumption of a high-fat diet. Short-term intake of a high-fat diet with fish oil, increasing high density lipoprotein cholesterol (HDL) level and decreasing total cholesterol (TC)/HDL ratio, enhanced leptin expression in E in comparison to the group fed grape seed oil. However, in the group with the highest diet intake, leptin expression in each layer was lowest. Generally, leptin expression was most common in E; however, an extension of the period of feeding in groups fed a diet with grape seed oil with or without additional cholesterol increased leptin presence in M and A in comparison to the group fed fish oil. Significantly higher values of TC and HDL in the same groups may suggest that leptin changes in the aorta and the atherogenic impact of grape seed oil can be connected when the consumption of a high-fat diet is excessive.

  14. Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs.

    PubMed

    Puccinelli, E; Gervasi, P G; Trivella, M G; Vornoli, A; Viglione, F; Pelosi, G; Parodi, O; Sampietro, T; Puntoni, M

    2015-06-01

    A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n=7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n=5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n=7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C.

  15. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats.

    PubMed

    Takahashi, Kei; Fukuwatari, Tsutomu; Shibata, Katsumi

    2015-01-01

    It is thought that both exercise and dietary composition increase the utilization of, and thus the requirement for, certain water-soluble vitamins. However, there have been no studies evaluating the combined impacts of exercise and dietary composition on vitamin utilization. In this experiment, rats were fed a pantothenic acid (PaA)-restricted (0.004 g PaA-Ca/kg diet) diet containing 5% (ordinary amount of dietary fat) or 20% fat (high fat), and were forced to swim until exhaustion every other day for 22 d. PaA status was assessed by urinary excretion, which reflects body stores of water-soluble vitamins. The urinary excretion of PaA in rats fed a 5% fat diet was not affected by swimming (5% fat + non-swimming vs. 5% fat + swim; p>0.05). Excretion of PaA was decreased by the high-fat diet (5% fat + non-swim vs. 20% fat + non-swim; p<0.05) and synergistically decreased by exercise (20% fat + non-swim vs. 20% fat + swim; p<0.05). There was a significant interaction between exercise and a high-fat diet. Plasma PaA concentrations showed changes similar to those seen for urinary excretion. The experiment was then repeated using rats fed a PaA-sufficient (0.016 g PaA-Ca/kg diet) diet, and PaA excretion was again synergistically decreased by the combination of exercise and a high-fat diet (p<0.05). These results suggest that the combination of exercise and a high-fat diet synergistically increases the requirement for PaA.

  16. Public support for policy initiatives regulating high-fat food use in Minnesota: a multicommunity survey.

    PubMed

    Schmid, T L; Jeffery, R W; Forster, J L; Rooney, B; McBride, C

    1989-11-01

    Public support of eight policies to regulate the sale and consumption of high-fat food was evaluated in a survey of 438 women and 383 men in seven Minnesota communities. The survey was part of the ongoing activities of the Minnesota Heart Health Program (MHHP). Respondents, when asked to indicate their level of support or opposition to each of eight policies, expressed general support for all but two. Women were consistently more supportive than men. Other sociodemographic characteristics and reported use of food and other substances were generally not predictive of support. Policies that would control conditions of sale or information about the product were the most strongly supported. Taxation as an incentive to food producers to provide alternatives to high-fat food or as a disincentive to consumers to purchase these foods was moderately supported. A proposal to limit sale of high-fat food to children was the most strongly opposed. The majority of respondents indicated that they felt the individual consumer, as opposed to the producer or retailer, is most responsible for problems associated with high-fat food use. The three communities which had received MHHP health promotion activities were significantly more supportive than the comparison communities on two of the eight proposals. There is a moderate level of support in the general public for additional policies to regulate the sale and consumption of high-fat foods. These policy level interventions, similar to policies common in the regulation of alcohol and tobacco use, may be a feasible strategy to help moderate use of potentially health-compromising food products.

  17. Antioxidant effects of fucoxanthin rich powder in rats fed with high fat diet

    PubMed Central

    Ha, Ae Wha; Na, Se Jung

    2013-01-01

    The purpose of this study was to determine the antioxidant effect of fucoxanthin. After rats were fed a normal fat diet (NF), high fat diet (HF), and high fat with 0.2% fucoxanthin diet (HF + Fxn) for 4 weeks, the markers of oxidative stress and antioxidant capacity like lipid peroxidation, plasma total antioxidant capacity (TAC), and activities of antioxidant enzymes (catalase, superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px)) were determined. mRNA expression of transcription factor, nuclear erythroid factor like 2 (Nrf2), and its target genes such as NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase-1 (HO-1) were also determined. Mean weight gain in the HF + Fxn group was lower, without statistical significance, and the total food intake in the HF + Fxn group was lower than that in the HF group (P < 0.05). The activity of GSH-Px (P < 0.05) in plasma was significantly higher in the HF + Fxn group than those in the HF group (P < 0.05). In the liver, the activities of catalase (P < 0.05) and GSH-Px (P < 0.05) in the HF + Fxn group were significantly higher than those in the HF group. Plasma TAC level was significantly higher in the HF + Fxn group than that in the HF group (P < 0.05). Lipid peroxidation in plasma tended to be lower without statistical significance. Fucoxanthin supplements were shown to have higher mRNA expression of Nrf2 and NQO1 than those in the high fat diet only group (P < 0.05). In conclusion, supplementation of fucoxanthin improved the antioxidant capacity, depleted by high fat diet, by activating the Nrf2 pathway and its downstream target gene NQO1. Therefore, supplementation of fucoxanthin, especially for those who consume high fat in their diet, may benefit from reduced risk of oxidative stress. PMID:24353833

  18. Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

    SciTech Connect

    Lu, Yunxia; Cheng, Jingjing; Chen, Li; Li, Chaofei; Chen, Guanjun; Gui, Li; Shen, Bing; Zhang, Qiu

    2015-02-27

    Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric

  19. Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats.

    PubMed

    Nakajima, Shingo; Hira, Tohru; Hara, Hiroshi

    2015-05-14

    Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity.

  20. Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

    PubMed Central

    Sundaram, Sneha; Yan, Lin

    2016-01-01

    The objective of this study was to determine whether a reduction in energy intake ameliorated the high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma in mice. Male C57BL/6 mice were fed the AIN93G diet, a high-fat diet or a high-fat diet with a 5% restriction of the intake. Energy restriction reduced body adiposity and body weight, but maintained growth similar to mice fed the AIN93G diet. The high-fat diet significantly increased the number and size (cross-sectional area and volume) of metastases formed in lungs. Restricted feeding reduced the number of metastases by 23%, metastatic cross-sectional area by 32% and volume by 45% compared to the high-fat diet. The high-fat diet elevated plasma concentrations of proinflammatory cytokines (monocyte chemotactic protein-1, plasminogen activator inhibitor-1, leptin), angiogenic factors (vascular endothelial growth factor, tissue inhibitor of metalloproteinase-1) and insulin. Restricted feeding significantly reduced the high-fat diet-induced elevations in plasma concentrations of proinflammatory cytokines, angiogenic factors and insulin. These results demonstrated that a reduction in diet intake by 5% reduced high-fat diet-enhanced metastasis, which may be associated with the mitigation of adiposity and down-regulation of cancer-promoting proinflammatory cytokines and angiogenic factors. PMID:27582541

  1. Dietary energy restriction reduces high-fat diet-enhanced metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cancer. The objective of this study was to determine the effects of dietary energy restriction on high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC) in mice. Male C57BL/6 mice were fed an AIN93G diet or a high-fat diet (16% or 45% of energy fro...

  2. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

  3. Effects of Meals High in Carbohydrate, Protein, and Fat on Ghrelin and Peptide YY Secretion in Prepubertal Children

    PubMed Central

    Lomenick, Jefferson P.; Melguizo, Maria S.; Mitchell, Sabrina L.; Summar, Marshall L.; Anderson, James W.

    2009-01-01

    Context: Ghrelin and peptide YY (PYY) are two hormones produced by the gastrointestinal tract that have effects on appetite. However, little is known about their secretion in response to meals high in individual macronutrients in prepubertal children. Objective: We sought to understand how meals high in carbohydrate, protein, and fat affect serum concentrations of total ghrelin and total PYY, hypothesizing that these macronutrients would exert differential effects on their secretion. Design and Setting: This was a cross-sectional study at one tertiary care center. Subjects: Subjects were 7- to 11-yr-old healthy normal-weight (NW) and obese (OB) volunteers recruited from local advertisements. Interventions: After an overnight fast, the subjects were given a breakfast high in carbohydrate, protein, or fat at 0800 h. Blood samples for total ghrelin and total PYY were taken at baseline, 30 min, and hourly from 0900 to 1200 h. Main Outcome Measure: We assessed postprandial ghrelin suppression and PYY elevation, as well as changes in reported hunger and satiety, after the three test meals. Results: After the high-protein meal, ghrelin declined gradually in both groups over the study period without subsequent increase, whereas ghrelin suppressed more rapidly to a nadir at 60 min after the high-carbohydrate meal in both NW and OB children, followed by rebound in ghrelin levels. Similarly, after the high-protein meal, PYY concentrations increased steadily over the course of the morning in both groups without decline, whereas PYY levels peaked 30 min after the high-carbohydrate meal in both NW and OB subjects with significant decline thereafter. Ghrelin and PYY responses to the high-fat meal were somewhat intermediate between that observed with high carbohydrate and high protein. The OB children reported higher hunger and lower satiety after the high-carbohydrate meal compared to the NW subjects, whereas appetite ratings were similar between the groups after the high

  4. High-Fat Feeding Does Not Disrupt Daily Rhythms in Female Mice because of Protection by Ovarian Hormones

    PubMed Central

    Palmisano, Brian T.; Stafford, John M.; Pendergast, Julie S.

    2017-01-01

    Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured daily rhythms. Female mice retained robust rhythms of eating behavior and locomotor activity during high-fat feeding that were similar to chow-fed females. In addition, the phase of the liver molecular timekeeping (PER2:LUC) rhythm was not altered by high-fat feeding in females. To determine if ovarian hormones protected daily rhythms in female mice from high-fat feeding, we analyzed rhythms in ovariectomized mice. During high-fat feeding, the amplitudes of the eating behavior and locomotor activity rhythms were reduced in ovariectomized females. Liver PER2:LUC rhythms were also advanced by ~4 h by high-fat feeding, but not chow, in ovariectomized females. Together these data show circulating ovarian hormones protect the integrity of daily rhythms in female mice during high-fat feeding. PMID:28352249

  5. High-Fat Feeding Does Not Disrupt Daily Rhythms in Female Mice because of Protection by Ovarian Hormones.

    PubMed

    Palmisano, Brian T; Stafford, John M; Pendergast, Julie S

    2017-01-01

    Obesity in women is increased by the loss of circulating estrogen after menopause. Shift work, which disrupts circadian rhythms, also increases the risk for obesity. It is not known whether ovarian hormones interact with the circadian system to protect females from obesity. During high-fat feeding, male C57BL/6J mice develop profound obesity and disruption of daily rhythms. Since C57BL/6J female mice did not develop diet-induced obesity (during 8 weeks of high-fat feeding), we first determined if daily rhythms in female mice were resistant to disruption from high-fat diet. We fed female PERIOD2:LUCIFERASE mice 45% high-fat diet for 1 week and measured daily rhythms. Female mice retained robust rhythms of eating behavior and locomotor activity during high-fat feeding that were similar to chow-fed females. In addition, the phase of the liver molecular timekeeping (PER2:LUC) rhythm was not altered by high-fat feeding in females. To determine if ovarian hormones protected daily rhythms in female mice from high-fat feeding, we analyzed rhythms in ovariectomized mice. During high-fat feeding, the amplitudes of the eating behavior and locomotor activity rhythms were reduced in ovariectomized females. Liver PER2:LUC rhythms were also advanced by ~4 h by high-fat feeding, but not chow, in ovariectomized females. Together these data show circulating ovarian hormones protect the integrity of daily rhythms in female mice during high-fat feeding.

  6. Dissociation between PGC-1alpha and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet.

    PubMed

    Higashida, Kazuhiko; Higuchi, Mitsuru; Terada, Shin

    2009-12-01

    It has recently been reported that a 4-wk high-fat diet gradually increases skeletal muscle peroxisome proliferator activated receptor (PPAR) gamma coactivator-1alpha (PGC-1alpha) protein content, which has been suggested to regulate GLUT-4 gene transcription. However, it has not been reported that a high-fat diet enhances GLUT-4 mRNA expression and protein content in skeletal muscle, suggesting that an increase in PGC-1alpha protein content is not sufficient to induce muscle GLUT-4 biogenesis in a high-fat fed animal. Therefore, we first evaluated the relationship between PGC-1alpha and GLUT-4 expression in skeletal muscle of rats fed a high-fat diet for 4 wk. The PGC-1alpha protein content in rat epitrochlearis muscle significantly increased by twofold after the 4-wk high-fat diet feeding. However, the high-fat diet had no effect on GLUT-4 protein content and induced a 30% decrease in GLUT-4 mRNA expression in rat skeletal muscle (p<0.05). To clarify the mechanism by which a high-fat diet downregulates GLUT-4 mRNA expression, we next examined the effect of PPARdelta activation, which is known to occur in response to a high-fat diet, on GLUT-4 mRNA expression in L6 myotubes. Incubation with 500 nM GW501516 (PPARdelta activator) for 24 h significantly decreased GLUT-4 mRNA in L6 myotubes. Taken together, these findings suggest that a high-fat diet downregulates GLUT-4 mRNA, possibly through the activation of PPARdelta, despite an increase in PGC-1alpha protein content in rat skeletal muscle, and that a posttranscriptional regulatory mechanism maintains GLUT-4 protein content in skeletal muscle of rats fed a high-fat diet.

  7. The Effects of Two Lactobacillus plantarum Strains on Rat Lipid Metabolism Receiving a High Fat Diet

    PubMed Central

    Salaj, Rastislav; Štofilová, Jana; Šoltesová, Alena; Hertelyová, Zdenka; Hijová, Emília; Bertková, Izabela; Strojný, Ladislav; Kružliak, Peter

    2013-01-01

    The aim of our study was to evaluate the effects of the different probiotic strains, Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96, on lipid metabolism and body weight in rats fed a high fat diet. Compared with the high fat diet group, the results showed that Lactobacillus plantarum LS/07 reduced serum cholesterol and LDL cholesterol, but Lactobacillus plantarum Biocenol LP96 decreased triglycerides and VLDL, while there was no change in the serum HDL level and liver lipids. Both probiotic strains lowered total bile acids in serum. Our strains have no significant change in body weight, gain weight, and body fat. These findings indicate that the effect of lactobacilli on lipid metabolism may differ among strains and that the Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96 can be used to improve lipid profile and can contribute to a healthier bowel microbial balance. PMID:24470789

  8. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.

    PubMed

    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E

    2011-11-30

    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets.

  9. The effects of two Lactobacillus plantarum strains on rat lipid metabolism receiving a high fat diet.

    PubMed

    Salaj, Rastislav; Stofilová, Jana; Soltesová, Alena; Hertelyová, Zdenka; Hijová, Emília; Bertková, Izabela; Strojný, Ladislav; Kružliak, Peter; Bomba, Alojz

    2013-01-01

    The aim of our study was to evaluate the effects of the different probiotic strains, Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96, on lipid metabolism and body weight in rats fed a high fat diet. Compared with the high fat diet group, the results showed that Lactobacillus plantarum LS/07 reduced serum cholesterol and LDL cholesterol, but Lactobacillus plantarum Biocenol LP96 decreased triglycerides and VLDL, while there was no change in the serum HDL level and liver lipids. Both probiotic strains lowered total bile acids in serum. Our strains have no significant change in body weight, gain weight, and body fat. These findings indicate that the effect of lactobacilli on lipid metabolism may differ among strains and that the Lactobacillus plantarum LS/07 and Lactobacillus plantarum Biocenol LP96 can be used to improve lipid profile and can contribute to a healthier bowel microbial balance.

  10. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

    PubMed

    Kubota, N; Terauchi, Y; Miki, H; Tamemoto, H; Yamauchi, T; Komeda, K; Satoh, S; Nakano, R; Ishii, C; Sugiyama, T; Eto, K; Tsubamoto, Y; Okuno, A; Murakami, K; Sekihara, H; Hasegawa, G; Naito, M; Toyoshima, Y; Tanaka, S; Shiota, K; Kitamura, T; Fujita, T; Ezaki, O; Aizawa, S; Kadowaki, T

    1999-10-01

    Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

  11. Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia

    PubMed Central

    Morimoto, M; Lee, E-Y; Zhang, X; Inaba, Y; Inoue, H; Ogawa, M; Shirasawa, T; Yokosuka, O; Miki, T

    2016-01-01

    Background/Objective: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. Methods: We examined the antidiabetic effect of EPA in insulin receptor mutant (InsrP1195L/+) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. Results: EPA supplementation was found to alleviate hyperglycemia of InsrP1195L/+ mice fed HFD (InsrP1195L/+/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in InsrP1195L/+ mice but not in wild-type mice, suggesting that InsrP1195L/+ mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of InsrP1195L/+ mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. Conclusions: EPA exerts an antidiabetic effect in InsrP1195L/+/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia. PMID:27348201

  12. Inhibitory effects of cardiotonic pills on platelet function in dogs fed a high-fat diet.

    PubMed

    Zhang, Lei; Zheng, Jun; Li, Hui-Min; Meng, Yong-Xia

    2006-06-01

    Insulin resistance and the consequent metabolic disorders are associated with a state of platelet hyperactivity. Oxidative stress is responsible for the persistent platelet activation. We sought to study the inhibitory effect of cardiotonic pills, an oral herbal component, on platelet function in a dog model with insulin resistance induced by high-fat feeding. We fed 18 dogs with a high-fat diet and six dogs with normal chow as control for 6 months. Then, six dogs were fed with a high-fat diet and received additional aspirin (250 mg/day), and another six dogs received additional cardiotonic pills (1,000 mg/day) for 4 months. Time-course changes in metabolic parameters and platelet function were detected. After high-fat feeding for 6 months, 18 dogs developed a series of metabolic disorders including obesity, dyslipidemia, oxidative stress and insulin resistance. In addition, a platelet hyperactivity state, characterized by increased agonist (arachidonic acid, ADP and collagen) induced platelet aggregation, platelet expression of adhesion molecules (P-selectin and GP IIb/IIIa), and platelet intracellular calcium concentration, was indicated. Cardiotonic pills showed a significant antioxidative activity by presenting an increase in plasma superoxide dismutase and decrease in erythrocyte glutathione, as well as a lipid-lowering effect (decrease in both plasma cholesterol and triglyceride). Either aspirin or cardiotonic pills could significantly reverse the platelet hypersensitivity and hyperfunction. Compared with aspirin, cardiotonic pills showed a more exaggerated inhibitory effect on platelet function (a significantly decreased collagen-stimulated platelet aggregation, and expression of adhesion molecules). In conclusion, cardiotonic pills inhibited platelet hyperfunction in dogs with insulin resistance. This inhibitory effect may mainly be explained by antioxidative activity and metabolic control.

  13. Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice

    PubMed Central

    Morton, Tiffany L.; Galior, Kornelia; McGrath, Cody; Wu, Xin; Uzer, Gunes; Uzer, Guniz Bas; Sen, Buer; Xie, Zhihui; Tyson, David; Rubin, Janet; Styner, Maya

    2016-01-01

    Muscle lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete’s paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high-fat diet (HFD for 6 or 18 weeks) were further divided into sedentary or exercising groups (CTL-E or HFD-E) with voluntary access to running wheels for the last 6 weeks of experiments, running 6 h/night. Diet did not affect running time or distance. HFD mice weighed more than CTL after 18 weeks (p < 0.01). Quadriceps muscle TG was increased in running animals and in sedentary mice fed HFD for 18 weeks (p < 0.05). In exercised animals, markers of fat, Plin1, aP2, FSP27, and Fasn, were increased significantly in HFD groups. Ucp1 and Pgc1a, markers for brown fat, increased with exercise in the setting of high fat feeding. Fndc5, which encodes irisin, and CytC were sensitive to exercise regardless of diet. Plin5 was increased with HFD and unaffected by exercise; the respiratory exchange ratio was 15% lower in the 18-week HFD group compared with CTL (p < 0.001) and 10% lower in 18 weeks HFD-E compared with CTL-E (p < 0.001). Increased Ucp1 and Pgc1a in exercised muscle of running mice suggests that a beige/brown fat phenotype develops, which differs from the fat phenotype that induces insulin resistance in high fat feeding. This suggests that increased muscle lipid may develop a “brown” phenotype in the setting of endurance exercise training, a shift that is further promoted by HFD. PMID:27445983

  14. Differential expression of apolipoprotein D in male reproductive system of rats by high-fat diet.

    PubMed

    Lim, W; Bae, H; Song, G

    2016-11-01

    Apolipoprotein D, a 29-kDa secreted glycoprotein that belongs to the lipocalin superfamily, is widely expressed in various tissues and associated with lipid metabolism as a component of high-density lipoproteins. Although Apolipoprotein D binds to small hydrophobic ligands including cholesterol, little is known about effects of high-fat diet with cholesterol on expression of Apolipoprotein D in the male reproductive tract. Therefore, we investigated Apod expression in penises, prostate glands, and testes from rats fed a high-fat diet including a high amount of cholesterol. Our previous research indicated that a high-fat diet induces dyslipidemia leading to histological changes and dysfunction of male reproduction in rats. Consistent with these results, Apod mRNA expression was significantly (p < 0.001) decreased in penises and prostate glands (p < 0.01) and testes (p < 0.01) from rats fed a high-fat diet as compared with normal diet. In addition, Apod mRNA and protein were detected predominantly in urethral epithelium and penile follicle from rats. Moreover, changes in expression of specific microRNAs (miR-229b-3p, miR-423-3p, and miR-490-3p) regulating Apod in the penises and prostate glands were negatively associated with Apod expression. Collectively, results of this study suggest that Apod is a novel regulatory gene in the male reproductive system, especially in penises of rats fed a high-cholesterol diet, and that expression of Apod is regulated at the posttranscriptional level by target microRNAs.

  15. The adverse effects of high fat induced obesity on female reproductive cycle and hormones

    NASA Astrophysics Data System (ADS)

    Donthireddy, Laxminarasimha Reddy

    The prevalence of obesity, an established risk and progression factor for abnormal reproductive cycle and tissue damage in female mice. It leads to earlier puberty, menarche in young females and infertility. There are extensive range of consequences of obesity which includes type-2 diabetes, cardiovascular disease and insulin resistance. Obesity is the interaction between dietary intake, genes, life style and environment. The interplay of hormones estrogen, insulin, and leptin is well known on energy homeostasis and reproduction. The aim of this study is to determine the effect of high fat induced obesity on reproductive cycles and its hormonal abnormalities on mice model. Two week, 3 month and 8 month long normal (WT) and very high fat diet (VHFD) diet course is followed. When mice are fed with very high fat diet, there is a drastic increase in weight within the first week later. There was a significant (p<0.001) increase in leptin levels in 6 month VHFD treated animals. 2 week, 3 month and 6 month time interval pap smear test results showed number of cells, length of estrous cycle and phases of the estrous cycle changes with VHFD mice(n=30) compared to normal diet mice(n=10). These results also indicate that the changes in the reproductive cycles in VHFD treated female mice could be due to the changes in hormones. Histo-pathological analyses of kidney, ovary, liver, pancreas, heart and lungs showed remarkable changes in some tissue on exposure to very high fat. Highly deposited fat packets observed surrounding the hepatocytes and nerve cells.

  16. Adipokine production in mice fed high-fat diets containing different types of dietary fats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study compared high-fat diets containing different types of dietary fats with various levels of linoleic acid (18:2n6, LA) and a-linolenic acid (18:3n3, ALA) on adipokine production in male C57BL/6 mice. Three-week old mice were fed AIN93G diet (15% of energy from corn oil, control) or ...

  17. Maternal Deprivation Exacerbates the Response to a High Fat Diet in a Sexually Dimorphic Manner

    PubMed Central

    Mela, Virginia; Llorente-Berzal, Álvaro; Díaz, Francisca; Argente, Jesús; Viveros, María-Paz; Chowen, Julie A.

    2012-01-01

    Maternal deprivation (MD) during neonatal life has diverse long-term effects, including affectation of metabolism. Indeed, MD for 24 hours during the neonatal period reduces body weight throughout life when the animals are maintained on a normal diet. However, little information is available regarding how this early stress affects the response to increased metabolic challenges during postnatal life. We hypothesized that MD modifies the response to a high fat diet (HFD) and that this response differs between males and females. To address this question, both male and female Wistar rats were maternally deprived for 24 hours starting on the morning of postnatal day (PND) 9. Upon weaning on PND22 half of each group received a control diet (CD) and the other half HFD. MD rats of both sexes had significantly reduced accumulated food intake and weight gain compared to controls when raised on the CD. In contrast, when maintained on a HFD energy intake and weight gain did not differ between control and MD rats of either sex. However, high fat intake induced hyperleptinemia in MD rats as early as PND35, but not until PND85 in control males and control females did not become hyperleptinemic on the HFD even at PND102. High fat intake stimulated hypothalamic inflammatory markers in both male and female rats that had been exposed to MD, but not in controls. Reduced insulin sensitivity was observed only in MD males on the HFD. These results indicate that MD modifies the metabolic response to HFD intake, with this response being different between males and females. Thus, the development of obesity and secondary complications in response to high fat intake depends on numerous factors. PMID:23145019

  18. High fat diet exacerbates Alzheimer's disease-related pathology in APPswe/PS1 mice

    PubMed Central

    Thériault, Peter; ElAli, Ayman; Rivest, Serge

    2016-01-01

    Alzheimer's disease (AD) is mainly characterized by the accumulation and aggregation of amyloid-β (Aβ) peptides in brain parenchyma and cerebral microvasculature. Unfortunately, the exact causes of the disease are still unclear. However, blood-brain barrier (BBB) dysfunction and activation of inflammatory pathways are implicated in AD pathogenesis. Importantly, advanced age and high fat diet, two major risk factors associated with AD, were shown to deeply affect BBB function and modulate the immune response. As such, this study evaluated the impact of age and high fat diet on AD progression. For this purpose, 3 (i.e. young) and 12 (i.e. aged) months old APPswe/PS1 mice were fed for 4 months with a high fat diet (i.e. Western diet (WD)) or normal diet. Interestingly, neurobehavioral tests revealed that WD accelerates age-associated cognitive decline without affecting parenchymal Aβ. Nonetheless, WD decreases matrix metalloproteinase-9 enzymatic activity and brain-derived neurotrophic factor mRNA and protein levels in brain, suggesting loss of synaptic plasticity. In the periphery, WD promotes systemic inflammation by increasing the levels of blood-circulating monocytes and monocyte chemotactic protein-1 production, which is accompanied by an augmentation of oxidized-low density lipoprotein levels in blood circulation. At the BBB, WD potentiates the age-induced increase of Aβ 1-40 accumulation and exacerbates the oxidative stress, specifically in cerebral microvasculature. These effects were accompanied by the dysfunction of pericytes, thus altering BBB functionality without compromising its integrity. Our study provides new insights into the implication of high fat diet in accelerating the cognitive decline in AD. PMID:27661129

  19. Hormonal response to lipid and carbohydrate meals during the acute postprandial period

    PubMed Central

    2011-01-01

    Background Optimizing the hormonal environment during the postprandial period in favor of increased anabolism is of interest to many active individuals. Data are conflicting regarding the acute hormonal response to high fat and high carbohydrate feedings. Moreover, to our knowledge, no studies have compared the acute hormonal response to ingestion of lipid and carbohydrate meals of different size. Methods We compared the hormonal response to lipid and carbohydrate meals of different caloric content during the acute postprandial period. Nine healthy men (22 ± 2 years) consumed in a random order, cross-over design one of four meals/beverages during the morning hours in a rested and fasted state: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 0.5 hr, 1 hr, 2 hr, and 3 hr post meal. Samples were assayed for testosterone, cortisol, and insulin using ELISA techniques. Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was used to further analyze data. Results A meal × time effect (p = 0.0003) was noted for insulin, with values highest for the dextrose meals at the 0.5 hr and 1 hr times, and relatively unaffected by the lipid meals. No interaction (p = 0.98) or meal (p = 0.39) effect was noted for testosterone, nor was an interaction (p = 0.99) or meal (p = 0.65) effect noted for cortisol. However, a time effect was noted for both testosterone (p = 0.04) and cortisol (p < 0.0001), with values decreasing during the postprandial period. An AUC effect was noted for insulin (p = 0.001), with values higher for the dextrose meals compared to the lipid meals (p < 0.05). No AUC effect was noted for testosterone (p = 0.85) or cortisol (p = 0.84). Conclusions These data indicate that 1) little difference is noted in serum testosterone or cortisol during the acute postprandial period when healthy men consume lipid and dextrose meals of

  20. Effects of chicken-liver hydrolysates on lipid metabolism in a high-fat diet.

    PubMed

    Yang, Kou-Tai; Lin, Chen; Liu, Cheng-Wei; Chen, Yi-Chen

    2014-10-01

    The contents of free hydrophobic amino acids, taurine and carnosine/anserine were elevated after hydrolyzing chicken livers by pepsin and compared to dried chicken livers. Chicken-liver-hydrolysates (CLHs) exhibited in vitro inhibitory lipase activity and bile-acid binding ability (p<0.05). Forty-eight male hamsters were assigned randomly to the following groups: (1) chow diet; (2) high-fat diet (HFD); (3) HFD and 100 mg CLH/kg BW; (4) HFD and 200 mg CLH/kg BW; (5) HFD and 400 mg CLH/kg BW; (6) HFD and 200 mg carnosine/kg BW. CLHs alleviated (p<0.05) serum oxidative stress and improved (p<0.05) the serum lipid profile in the high-fat dietary groups; meanwhile, improved (p<0.05) antioxidant abilities and decreased (p<0.05) lipid accumulation, oxidative stress and TNF-α/IL-1β levels in the livers. These benefits might result from regulations of lipid homeostasis and increased faecal bile-acid outputs (p<0.05). Hence, lipid-homeostasis and antioxidant abilities of CLHs in the high-fat dietary habit were demonstrated and were similar to pure carnosine.

  1. Hypocholesterolemic effect of daily fisetin supplementation in high fat fed Sprague-Dawley rats.

    PubMed

    Shin, Min-Jeong; Cho, Yoonsu; Moon, Jiyoung; Jeon, Hyun Ju; Lee, Seung-Min; Chung, Ji Hyung

    2013-07-01

    We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet-induced hypercholesterolemia, and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect. Blood lipid profile, hepatic cholesterol content, as well as gene expressions in cholesterol metabolism were examined. Elevated levels of total cholesterol and LDL-cholesterol, along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin. The high fat diet significantly decreased hepatic mRNA levels of LDLR, SREBP2, HMGCR and PCSK9 in comparison to the control diet, however, fisetin did not further elicit any changes in mRNA levels of the same genes. The high fat diet dramatically increased the transcript levels of CYP7A1, which was subsequently reversed by the fisetin. In HepG2 cells, fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR. In conclusion, fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism.

  2. Gestational exercise protects adult male offspring from high-fat diet induced hepatic steatosis

    PubMed Central

    Sheldon, Ryan D.; Blaize, A. Nicole; Fletcher, Justin A.; Pearson, Kevin J.; Donkin, Shawn; Newcomer, Sean C.; Rector, R. Scott

    2015-01-01

    Background & Aims Mounting evidence indicates that maternal exercise confers protection to adult offspring against various diseases. Here we hypothesized that maternal exercise during gestation would reduce high fat diet (HFD) induced hepatic steatosis in adult rat offspring. Methods Following conception, pregnant dams were divided into either voluntary wheel running exercise (GE) or wheel-locked sedentary (GS) groups throughout gestation (days 4-21). Post-weaning, offspring received either normal chow diet (ND; 10% fat, 70% carbohydrate, 20% protein) or high-fat diet (HFD; 45% fat, 35% carbohydrate, and 20% protein) until sacrifice at 4-or 8-months of age. Results GE did not affect offspring birth weight or litter size. HFD feeding in offspring increased weight gain, % body fat, and glucose tolerance test area under the curve (GTT-AUC). Male offspring from GE dams had reduced % body fat across all ages (p < 0.05). In addition, 8-mo male offspring from GE dams were protected against HFD-induced hepatic steatosis, which was associated with increased markers of hepatic mitochondrial biogenesis (PGC-1α and TFAM), autophagic potential (ATG12:ATG5 conjugation) and hepatic triacylglycerol secretion (MTTP). Conclusions The current study provides the first evidence that gestational exercise can reduce susceptibility to high fat diet induced hepatic steatosis in adult male offspring. PMID:26325536

  3. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

    PubMed Central

    Lee, Seong-Jong; Han, Jong-Min; Lee, Jin-Seok; Son, Chang-Gue; Im, Hwi-Jin; Jo, Hyun-Kyung; Yoo, Ho-Ryong; Kim, Yoon-Sik; Seol, In-Chan

    2015-01-01

    The medicinal plants Artemisia iwayomogi (A. iwayomogi) and Curcuma longa (C. longa) radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM). In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE) on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group) were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group) were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg) or curcumin (50 mg/kg). Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides), glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα). The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model. PMID:26508977

  4. Voglibose administration regulates body weight and energy intake in high fat-induced obese mice.

    PubMed

    Do, Hyun Ju; Jin, Taeon; Chung, Ji Hyung; Hwang, Ji Won; Shin, Min-Jeong

    2014-01-17

    We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12 weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.

  5. High-fat diet induced isoform changes of the Parkinson's disease protein DJ-1.

    PubMed

    Poschmann, Gereon; Seyfarth, Katrin; Besong Agbo, Daniela; Klafki, Hans-Wolfgang; Rozman, Jan; Wurst, Wolfgang; Wiltfang, Jens; Meyer, Helmut E; Klingenspor, Martin; Stühler, Kai

    2014-05-02

    Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights into the underlying processes involved in energy intake and weight gain, we compared hypothalamic tissue of mice kept on a high-fat or control diet for 10 days by a proteomic approach. Using two-dimensional difference gel electrophoresis in combination with LC-MS/MS, we observed significant abundance changes in 15 protein spots. One isoform of the protein DJ-1 was elevated in the high-fat diet group in three different mouse strains SWR/J, C57BL/6N, and AKR/J analyzed. Large-scale validation of DJ-1 isoforms in individual samples and tissues confirmed a shift in the pattern of DJ-1 isoforms toward more acidic isoforms in several brain and peripheral tissues after feeding a high-fat diet for 10 days. The identification of oxidation of cysteine 106 as well as 2-succinyl modification of the same residue by mass spectrometry not only explains the isoelectric shift of DJ-1 but also links our results to similar shifts of DJ-1 observed in neurodegenerative disease states under oxidative stress. We hypothesize that DJ-1 is a common physiological sensor involved in both nutrition-induced effects and neurodegenerative disease states.

  6. A High Fat Diet and NAD+ Rescue Premature Aging in Cockayne Syndrome

    PubMed Central

    Scheibye-Knudsen, Morten; Mitchell, Sarah J.; Fang, Evandro F.; Iyama, Teruaki; Ward, Theresa; Wang, James; Dunn, Christopher A.; Singh, Nagendra; Veith, Sebastian; Hasan, M. Mahdi; Mangerich, Aswin; Wilson, Mark A.; Mattson, Mark P.; Bergersen, Linda H.; Cogger, Victoria C.; Warren, Alessandra; Le Couteur, David G.; Moaddel, Ruin; Wilson, David M.; Croteau, Deborah L.; de Cabo, Rafael; Bohr, Vilhelm A.

    2014-01-01

    Summary Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in the genes encoding the DNA repair proteins CSA or CSB. Csbm/m mice were given a high fat, caloric restricted or resveratrol supplemented diet. The high fat diet rescued the phenotype of Csbm/m mice at the metabolic, transcriptomic and behavioral levels. Additional analysis suggests that the premature aging seen in CS mice, nematodes and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high fat diet; and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB is able to displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS. PMID:25440059

  7. Cardiovascular protection of deep-seawater drinking water in high-fat/cholesterol fed hamsters.

    PubMed

    Hsu, Chin-Lin; Chang, Yuan-Yen; Chiu, Chih-Hsien; Yang, Kuo-Tai; Wang, Yu; Fu, Shih-Guei; Chen, Yi-Chen

    2011-08-01

    Cardiovascular protection of deep-seawater (DSW) drinking water was assessed using high-fat/cholesterol-fed hamsters in this study. All hamsters were fed a high-fat/cholesterol diet (12% fat/0.2% cholesterol), and drinking solutions were normal distiled water (NDW, hardness: 2.48ppm), DSW300 (hardness: 324.5ppm), DSW900 (hardness: 858.5ppm), and DSW1500 (hardness: 1569.0ppm), respectively. After a 6-week feeding period, body weight, heart rates, and blood pressures of hamsters were not influenced by DSW drinking waters. Serum total cholesterol (TC), triacylglycerol (TAG), atherogenic index, and malondialdehyde (MDA) levels were decreased (p<0.05) in the DSW-drinking-water groups, as compared to those in the NDW group. Additionally, increased (p<0.05) serum Trolox equivalent antioxidant capacity (TEAC), and faecal TC, TAG, and bile acid outputs were measured in the DSW-drinking-water groups. Hepatic low-density-lipoprotein receptor (LDL receptor) and cholesterol-7α-hydroxylase (CYP7A1) gene expressions were upregulated (p<0.05) by DSW drinking waters. These results demonstrate that DSW drinking water benefits the attenuation of high-fat/cholesterol-diet-induced cardiovascular disorders in hamsters.

  8. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

    PubMed Central

    Martins, Fernando; Campos, Dijon Henrique Salomé; Pagan, Luana Urbano; Martinez, Paula Felippe; Okoshi, Katashi; Okoshi, Marina Politi; Padovani, Carlos Roberto; de Souza, Albert Schiaveto; Cicogna, Antonio Carlos; de Oliveira-Junior, Silvio Assis

    2015-01-01

    Background Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity. Objective To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet. Methods Sixteen Wistar rats were used, distributed into two groups, the control (C) group, treated with isocaloric diet (2.93 kcal/g) and an obese (OB) group, treated with high-fat diet (3.64 kcal/g). The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed. Results High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained. Conclusions It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity. PMID:26291841

  9. Neonatal parathion exposure and interactions with a high-fat diet in adulthood: Adenylyl cyclase-mediated cell signaling in heart, liver and cerebellum.

    PubMed

    Adigun, Abayomi A; Wrench, Nicola; Levin, Edward D; Seidler, Frederic J; Slotkin, Theodore A

    2010-04-05

    Organophosphates are developmental neurotoxicants but recent evidence points to additional adverse effects on metabolism and cardiovascular function. One common mechanism is disrupted cell signaling mediated through cyclic AMP, targeting neurohumoral receptors, G-proteins and adenylyl cyclase (AC) itself. Earlier, we showed that neonatal parathion evokes later upregulation of the hepatic AC pathway in adolescence but that the effect wanes by young adulthood; nevertheless metabolic changes resembling prediabetes persist. Here, we administered parathion to neonatal rats (postnatal days 1-4, 0.1 or 0.2 mg/kg/day), straddling the threshold for cholinesterase inhibition, but we extended the studies to much later, 5 months of age. In addition, we investigated whether metabolic challenge imposed by consuming a high-fat diet for 7 weeks would exacerbate neonatal parathion's effects. Parathion alone increased the expression or function of G(i), thus reducing AC responses to fluoride. Receptors controlling AC activity were also affected: beta-adrenergic receptors (betaARs) in skeletal muscle were increased, whereas those in the heart were decreased, and the latter also showed an elevation of m(2)-muscarinic acetylcholine receptors, which inhibit AC. The high-fat diet also induced changes in AC signaling, enhancing the hepatic AC response to glucagon while impairing the cardiac response to fluoride or forskolin, and suppressing betaARs and m(2)-muscarinic receptors; the only change in the cerebellum was a decrease in betaARs. Although there were no significant interactions between neonatal parathion exposure and a high-fat diet, their convergent effects on the same signaling cascade indicate that early OP exposure, separately or combination with dietary factors, may contribute to the worldwide increase in the incidence of obesity and diabetes.

  10. Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet.

    PubMed

    Raso, Giuseppina Mattace; Simeoli, Raffaele; Iacono, Anna; Santoro, Anna; Amero, Paola; Paciello, Orlando; Russo, Roberto; D'Agostino, Giuseppe; Di Costanzo, Margherita; Canani, Roberto Berni; Calignano, Antonio; Meli, Rosaria

    2014-01-01

    Insulin resistance (IR) has been identified as crucial pathophysiological factor in the development and progression of non-alcoholic fatty liver disease (NAFLD). Although mounting evidence suggests that perturbation of gut microflora exacerbates the severity of chronic liver diseases, therapeutic approaches using synbiotic has remained overlooked. Here, we show that a synbiotic composed by Lactobacillus paracasei B21060 plus arabinogalactan and fructo-oligosaccharides lessens NAFLD progression in a rat model of high fat feeding. IR and steatosis were induced by administration of high fat diet (HFD) for 6 weeks. Steatosis and hepatic inflammation, Toll-like receptor (TLR) pattern, glucose tolerance, insulin signaling and gut permeability were studied. Liver inflammatory markers were down-regulated in rats receiving the synbiotic, along with an increased expression of nuclear peroxisome proliferator-activated receptors and expression of downstream target genes. The synbiotic improved many aspects of IR, such as fasting response, hormonal homeostasis and glycemic control. Indeed it prevented the impairment of hepatic insulin signaling, reducing the phosphorylation of insulin receptor substrate-1 in Ser 307 and down-regulating suppressor of cytokine signaling 3. Gene expression analysis revealed that in the liver the synbiotic reduced cytokines synthesis and restored the HFD-dysregulated TLR 2, 4 and 9 mRNAs toward a physiological level of expression. The synbiotic preserved gut barrier integrity and reduced the relative amount of Gram-negative Enterobacteriales and Escherichia coli in colonic mucosa. Overall, our data indicate that the L. paracasei B21060 based synbiotic is effective in reducing the severity of liver injury and IR associated with high fat intake, suggesting its possible therapeutic/preventive clinical utilization.

  11. Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin; Qi, Cuijuan; Wang, Tong

    2015-10-01

    Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p < 0.05). The expression of POMC and MC4R genes were significantly increased in offspring exposed to FS diet during gestation, lactation and into 32-week age (p < 0.05). Consistently, hypomethylation of POMC promoter in the hypothalamus occurred in the FS diet offspring (p < 0.05), compared with the C group. However, no methylation was detected of MC4R promoter in both the two groups. Furthermore, POMC-specific methylation (%) was negatively associated with glucose response to a glucose load (r = -0.273, p = 0.039). Maternal and post-weaning high-fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

  12. Neonatal Parathion Exposure and Interactions with a High-Fat Diet in Adulthood: Adenylyl Cyclase-Mediated Cell Signaling in Heart, Liver and Cerebellum

    PubMed Central

    Adigun, Abayomi A.; Wrench, Nicola; Levin, Edward D.; Seidler, Frederic J.; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence points to additional adverse effects on metabolism and cardiovascular function. One common mechanism is disrupted cell signaling mediated through cyclic AMP, targeting neurohumoral receptors, G-proteins and adenylyl cyclase (AC) itself. Earlier, we showed that neonatal parathion evokes later upregulation of the hepatic AC pathway in adolescence but that the effect wanes by young adulthood; nevertheless metabolic changes resembling prediabetes persist. Here, we administered parathion to neonatal rats (postnatal days 1-4, 0.1 or 0.2 mg/kg/day), straddling the threshold for cholinesterase inhibition, but we extended the studies to much later, 5 months of age. In addition, we investigated whether metabolic challenge imposed by consuming a high-fat diet for 7 weeks would exacerbate neonatal parathion’s effects. Parathion alone increased the expression or function of Gi, thus reducing AC responses to fluoride. Receptors controlling AC activity were also affected: β-adrenergic receptors (βARs) in skeletal muscle were increased, whereas those in the heart were decreased, and the latter also showed an elevation of m2-muscarinic acetylcholine receptors, which inhibit AC. The high-fat diet also induced changes in AC signaling, enhancing the hepatic AC response to glucagon while impairing the cardiac response to fluoride or forskolin, and suppressing βARs and m2-muscarinic receptors; the only change in the cerebellum was a decrease in βARs. Although there were no significant interactions between neonatal parathion exposure and a high-fat diet, their convergent effects on the same signaling cascade indicate that early OP exposure, separately or combination with dietary factors, may contribute to the worldwide increase in the incidence of obesity and diabetes. PMID:20074626

  13. Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

    PubMed

    Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

    2013-08-01

    Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes.

  14. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    PubMed

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release.

  15. Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice.

    PubMed

    Kuhn, Emmanuelle; Bourgeois, Christine; Keo, Vixra; Viengchareun, Say; Muscat, Adeline; Meduri, Geri; Le Menuet, Damien; Fève, Bruno; Lombès, Marc

    2014-01-01

    The mineralocorticoid receptor (MR) exerts proadipogenic and antithermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high-fat diet (HFD) for 16 wk. Tg mice had a lower body weight gain than WT animals and exhibited a relative resistance to HFD-induced obesity. This was associated with a decrease in fat mass, an increased population of smaller adipocytes, and an improved glucose tolerance compared with WT animals. Quantitative RT-PCR studies revealed decreased expression of PPARγ2, a master adipogenic gene, and of glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1, consistent with an impaired local glucocorticoid signaling in adipose tissues (AT). This paradoxical resistance to HFD-induced obesity was not related to an adipogenesis defect since differentiation capacity of Tg preadipocytes isolated from stroma-vascular fractions was unaltered, suggesting that other nonadipocyte factors might compromise AT development. Although AT macrophage infiltration was not different between genotypes, Tg mice exhibited a distinct macrophage polarization, as revealed by FACS analysis and CD11c/CD206 expression studies. We further demonstrated that Tg macrophage-conditioned medium partially impaired preadipocyte differentiation. Therefore, we propose that modification of M1/M2 polarization of hMR-overexpressing macrophages could account in part for the metabolic phenotype of Tg mice. Collectively, our results provide evidence that MR exerts a pivotal immunometabolic role by controlling adipocyte differentiation processes directly but also indirectly through macrophage polarization regulation. Our findings should be taken into account for the pharmacological treatment of metabolic disorders.

  16. Grape pomace and grape pomace extract improve insulin signaling in high-fat-fructose fed rat-induced metabolic syndrome.

    PubMed

    Rodriguez Lanzi, Cecilia; Perdicaro, Diahann Jeanette; Antoniolli, Andrea; Fontana, Ariel Ramón; Miatello, Roberto Miguel; Bottini, Rubén; Vazquez Prieto, Marcela Alejandra

    2016-03-01

    In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds.

  17. Behavioural effects of high fat diet in a mutant mouse model for the schizophrenia risk gene neuregulin 1.

    PubMed

    Holm-Hansen, S; Low, J K; Zieba, J; Gjedde, A; Bergersen, L H; Karl, T

    2016-03-01

    Schizophrenia patients are often obese or overweight and poor dietary choices appear to be a factor in this phenomenon. Poor diet has been found to have complex consequences for the mental state of patients. Thus, this study investigated whether an unhealthy diet [i.e. high fat diet (HFD)] impacts on the behaviour of a genetic mouse model for the schizophrenia risk gene neuregulin 1 (i.e. transmembrane domain Nrg1 mutant mice: Nrg1 HET). Female Nrg1 HET and wild-type-like littermates (WT) were fed with either HFD or a control chow diet. The mice were tested for baseline (e.g. anxiety) and schizophrenia-relevant behaviours after 7 weeks of diet exposure. HFD increased body weight and impaired glucose tolerance in all mice. Only Nrg1 females on HFD displayed a hyper-locomotive phenotype as locomotion-suppressive effects of HFD were only evident in WT mice. HFD also induced an anxiety-like response and increased freezing in the context and the cued version of the fear conditioning task. Importantly, CHOW-fed Nrg1 females displayed impaired social recognition memory, which was absent in HFD-fed mutants. Sensorimotor gating deficits of Nrg1 females were not affected by diet. In summary, HFD had complex effects on the behavioural phenotype of test mice and attenuated particular cognitive deficits of Nrg1 mutant females. This topic requires further investigations thereby also considering other dietary factors of relevance for schizophrenia as well as interactive effects of diet with medication and sex.

  18. Protein and fat modify the glycaemic and insulinaemic responses to a mashed potato-based meal.

    PubMed

    Hätönen, Katja A; Virtamo, Jarmo; Eriksson, Johan G; Sinkko, Harri K; Sundvall, Jouko E; Valsta, Liisa M

    2011-07-01

    Potatoes, especially mashed potatoes, are known to result in high glycaemic and insulinaemic responses. However, in most meals, potatoes are accompanied by other foods. The objective of the present study was to investigate how glycaemic and insulinaemic responses to a mashed potato meal changed when a high-fat food (rapeseed oil), a high-protein food (chicken breast) and/or salad were added to the meal. Healthy subjects (n 11) ingested the test meals once and the reference food (glucose solution) twice in a random order at 1-week intervals. Capillary blood samples were then drawn for 2 h, and glucose and insulin were analysed. The 2 h glycaemic responses to six mashed potato-containing meals varied more than twofold. The glycaemic index (GI) of pure mashed potato was 108, whereas combined with chicken breast, rapeseed oil and salad, it was only 54. The latter GI also differed considerably from its predicted value of 103, which was based on the individual GI of the components of the meal. The insulinaemic indices of the mashed potato-based meals varied between 94 and 148. Chicken breast in the meal increased the insulinaemic response, and rapeseed oil diminished it. However, the insulinaemic response to mashed potato with chicken breast and rapeseed oil was lower than that to mashed potato alone. In conclusion, the protein, fat and salad contents of a meal exert considerable influence on the glycaemic and insulinaemic responses to mashed potatoes. Furthermore, the estimation of the GI of a mixed meal by calculation is imprecise.

  19. Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice.

    PubMed

    Sim, Mi-Ok; Ham, Ju Ri; Lee, Hae-In; Seo, Kwon-Il; Lee, Mi-Kyung

    2014-06-05

    This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid β-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.

  20. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism.

    PubMed

    Deminice, Rafael; da Silva, Robin P; Lamarre, Simon G; Kelly, Karen B; Jacobs, René L; Brosnan, Margaret E; Brosnan, John T

    2015-04-01

    The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.

  1. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    PubMed

    Boa, Beatriz C S; Souza, Maria das Graças C; Leite, Richard D; da Silva, Simone V; Barja-Fidalgo, Thereza Christina; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

    2014-01-01

    Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10(-8) M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10(-6) M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10(-4) M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial

  2. Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters.

    PubMed

    Lomba, Almudena; Martínez, J Alfredo; García-Díaz, Diego F; Paternain, Laura; Marti, Amelia; Campión, Javier; Milagro, Fermín I

    2010-01-01

    Experimental studies have demonstrated that dietary macronutrient distribution plays an important role in insulin regulation, a risk factor associated to obesity, diabetes and other metabolic disorders. To assess whether the macronutrient composition of the diet could be related to obesity onset by affecting the epigenetic regulation of gene expression, we investigated in rats the metabolic effects of two pair-fed isocaloric diets: control (rich in carbohydrates) and high fat diet (rich in fat; HFD). Compared to controls, HFD induced higher weight gain and adiposity and impaired glucose tolerance, which was accompanied by a slight increase in adiponectin levels and liver steatosis. Epididymal adipose tissue expression of the fatty acid synthase (FASN) gene and NADH dehydrogenase (ubiquinone) 1β-subcomplex 6 (NDUFB6) were significantly reduced in HFD group. These variations in mRNA levels were accompanied by changes in the methylation patterns of several CpG islands located in the promoter region of these genes. However, no correlations were found between gene expression and the methylation status. These results suggest that high fat intake produces overweighted rats independently of total energy intake. These diets could also induce some epigenetic changes in the promoters of key genes that could influence gene expression and may be behind metabolic alterations.

  3. Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice

    PubMed Central

    Bardova, Kristina; Gardlo, Alzbeta; Rombaldova, Martina; Kuda, Ondrej; Rossmeisl, Martin; Kopecky, Jan

    2016-01-01

    Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. PMID:27183228

  4. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

    PubMed Central

    2013-01-01

    Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1). Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman

  5. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood

    PubMed Central

    de Fante, Thaís; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; de Souza, Monique; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  6. Effect of Morinda citrifolia (Noni) Fruit Juice on High Fat Diet Induced Dyslipidemia in Rats

    PubMed Central

    Shoeb, Ahsan; Alwar, M.C.; Gokul, P.

    2016-01-01

    Introduction The medicinal value of Morinda citrifolia L. (commonly known as Noni) has been explored in ancient folk remedies with a wide range of therapeutic utility, including antibacterial, antiviral, antifungal, antitumour, analgesic, hypotensive, anti-inflammatory and immune enhancing effects. Aim The present study was designed to evaluate the effects of Noni fruit juice on serum lipid profile in high fat diet induced murine model of dyslipidemia. Materials and Methods Hyperlipidemia was induced by feeding a cholesterol rich high fat diet for 45 days in wistar albino rats of either sex (n=8). Noni fruit juice administered at 50mg/kg/day and 100mg/kg/day, per oral, was compared with the standard drug Atorvastatin (10mg/kg/day, oral) fed for the latter 30 days. The blood samples were then sent for complete blood lipid profile, after 30 days of treatment. The data presented as mean ± SEM was analyzed using one-way ANOVA followed by Tukey’s post-hoc test. The p <0.05 was considered as statistically significant. Results The Noni fruit juice treated group showed a significant decrease in the total cholesterol, triglycerides and very low density lipoprotein - Cholesterol at both the doses when compared to the disease control (p<0.05). However, the decrease in the TC (102.75±9.79 mg/dL) and LDL-C (47.87±7.47 mg/dL) levels observed with the noni fruit juice at the 50mg/kg dose employed, failed to show a statistical significance when compared to atorvastatin. Conclusion The present study provides evidence for the hypolipidemic activity of Noni fruit juice in high fat diet induced hyperlipidemia in rats. PMID:27190827

  7. Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

    PubMed

    Alsanea, Sary; Gao, Mingming; Liu, Dexi

    2017-02-14

    Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

  8. Fasting and sampling time affect liver gene expression of high-fat diet-fed mice.

    PubMed

    Lee, C Y

    2010-05-01

    Several physiological and biological variables are known to affect peroxisome proliferator-activated receptor (PPAR)-α-dependent signaling pathway and plasma biochemical profiles. However, less is known about the effect of these variables on high-fat diet-fed mice. In a 5-week study, C57BL/6 mice were divided into control (C) and high-fat diet-fed (H) groups, whereby before dissection, each group was subdivided into non-fasted (nC and nH) and a 15-h fasted mice (fC and fH) killed in the early light cycle, and a 15-h fasted mice (eC and eH) killed in the late phase of the light cycle. Liver and blood from the vena cava were collected. Non-fasted nC and nH mice have a marginal difference in their body weight gain, whereas significant differences were found for fasted mice. In nH mice, PPAR-α, acyl-CoA oxidase and insulin-like growth factor-binding protein expressions were significantly elevated, in contrast to fatty acid synthase (Fasn), stearoyl CoA-desaturase (SCD)-1, and elongase (ELOVL)-6 expressions. Fasn was profoundly induced in fH mice, while decreased sterol regulatory-binding protein-1 and SCD-1 were found only in eH mice. Different from the gene expression profiles, plasma total cholesterol level of the eH mice was higher than controls, whereas nH mice have increased plasma non-esterified fatty acids. Only glucose level of the fH mice was higher than that observed for controls. Results showed that fasting and sampling time have significantly affected liver gene expression and plasma biochemical indices of the high-fat diet-treated mice. An overlook in these aspects can cause serious discrepancies in the experimental data and their interpretations.

  9. Endurance capacity and high-intensity exercise performance responses to a high fat diet.

    PubMed

    Fleming, Jesse; Sharman, Matthew J; Avery, Neva G; Love, Dawn M; Gómez, Ana L; Scheett, Timothy P; Kraemer, William J; Volek, Jeff S

    2003-12-01

    The effects of adaptation to a high-fat diet on endurance performance are equivocal, and there is little data regarding the effects on high-intensity exercise performance. This study examined the effects of a high-fat/moderate protein diet on submaximal, maximal, and supramaximal performance. Twenty non-highly trained men were assigned to either a high-fat/moderate protein (HFMP; 61% fat diet) (n = 12) or a control (C; 25% fat) group (n = 8). A maximal oxygen consumption test, two 30-s Wingate anaerobic tests, and a 45-min timed ride were performed before and after 6 weeks of diet and training. Body mass decreased significantly (-2.2 kg; p < or = .05) in HFMP subjects. Maximal oxygen consumption significantly decreased in the HFMP group (3.5 +/- 0.14 to 3.27 +/- 0.09 L x min(-1)) but was unaffected when corrected for body mass. Perceived exertion was significantly higher during this test in the HFMP group. Main time effects indicated that peak and mean power decreased significantly during bout 1 of the Wingate sprints in the HFMP (-10 and -20%, respectively) group but not the C (-8 and -16%, respectively) group. Only peak power was lower during bout 1 in the HFMP group when corrected for body mass. Despite significantly reduced RER values in the HFMP group during the 45-min cycling bout, work output was significantly decreased (-18%). Adaptation to a 6-week HFMP diet in non-highly trained men resulted in increased fat oxidation during exercise and small decrements in peak power output and endurance performance. These deleterious effects on exercise performance may be accounted for in part by a reduction in body mass and/or increased ratings of perceived exertion.

  10. Dietary krill oil supplementation reduces hepatic steatosis, glycemia, and hypercholesterolemia in high-fat-fed mice.

    PubMed

    Tandy, Sally; Chung, Rosanna W S; Wat, Elaine; Kamili, Alvin; Berge, Kjetil; Griinari, Mikko; Cohn, Jeffrey S

    2009-10-14

    Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease.

  11. Longitudinal analysis of short-term high-fat diet on endothelial senescence in baboons

    PubMed Central

    Shi, Qiang; Hornsby, Peter J; Meng, Qinghe; VandeBerg, Jane F; VandeBerg, John L

    2013-01-01

    A high-fat diet is a major risk factor for atherosclerosis. We conducted a longitudinal investigation to determine whether vascular endothelial senescence is involved in the mechanism by which a high-fat diet promotes atherogenesis. We challenged 10 baboons (Papio sp.) with a high-cholesterol high-fat (HCHF) diet for 7 weeks. In addition to multiple changes in plasma lipid profiles, inflammatory status, and endothelial functions in each individual, we found that levels of total serum cholesterol (TSC) and monocyte chemotactic protein-1 (MCP-1) were negatively and significantly correlated with endothelial nitric oxide synthase (eNOS) levels in endothelial cells while the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were significantly correlated with nitric oxide levels in plasma within this time window. Most important, we observed that senescence-associated β-galactosidase (SA-β-gal) activities in endothelial cells harvested at 7 weeks after initiation of HCHF diet were significantly elevated by comparison with cells isolated from the same animals prior to dietary challenge. The SA-β-gal activities correlated significantly with the elevations of TSC, LDL-cholesterol, HDL-cholesterol, and IL-8 after 7 weeks of HCHF diet and with the changes of TSC and TNF-α levels after 3 weeks of HCHF diet. Our data indicate that the HCHF diet caused hyperlipidemia and prominent inflammation, which subsequently will cause endothelial dysfunction and promote senescence. The present study is the first to demonstrate the sequential and interactive changes as a consequence of an HCHF dietary challenge and establish a potential mechanism underlying the etiology of diet-induced atherogenesis in a nonhuman primate. PMID:23991345

  12. Impact of chromium histidinate on high fat diet induced obesity in rats

    PubMed Central

    2011-01-01

    Background Chromium (Cr) is an essential trace element that has garnered interest for use as a weight loss aid, but its molecular mechanism in obesity is not clear. In this study, an attempt has been made to investigate the effects of chromium histidinate (CrHis) on glucose transporter-2 (GLUT-2), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB p65) and the oxidative stress marker 4-hydroxynonenal adducts (HNE) expressions in liver of rats fed high fat diet (HFD). Methods Male Wistar rats (n = 40, 8 wk-old) were divided into four groups. Group I was fed a standard diet (12% of calories as fat); Group II was fed a standard diet and supplemented with 110 μg CrHis/kg BW/d; Group III was fed a HFD (40% of calories as fat); Group IV was fed HFD and supplemented with 110 μg CrHis/kg BW/d. Results Rats fed HFD possessed greater serum insulin (40 vs.33 pmol/L) and glucose (158 vs. 143 mg/dL) concentration and less liver Cr (44 vs.82 μg/g) concentration than rats fed the control diet. However, rats supplemented with CrHis had greater liver Cr and serum insulin and lower glucose concentration in rats fed HFD (P < 0.05). The hepatic nuclear factor-kappa B (NF-κB p65) and HNE were increased in high fat group compared to control group, but reduced by the CrHis administration (P < 0.05). The levels of hepatic Nrf2 and HO-1 were increased by supplementation of CrHis (P < 0.05). Conclusion These findings demonstrate that supplementation of CrHis is protective against obesity, at least in part, through Nrf2-mediated induction of HO-1 in rats fed high fat diet. PMID:21539728

  13. Caveolin expression and activation in retroperitoneal and subcutaneous adipocytes: influence of a high-fat diet.

    PubMed

    Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

    2010-10-01

    The effect of a high-fat diet on the expression of the three main isoforms of caveolins in adipocytes isolated from rat retroperitoneal and subcutaneous white adipose tissue was investigated. Two distinct phases can be distinguished on a time-dependent response in adipocytes from both locations. The early stage affects only to retroperitoneal adipocytes and implies caveolin-1 activation and caveolin-2 inactivation, together with increased expression of insulin signaling intermediaries. This initial response would be aimed to counterbalance the energy overload. Continued exposure to the high-fat diet produces an increase in circulating glucose and insulin levels, inducing a late stage in which adipocytes from both locations are affected. This late stage is characterized by general increased caveolin-1 and caveolin-2 expression; while on the other hand, the insulin signaling intermediaries are downregulated, with the noticeable exception of GLUT-4, whose expression remains high. Therefore, it seems that at this stage caveolins and GLUT-4 are regulated independently of the insulin pathway, through a mechanism that could be mediated by inflammation and oxidative stress associated with obesity. Although this GLUT-4 upregulation suggests a response against the raise in circulating glucose, this might not be the case, since the developing insulin resistance at this stage indicates a prediabetic state. We have also found that the high-fat diet is able to induce the expression of muscle-specific caveolin-3 in retroperitoneal adipocytes since the initial phase. This observation is similar to what we reported previously in skeletal muscle (Gómez-Ruiz et al., 2009, FEBS Lett 583:3259-3264), suggesting a similar regulatory mechanism for this isoform.

  14. Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases

    PubMed Central

    Zhang, Mei; Yang, Xiao-Jiao

    2016-01-01

    Along with the rapid development of society, lifestyles and diets have gradually changed. Due to overwhelming material abundance, high fat, high sugar and high protein diets are common. Numerous studies have determined that diet and its impact on gut microbiota are closely related to obesity and metabolic diseases. Different dietary components affect gut microbiota, thus impacting gastrointestinal disease occurrence and development. A large number of related studies are progressing rapidly. Gut microbiota may be an important intermediate link, causing gastrointestinal diseases under the influence of changes in diet and genetic predisposition. To promote healthy gut microbiota and to prevent and cure gastrointestinal diseases, diets should be improved and supplemented with probiotics. PMID:27833381

  15. Blueberry intervention improves vascular reactivity and lowers blood pressure in high-fat-, high-cholesterol-fed rats.

    PubMed

    Rodriguez-Mateos, Ana; Ishisaka, Akari; Mawatari, Kazuaki; Vidal-Diez, Alberto; Spencer, Jeremy P E; Terao, Junji

    2013-05-28

    Growing evidence suggests that intake of flavonoid-containing foods may exert cardiovascular benefits in human subjects. We have investigated the effects of a 10-week blueberry (BB) supplementation on blood pressure (BP) and vascular reactivity in rats fed a high-fat/high-cholesterol diet, known to induce endothelial dysfunction. Rats were randomly assigned to follow a control chow diet, a chow diet supplemented with 2 % (w/w) BB, a high-fat diet (10 % lard; 0·5 % cholesterol) or the high fat plus BB for 10 weeks. Rats supplemented with BB showed significant reductions in systolic BP (SBP) of 11 and 14 %, at weeks 8 and 10, respectively, relative to rats fed the control chow diet (week 8 SBP: 107·5 (SEM 4·7) v. 122·2 (SEM 2·1) mmHg, P= 0·018; week 10 SBP: 115·0 (SEM 3·1) v. 132·7 (SEM 1·5) mmHg, P< 0·0001). Furthermore, SBP was reduced by 14 % in rats fed with the high fat plus 2 % BB diet at week 10, compared to those on the high-fat diet only (SBP: 118·2 (SEM 3·6) v. 139·5 (SEM 4·5) mmHg, P< 0·0001). Aortas harvested from BB-fed animals exhibited significantly reduced contractile responses (to L-phenylephrine) compared to those fed the control chow or high-fat diets. Furthermore, in rats fed with high fat supplemented with BB, aorta relaxation was significantly greater in response to acetylcholine compared to animals fed with the fat diet. These data suggest that BB consumption can lower BP and improve endothelial dysfunction induced by a high fat, high cholesterol containing diet.

  16. The cardioprotective effects of fish oil during pressure overload are blocked by high fat intake: role of cardiac phospholipid remodeling.

    PubMed

    Shah, Keyur B; Duda, Monika K; O'Shea, Karen M; Sparagna, Genevieve C; Chess, David J; Khairallah, Ramzi J; Robillard-Frayne, Isabelle; Xu, Wenhong; Murphy, Robert C; Des Rosiers, Christine; Stanley, William C

    2009-09-01

    Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil may prevent development of heart failure through alterations in cardiac phospholipids that favorably impact inflammation and energy metabolism. A high-fat diet may block these effects in chronically stressed myocardium. Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to pressure overload by constriction of the abdominal aorta. Animals were fed: (1) standard diet (10% of energy from fat), (2) standard diet with EPA+DHA (2.3% of energy intake as EPA+DHA), (3) high fat (60% fat); or (4) high fat with EPA+DHA. Pressure overload increased LV mass by approximately 40% in both standard and high-fat diets without fish oil. Supplementation with fish oil increased their incorporation into cardiac phospholipids, and decreased the proinflammatory fatty acid arachidonic acid and urine thromboxane B(2) with both the standard and high-fat diet. Linoleic acid and tetralinoloyl cardiolipin (an essential mitochondrial phospholipid) were decreased with pressure overload on standard diet, which was prevented by fish oil. Animals fed high-fat diet had decreased linoleic acid and tetralinoloyl cardiolipin regardless of fish oil supplementation. Fish oil limited LV hypertrophy on the standard diet, and prevented upregulation of fetal genes associated with heart failure (myosin heavy chain-beta and atrial natriuetic factor). These beneficial effects of fish oil were absent in animals on the high-fat diet. In conclusion, whereas treatment with EPA+DHA prevented tetralinoloyl cardiolipin depletion, LV hypertrophy, and abnormal genes expression with pressure overload, these effects were absent with a high-fat diet.

  17. Acute molecular mechanisms responsive to feeding and meal constitution in mesenteric adipose tissue.

    PubMed

    Bolduc, Carl; Yoshioka, Mayumi; St-Amand, Jonny

    2010-02-01

    To identify the acute effects of feeding on mesenteric fat, we have performed a transcriptomic study in the mesenteric adipose tissue after low-fat (LF) and high-fat (HF) meal ingestion. After fasting, one group of mice was killed and the others were fed ad libitum with HF or LF meal, and killed 3 h after the ingestion. Serial analysis of gene expression (SAGE) was performed, generating approximately 150,000 tags/sample. The results were confirmed using quantitative real-time PCR (qRT-PCR). Transcripts involved in lipid biosynthesis were upregulated only by LF meal, whereas intracellular lipid catabolism was repressed by feeding. Apoptotic genes were downregulated, whereas antiapoptosis and proteolysis were upregulated by feeding. The expression levels of genes coding for adiponectin and ribosomal proteins were decreased by HF meal, as well as transcripts involved in mRNA processing, cytoskeleton, and extracellular matrix. Several other fat-responsive genes were identified, including diverse uncharacterized transcripts. These results revealed that mesenteric adipose tissue transcriptome was responsive to food intake and was affected differently according to meal constitution. The identification of uncharacterized transcripts regulated by LF and HF meals is a first step toward further understanding the early mechanisms of diet-induced obesity as well as discovering new therapeutic targets for obesity-related diseases.

  18. Meals Served in Public Schools.

    ERIC Educational Resources Information Center

    Vivigal, Lisa

    The Physicians Committee for Responsible Medicine (PCRM) contacted public school districts around the United States to determine if they offered low-fat, healthful meals. The PCRM ranked the schools according to whether they served low-fat and vegetarian meals daily, whether these meals varied through the week, and whether children needed to…

  19. Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model

    PubMed Central

    Fabbrini, Elisa; Higgins, Paul B.; Magkos, Faidon; Bastarrachea, Raul A.; Voruganti, V. Saroja; Comuzzie, Anthony G.; Shade, Robert E.; Gastaldelli, Amalia; Horton, Jay D.; Omodei, Daniela; Patterson, Bruce W.

    2013-01-01

    We established a model of chronic portal vein catheterization in an awake nonhuman primate to provide a comprehensive evaluation of the metabolic response to low-carbohydrate/high-fat (LCHF; 20% carbohydrate and 65% fat) and high-carbohydrate/low-fat (HCLF; 65% carbohydrate and 20% fat) meal ingestion. Each meal was given 1 wk apart to five young adult (7.8 ± 1.3 yr old) male baboons. A [U-13C]glucose tracer was added to the meal, and a [6,6-2H2]glucose tracer was infused systemically to assess glucose kinetics. Plasma areas under the curve (AUCs) of glucose, insulin, and C-peptide in the femoral artery and of glucose and insulin in the portal vein were higher (P ≤ 0.05) after ingestion of the HCLF compared with the LCHF meal. Compared with the LCHF meal, the rate of appearance of ingested glucose into the portal vein and the systemic circulation was greater after the HCLF meal (P < 0.05). Endogenous glucose production decreased by ∼40% after ingestion of the HCLF meal but was not affected by the LCHF meal (P < 0.05). Portal vein blood flow increased (P < 0.001) to a similar extent after consumption of either meal. In conclusion, a LCHF diet causes minimal changes in the rate of glucose appearance in both portal and systemic circulations, does not affect the rate of endogenous glucose production, and causes minimal stimulation of C-peptide and insulin. These observations demonstrate that LCHF diets cause minimal perturbations in glucose homeostasis and pancreatic β-cell activity. PMID:23269412

  20. Oxyresveratrol Supplementation to C57bl/6 Mice Fed with a High-Fat Diet Ameliorates Obesity-Associated Symptoms

    PubMed Central

    Tan, Hui Yuan; Tse, Iris Mei Ying; Li, Edmund Tsze Shing; Wang, Mingfu

    2017-01-01

    Oxyresveratrol has been proven effective in inhibiting adipogenesis in a 3T3-L1 cell model. We investigated the preventive effect of oxyresveratrol supplementation on obesity development in high-fat diet-fed mice. Male C57bl/6 mice were randomly subjected to control (5% fat by weight, LF), high-fat (30% fat by weight, HF), and high-fat supplemented with 0.25% and 0.5% oxyresveratrol (OXY1 and OXY2, respectively) diet groups for eight weeks. Oxyresveratrol supplementation effectively alleviated obesity-associated symptoms such as insulin resistance, hyperglycemia, and hepatic steatosis in high-fat diet-fed mice. Compared to the high-fat diet group, oxyresveratrol supplementation suppressed expression of glucose-6-phosphatase, sterol regulatory element-binding proteins 1, fatty acid synthase and CCAAT/Enhancer-binding proteins α, and elevated AMP-activated protein kinase (α2-catalytic subunit) level in liver, upregulated insulin-dependent glucose transporter type 4 level in adipose tissue, and increased expression of insulin receptor substrate 1, insulin-dependent glucose transporter type 4, AMP-activated protein kinase α, peroxisome proliferator-activated receptor γ coactivator-1α, and sirtuin 1 in muscle to regulate lipid and glucose homeostasis in these tissues. This study demonstrated that oxyresveratrol supplementation effectively ameliorated obesity-associated symptoms in high-fat diet-fed mice, presumably attributed to mediating critical regulators involved in lipid and glucose homeostasis in liver, visceral fat, and muscle. PMID:28212343

  1. Effects of pectin lyase-modified red ginseng extracts in high-fat diet-fed obese mice

    PubMed Central

    Lee, Hak-Yong; Park, Kwang-Hyun; Park, Young-Mi; Moon, Dae-In; Oh, Hong-Geun; Kwon, Dae-Young; Yang, Hye-Jeong; Kim, Okjin; Kim, Dong-Woo; Yoo, Ji-Hyun; Hong, Se-Chul; Lee, Kun-Hee; Seol, Su-Yeon; Park, Yong-Sik; Park, Jong-Dae

    2014-01-01

    Red ginseng and its extracts have been used as traditional medicines and functional foods in countries worldwide. The aim of this study was to examine the bioavailability of pectin lyase-modified red ginseng extracts (GS-E3D), and the effects of GS-E3D on adipogenesis of 3T3-L1 adipocytes, as well as on metabolic disorders such as hyperglycemia, dyslipidemia, and fatty liver in high-fat diet fed obese C57BL/6 mice. Mice were divided into 5 groups: normal diet group, high fat diet-vehicle group, high fat diet + 0.1 g/kg GS-E3D (0.1-GS-E3D), high fat diet + 0.3 g/kg (0.3-GS-E3D), high fat diet + 1.0 g/kg (1.0-GS-E3D). Treatment of GS-E3D reduced differentiation of 3T3-L1 adipocytes with low cytotoxicity. In the animal model, compared to the high fat diet control, serum glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TG, and leptin level were reduced in treatment animals in a dose-dependent manner. In addition, we found that GS-E3D could decrease total hepatic lipid droplets. These results suggest that GS-E3D, as a dietary supplement, has beneficial effects on obesity and may have useful effects in health-care products. PMID:25628725

  2. Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

    PubMed Central

    Bravo, Elena; Palleschi, Simonetta; Rossi, Barbara; Napolitano, Mariarosaria; Tiano, Luca; D’Amore, Emanuela; Botham, Kathleen M

    2012-01-01

    Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress. PMID:22408414

  3. Antihyperglycemic and antioxidative effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in mice fed with a high fat diet.

    PubMed

    Ban, Su Jeong; Rico, Catherine W; Um, In Chul; Kang, Mi Young

    2012-01-01

    The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress.

  4. Antihyperglycemic and Antioxidative Effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in Mice Fed with a High Fat Diet

    PubMed Central

    Ban, Su Jeong; Rico, Catherine W.; Um, In Chul; Kang, Mi Young

    2012-01-01

    The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress. PMID:22489179

  5. Oxyresveratrol Supplementation to C57bl/6 Mice Fed with a High-Fat Diet Ameliorates Obesity-Associated Symptoms.

    PubMed

    Tan, Hui Yuan; Tse, Iris Mei Ying; Li, Edmund Tsze Shing; Wang, Mingfu

    2017-02-16

    Oxyresveratrol has been proven effective in inhibiting adipogenesis in a 3T3-L1 cell model. We investigated the preventive effect of oxyresveratrol supplementation on obesity development in high-fat diet-fed mice. Male C57bl/6 mice were randomly subjected to control (5% fat by weight, LF), high-fat (30% fat by weight, HF), and high-fat supplemented with 0.25% and 0.5% oxyresveratrol (OXY1 and OXY2, respectively) diet groups for eight weeks. Oxyresveratrol supplementation effectively alleviated obesity-associated symptoms such as insulin resistance, hyperglycemia, and hepatic steatosis in high-fat diet-fed mice. Compared to the high-fat diet group, oxyresveratrol supplementation suppressed expression of glucose-6-phosphatase, sterol regulatory element-binding proteins 1, fatty acid synthase and CCAAT/Enhancer-binding proteins α, and elevated AMP-activated protein kinase (α2-catalytic subunit) level in liver, upregulated insulin-dependent glucose transporter type 4 level in adipose tissue, and increased expression of insulin receptor substrate 1, insulin-dependent glucose transporter type 4, AMP-activated protein kinase α, peroxisome proliferator-activated receptor γ coactivator-1α, and sirtuin 1 in muscle to regulate lipid and glucose homeostasis in these tissues. This study demonstrated that oxyresveratrol supplementation effectively ameliorated obesity-associated symptoms in high-fat diet-fed mice, presumably attributed to mediating critical regulators involved in lipid and glucose homeostasis in liver, visceral fat, and muscle.

  6. Changes in the small intestine of Schistosoma mansoni-infected mice fed a high-fat diet.

    PubMed

    Alencar, Alba Cristina Miranda de Barros; Neves, Renata Heisler; de Oliveira, Albanita Viana; Machado-Silva, José Roberto

    2012-05-01

    The consumption of a high-fat diet modifies both the morphology of the small intestine and experimentally tested effects of schistosomiasis mansoni. However, whether a schistosomiasis infection associated with a high-fat diet causes injury to the small intestine has never been investigated. Mice were fed either a high-fat or a standard-fat diet for 6 months and were then infected with Schistosoma mansoni cercariae. Physical characteristics of the intestinal tissue (mucosal thickness, small intestinal villi length and height, and abundance of goblet cells and enterocytes on the villous surface) and the distribution of granulomas along the intestinal segments and their developmental stage were measured at the time of sacrifice (9 or 17 weeks post-infection). The group fed a high-fat diet exhibited different granuloma stages, whereas the control group possessed only exudative granulomas. The chronically infected mice fed a high-fat diet exhibited higher granuloma and egg numbers than the acutely infected group. Exudative, exudative/exudative-productive and exudative-productive granulomas were present irrespective of diet. Computer-aided morphometric analysis confirmed that villus length, villus width, muscular height and submucosal height of the duodenal and jejunal segments were affected by diet and infection. In conclusion, a high-fat diet and infection had a significant impact on the small intestine morphology and morphometry among the animals tested.

  7. Districts Tackling Meal Debt

    ERIC Educational Resources Information Center

    Shah, Nirvi

    2012-01-01

    School districts have resorted to hiring debt collectors, employing constables, and swapping out standard meals for scaled-back versions to try to coerce parents to pay off school lunch debt that, in recent years, appears to have surged as the result of a faltering economy and better record-keeping. While the average school lunch costs just about…

  8. Meals in nursing homes.

    PubMed

    Kofod, Jens; Birkemose, Anna

    2004-06-01

    Undernutrition is present among 33% of nursing home residents in Denmark. Hence, it is relevant to examine the meal situation at nursing homes to single out factors that may increase or reduce the residents' food intake. In the ongoing Danish nursing home debate it is claimed that a new type of nursing home improves the residents' meal situation with a positive effect on nutrition. The aim of this work is to test the general hypothesis that (i) residents appreciate the meal situation in these nursing homes and (ii) nutritional status of the residents is improved in this type of nursing home. This study was carried out in four Danish nursing homes at various locations in Denmark. The methods used are qualitative interviews and observations at four nursing homes in combination with measurement of body mass index (BMI) at two of the four nursing homes. Undernutrition is defined as a BMI below 20. The study could not confirm the general hypothesis, as a consistent improvement in the meal situation was not found in the nursing homes studied. But an indication of improved nutritional status was found in two of the nursing homes where the degree of undernutrition was lower than generally found in Denmark. Furthermore, the study indicated that the staff and the residents conceived the nursing homes differently.

  9. Impact of high-fat diet and obesity on energy balance and fuel utilization during the metabolic challenge of lactation.

    PubMed

    Wahlig, Jessica L; Bales, Elise S; Jackman, Matthew R; Johnson, Ginger C; McManaman, James L; Maclean, Paul S

    2012-01-01

    The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific metabolism of lactating dams and their offspring were examined in C57/B6 mice. Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln, and HF-Ob dams exhibited a greater positive energy balance (EB) and increased dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De novo synthesized fat was decreased in tissues and milk from HF-fed dams compared to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was associated with reduced milk triglycerides relative to lean controls (P < 0.05). Compared to HF diet alone obesity has additional adverse affects, impairing both lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these data show that consumption of a HF diet significantly affects maternal and neonatal metabolism and that maternal obesity can independently alter these responses.

  10. Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high fat diet and ovariectomy in mice.

    PubMed

    Ohtake, Kazuo; Ehara, Nobuyuki; Chiba, Hiroshige; Nakano, Genya; Sonoda, Kunihiro; Ito, Junta; Uchida, Hiroyuki; Kobayashi, Jun

    2017-02-14

    Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect in this syndrome. We examined the effect of dietary nitrite on mice model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) with high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF without or with sodium nitrite (50mg and 150mg/L) in drinking water. Daily food intake and weekly body weight were monitored for 18 weeks. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and developed obesity with visceral hypertrophic adipocytes, and increased transcriptional levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrotizing factor-α (TNF-α) and interleukin-6 (IL-6) in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that endogenous NO defect might underlie postmenopausal metabolic syndrome, and dietary nitrite provides an alternative source of NO, and subsequently compensating for metabolic impairments of this syndrome.

  11. Impact of High-Fat Diet and Obesity on Energy Balance and Fuel Utilization During the Metabolic Challenge of Lactation

    PubMed Central

    Wahlig, Jessica L.; Bales, Elise S.; Jackman, Matthew R.; Johnson, Ginger C.; McManaman, James L.; MacLean, Paul S.

    2014-01-01

    The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific metabolism of lactating dams and their offspring were examined in C57/B6 mice. Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln, and HF-Ob dams exhibited a greater positive energy balance (EB) and increased dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De novo synthesized fat was decreased in tissues and milk from HF-fed dams compared to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was associated with reduced milk triglycerides relative to lean controls (P < 0.05). Compared to HF diet alone obesity has additional adverse affects, impairing both lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these data show that consumption of a HF diet significantly affects maternal and neonatal metabolism and that maternal obesity can independently alter these responses. PMID:21720435

  12. Deletion of miR-150 Exacerbates Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic Mice.

    PubMed

    Shi, Liheng; Kim, Andy Jeesu; Chang, Richard Cheng-An; Chang, Janet Ya-An; Ying, Wei; Ko, Michael L; Zhou, Beiyan; Ko, Gladys Yi-Ping

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness among American adults above 40 years old. The vascular complication in DR is a major cause of visual impairment, making finding therapeutic targets to block pathological angiogenesis a primary goal for developing DR treatments. MicroRNAs (miRs) have been proposed as diagnostic biomarkers and potential therapeutic targets for various ocular diseases including DR. In diabetic animals, the expression levels of several miRs, including miR-150, are altered. The expression of miR-150 is significantly suppressed in pathological neovascularization in mice with hyperoxia-induced retinopathy. The purpose of this study was to investigate the functional role of miR-150 in the development of retinal microvasculature complications in high-fat-diet (HFD) induced type 2 diabetic mice. Wild type (WT) and miR-150 null mutant (miR-150-/-) male mice were given a HFD (59% fat calories) or normal chow diet. Chronic HFD caused a decrease of serum miR-150 in WT mice. Mice on HFD for 7 months (both WT and miR-150-/-) had significant decreases in retinal light responses measured by electroretinograms (ERGs). The retinal neovascularization in miR-150-/--HFD mice was significantly higher compared to their age matched WT-HFD mice, which indicates that miR-150 null mutation exacerbates chronic HFD-induced neovascularization in the retina. Overexpression of miR-150 in cultured endothelial cells caused a significant reduction of vascular endothelial growth factor receptor 2 (VEGFR2) protein levels. Hence, deletion of miR-150 significantly increased the retinal pathological angiogenesis in HFD induced type 2 diabetic mice, which was in part through VEGFR2.

  13. Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content.

    PubMed

    Shapiro, Alexandra; Tümer, Nihal; Gao, Yongxin; Cheng, Kit-Yan; Scarpace, Philip J

    2011-08-01

    Chronic consumption of a Western-type diet, containing both elevated sugar and fat, results in leptin resistance. We hypothesised that fructose, as part of the sugar component of Western-type diets, is one causative ingredient in the development of leptin resistance and that removal of this component will prevent leptin resistance despite high fat (HF) content. We fed rats a sugar-free (SF), 30 % HF (SF/HF) diet or a 40 % high-fructose (HFr), 30 % HF (HFr/HF) diet for 134 d. The HFr/HF diet resulted in impaired anorexic and body-weight responses to both peripherally (0·6 mg/kg, assessed on day 65 of the diet) and centrally (1·5 μg/d, assessed on days 129-134) administered leptin, whereas SF/HF-fed rats were fully leptin responsive. At day 70, half the HFr/HF-fed animals were switched to the SF/HF diet, reversing the leptin resistance (assessed 18 d after the diet switch). The HFr/HF diet elevated serum leptin and reduced adiponectin, and levels were restored abruptly at day 3 after switching to the SF/HF diet. These data demonstrate that a diet containing both HFr and fat leads to leptin resistance, while an isoenergetic SF/HF diet does not. Moreover, removal of fructose from this diet reverses the leptin resistance and the elevated leptin, suggesting a cause-and-effect relationship. These data suggest that fructose is the bioactive component of a HF/high-sugar diet that is essential for the induction of leptin resistance.

  14. Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice

    PubMed Central

    Spruiell, Krisstonia; Jones, Dominique Z.; Cullen, John M.; Awumey, Emmanuel M.; Gonzalez, Frank J.; Gyamfi, Maxwell A.

    2014-01-01

    Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized (“postmenopausal”) females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor α (ERα) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17β-estradiol levels, and WAT ERα expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women. PMID:24721462

  15. Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.

    PubMed

    Hwang, Ling-Ling; Wang, Chien-Hua; Li, Tzu-Ling; Chang, Shih-Dar; Lin, Li-Chun; Chen, Ching-Ping; Chen, Chiung-Tong; Liang, Keng-Chen; Ho, Ing-Kang; Yang, Wei-Shiung; Chiou, Lih-Chu

    2010-03-01

    Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.

  16. Biocompounds Attenuating the Development of Obesity and Insulin Resistance Produced by a High-fat Sucrose Diet.

    PubMed

    Etxeberria, Usune; de la Garza, Ana Laura; Martíinez, J Alfredo; Milagro, I

    2015-08-01

    The use of biocompounds as agents with potential anti-obesity effects might be a feasible alternative to the prescription of traditional drugs in the near future. The goal of the present study was to screen five different compounds in relation to their ability to prevent body weight gain and ameliorate obesity-associated metabolic impairments, namely insulin resistance. For this purpose, seventy Wistar rats were randomly assigned into seven experimental groups. A standard diet-fed control group (control, n=10); a high-fat, high-sucrose diet-fed group (HFS, n=10) and five experimental groups which were fed the HFS diet supplemented with one of the following biocompounds; curcumin (100 mg/kg bw, n=10), chlorogenic acid (50 mg/kg bw, n=10), coumaric acid (100 mg/kg bw, n=10), naringin (100 mg/kg bw, n=10) and leucine (1% of diet, n=10). These results confirm the effectiveness of all the compounds to reduce significantly food efficiency, despite the significant higher food intake. Moreover, visceral fat mass percentage was significantly decreased after naringin and coumaric acid supplementation. In fact, this finding might be related to the considerable amelioration of HOMA-IR index detected in naringin-treated animals. A significant reduction in serum insulin levels and an improvement in the intraperitoneal glucose tolerance test and AUC were found in leucine- and coumaric acid-treated rats, respectively. In summary, the tested biocompounds, particularly naringin, coumaric acid and leucine, showed potential benefits in the prevention of obesity-related complications in rats, at least at the proved doses.

  17. Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats.

    PubMed

    Poudyal, Hemant; Campbell, Fiona; Brown, Lindsay

    2010-05-01

    Olive oil, an important component of the Mediterranean diet, produces cardioprotective effects, probably due to both oleic acid and the polyphenols such as oleuropein and hydroxytyrosol. Our aim in this study was to assess whether a polyphenol-enriched extract from the leaves of Olea europaea L. with oleuropein as the major component attenuated the cardiovascular, hepatic, and metabolic signs of a high-carbohydrate, high-fat (HCHF) diet (carbohydrate, 52%; fat, 24%, 25% fructose in drinking water) in rats. Male Wistar rats were fed either a cornstarch diet (CS) or a HCHF diet for a total of 16 wk. Diets of the treatment groups [CS+olive leaf extract (OLE) and HCHF+OLE] were supplemented with 3% OLE after 8 wk of being fed their respective CS or HCHF diets for a further 8 wk. After 16 wk, HCHF rats developed signs of metabolic syndrome, including elevated abdominal and hepatic fat deposition, collagen deposition in heart and liver, cardiac stiffness, and oxidative stress markers (plasma malondialdehyde and uric acid concentrations), with diminished aortic ring reactivity, abnormal plasma lipid profile, impaired glucose tolerance, and hypertension. Compared with HCHF rats, those in the HCHF+OLE group had improved or normalized cardiovascular, hepatic, and metabolic signs with the exception of elevated blood pressure. These results strongly suggest that an OLE containing polyphenols such as oleuropein and hydroxytyrosol reverses the chronic inflammation and oxidative stress that induces the cardiovascular, hepatic, and metabolic symptoms in this rat model of diet-induced obesity and diabetes without changing blood pressure.

  18. Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice

    PubMed Central

    Heyman-Lindén, Lovisa; Kotowska, Dorota; Sand, Elin; Bjursell, Mikael; Plaza, Merichel; Turner, Charlotta; Holm, Cecilia; Fåk, Frida; Berger, Karin

    2016-01-01

    Background The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. Conclusions Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain. PMID:27125264

  19. Chronic mild stress induces variations in locomotive behavior and metabolic rates in high fat fed rats.

    PubMed

    García-Díaz, D F; Campion, J; Milagro, F I; Lomba, A; Marzo, F; Martínez, J A

    2007-12-01

    Chronic mild stress (CMS) has been often associated to the pathogenesis of many diseases including obesity. Indeed, visceral obesity has been linked to the development of metabolic syndrome features and constitutes a serious risk factor for cardiovascular diseases and diabetes. In order to study possible mechanistic relationships between stress and the onset of obesity, we developed during 11 weeks a model of high-fat dietary intake (cafeteria diet) together with a CMS regimen in male Wistar rats. During the experimental period, basal metabolism by indirect calorimetry, rectal temperature, food intake, and locomotive markers were specifically analyzed. After 77 days, animals were sacrificed and body, adiposity and plasma biochemical profiles were also examined. As expected, cafeteria diet in unstressed animals induced a significative increase in body weight, adiposity, and insulin resistance markers. Locomotive variables, specifically distance, rearing and meander, were significantly increased by CMS on the first weeks of stress. Moreover, this model of CMS in Wistar rats increased significantly energy expenditure, and apparently interplayed with the dietary treatment on the muscle weight/fat weight ratio. In summary, this chronic stress model did not affected weight gain in control and high fat fed animals, but induced an interaction concerning the metabolic muscle/fat repartitioning.

  20. Bardoxolone Methyl Prevents Mesenteric Fat Deposition and Inflammation in High-Fat Diet Mice

    PubMed Central

    Dinh, Chi H. L.; Szabo, Alexander; Yu, Yinghua; Camer, Danielle; Wang, Hongqin; Huang, Xu-Feng

    2015-01-01

    Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue. PMID:26618193

  1. Chemotherapy can induce weight normalization of morbidly obese mice despite undiminished ingestion of high fat diet.

    PubMed

    Myers, Cheryl E; Hoelzinger, Dominique B; Truong, Tiffany N; Chew, Lindsey A; Myles, Arpita; Chaudhuri, Leena; Egan, Jan B; Liu, Jun; Gendler, Sandra J; Cohen, Peter A

    2017-01-17

    Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD. Weight reduction was not attributable to decreased HFD intake, enhanced energy expenditure or malabsorption. MTX or CY dosing significantly depleted both adipose tissue and preadipocyte progenitors. Remarkably, however, despite continued high fat feeding, a compensatory increase in hepatocyte lipid storage was not observed, but rather the opposite. Gene microarray liver analyses demonstrated that HFD mice receiving MTX or CY experienced significantly inhibited lipogenesis and lipid storage, whereas Enho (energy homeostasis) gene expression was significantly upregulated. Further metabolic studies employing a human hepatocellular line revealed that MTX treatment preserved robust oxidative phosphorylation, but also promoted mitochondrial uncoupling with a surge in proton leak. This is the first report that certain optimally dosed chemotherapeutic agents can induce weight loss in morbidly obese mice without reduced dietary intake, apparently by depleting stores of adipocytes and their progenitors, curtailment of lipogenesis, and inconspicuous disposal of incoming dietary lipid via a steady state partial uncoupling of mitochondrial oxidative phosphorylation.

  2. Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet.

    PubMed

    Nizari, Shereen; Carare, Roxana O; Hawkes, Cheryl A

    2016-02-25

    Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD.

  3. A high-fat, ketogenic diet induces a unique metabolic state in mice.

    PubMed

    Kennedy, Adam R; Pissios, Pavlos; Otu, Hasan; Roberson, Russell; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E; Liu, Fen-Fen; Kahn, Barbara B; Libermann, Towia A; Maratos-Flier, Eleftheria

    2007-06-01

    Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

  4. Lipid and fatty acid profiles in rats consuming different high-fat ketogenic diets.

    PubMed

    Dell, C A; Likhodii, S S; Musa, K; Ryan, M A; Burnham, W M; Cunnane, S C

    2001-04-01

    High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which these diets work or whether fats rich in n-3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride, flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of alpha-linolenate in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid profiles can confer a similar amount of seizure protection.

  5. Triticale Bran Alkylresorcinols Enhance Resistance to Oxidative Stress in Mice Fed a High-Fat Diet

    PubMed Central

    Agil, Rania; Patterson, Zachary R.; Mackay, Harry; Abizaid, Alfonso; Hosseinian, Farah

    2016-01-01

    Triticale (× Triticosecale Whitm.) is a cereal grain with high levels of alkyresorcinols (AR) concentrated in the bran. These phenolic lipids have been shown to reduce or inhibit triglyceride accumulation and protect against oxidation; however, their biological effects have yet to be evaluated in vivo. The purpose of this study was to determine the effects of ARs extracted from triticale bran (TB) added to a high–fat diet on the development of obesity and oxidative stress. CF-1 mice were fed a standard low-fat (LF) diet, a 60% high-fat diet (HF) and HF diets containing either 0.5% AR extract (HF-AR), 10% TB (HF-TB), or 0.5% vitamin E (HF-VE). Energy intake, weight gain, glucose tolerance, fasting blood glucose (FBG) levels, and body composition were determined. Oxygen radical absorbance capacity (ORAC), superoxide dismutase (SOD) activity, and glutathione (GSH) assays were performed on mice liver and heart tissues. The findings suggest that ARs may serve as a preventative measure against risks of oxidative damage associated with high-fat diets and obesity through their application as functional foods and neutraceuticals. Future studies aim to identify the in vivo mechanisms of action of ARs and the individual homologs involved in their favorable biological effects. PMID:28231100

  6. Anti-obesity effect of alkaline reduced water in high fat-fed obese mice.

    PubMed

    Ignacio, Rosa Mistica Coles; Kang, Tae-Young; Kim, Cheol-Su; Kim, Soo-Ki; Yang, Young-Chul; Sohn, Joon-Hyung; Lee, Kyu-Jae

    2013-01-01

    Whether or not alkaline reduced water (ARW) has a positive effect on obesity is unclear. This study aims to prove the positive effect of ARW in high-fat (HF) diet-induced obesity (DIO) in C57BL/6 mice model. Toward this, obesity was induced by feeding the C57BL/6 male mice with high-fat diet (w/w 45% fat) for 12 weeks. Thereafter, the animals were administered with either ARW or tap water. Next, the degree of adiposity and DIO-associated parameters were assessed: clinico-pathological parameters, biochemical measurements, histopathological analysis of liver, the expression of cholesterol metabolism-related genes in the liver, and serum levels of adipokine and cytokine. We found that ARW-fed mice significantly ameliorated adiposity: controlled body weight gain, reduced the accumulation of epididymal fats and decreased liver fats as compared to control mice. Accordingly, ARW coordinated the level of adiponectin and leptin. Further, mRNA expression of cytochrome P450 (CYP)7A1 was upregulated. In summary, our data shows that ARW intake inhibits the progression of HF-DIO in mice. This is the first note on anti-obesity effect of ARW, clinically implying the safer fluid remedy for obesity control.

  7. A high-fat diet regulates gastrin and acid secretion through primary cilia.

    PubMed

    Saqui-Salces, Milena; Dowdle, William E; Reiter, Jeremy F; Merchant, Juanita L

    2012-08-01

    The role of primary cilia in the gastrointestinal tract has not been examined. Here we report the presence of primary cilia on gastric endocrine cells producing gastrin, ghrelin, and somatostatin (Sst), hormones regulated by food intake. During eating, cilia in the gastric antrum decreased, whereas gastric acid and circulating gastrin increased. Mice fed high-fat chow showed a delayed decrease in antral cilia, increased plasma gastrin, and gastric acidity. Mice fed high-fat chow for 3 wk showed lower cilia numbers and acid but higher gastrin levels than mice fed a standard diet, suggesting that fat affects gastric physiology. Ex vivo experiments showed that cilia in the corpus responded to acid and distension, whereas cilia in the antrum responded to food. To analyze the role of gastric cilia, we conditionally deleted the intraflagellar transport protein Ift88 (Ift88(-/fl)). In fed Ift88(-/fl) mice, gastrin levels were higher, and gastric acidity was lower. Moreover, gastrin and Sst gene expression did not change in response to food as in controls. At 8 mo, Ift88(-/fl) mice developed foveolar hyperplasia, hypergastrinemia, and hypochlorhydria associated with endocrine dysfunction. Our results show that components of food (fat) are sensed by antral cilia on endocrine cells, which modulates gastrin secretion and gastric acidity.

  8. Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model

    PubMed Central

    Harris, R. Alan; Alcott, Callison E.; Sullivan, Elinor L.; Takahashi, Diana; McCurdy, Carrie E.; Comstock, Sarah; Baquero, Karalee; Blundell, Peter; Frias, Antonio E.; Kahr, Maike; Suter, Melissa; Wesolowski, Stephanie; Friedman, Jacob E.; Grove, Kevin L.; Aagaard, Kjersti M.

    2016-01-01

    Maternal obesity contributes to an increased risk of lifelong morbidity and mortality for both the mother and her offspring. In order to better understand the molecular mechanisms underlying these risks, we previously established and extensively characterized a primate model in Macaca fuscata (Japanese macaque). In prior studies we have demonstrated that a high fat, caloric dense maternal diet structures the offspring’s epigenome, metabolome, and intestinal microbiome. During the course of this work we have consistently observed that a 36% fat diet leads to obesity in the majority, but not all, of exposed dams. In the current study, we sought to identify the genomic loci rendering resistance to obesity despite chronic consumption of a high fat diet in macaque dams. Through extensive phenotyping together with exon capture array and targeted resequencing, we identified three novel single nucleotide polymorphisms (SNPs), two in apolipoprotein B (APOB) and one in phospholipase A2 (PLA2G4A) that significantly associated with persistent weight stability and insulin sensitivity in lean macaques. By application of explicit orthogonal modeling (NOIA), we estimated the polygenic and interactive nature of these loci against multiple metabolic traits and their measures (i.e., serum LDL levels) which collectively render an obesity resistant phenotype in our adult female dams. PMID:27811965

  9. Antihyperlipidemic effects of Sesamum indicum L. in rabbits fed a high-fat diet.

    PubMed

    Asgary, Sedigheh; Rafieian-Kopaei, Mahmoud; Najafi, Somayeh; Heidarian, Esfandiar; Sahebkar, Amirhossein

    2013-01-01

    The present study aimed to investigate the anti-hyperlipidemic effects of sesame in a high-fat fed rabbit model. Animals were randomly divided into four groups of eight animals each for 60 days as follows: normal diet, hypercholesterolemic diet (1% cholesterol), hypercholesterolemic diet (1% cholesterol) + sesame seed (10%), and hypercholesterolemic diet (1% cholesterol) + sesame oil (5%). Serum concentrations of total cholesterol, LDL-C, HDL-C, triglycerides, apoA and apoB, SGOT, SGPT, glucose and insulin were measured at the end of supplementation period in all studied groups. Hypercholesterolemic feeding resulted in a significant elevation of TC, TG, LDL-C, HDL-C, SGOT and SGPT as compared to the normocholesterolemic diet group (P < 0.05). Supplementation with sesame seed did not cause any significant alteration in lipid profile parameters, apolipoproteins, hepatic transaminases, glucose and insulin as compared to the hypercholesterolemic diet group (P > 0.05). In contrast, rabbits supplemented with sesame oil were found to have lower circulating concentrations of TC, LDL-C, HDL-C, SGOT and SGPT (P < 0.05), whilst concentrations of TG, apoA, apoB, insulin and glucose remained unaltered compared to the hypercholesterolemic diet group (P > 0.05). Supplementation with sesame oil, but not sesame seed, can ameliorate serum levels of lipids and hepatic enzymes in rabbits under a high-fat diet.

  10. Lipoprotein lipase activity and chylomicron clearance in rats fed a high fat diet

    SciTech Connect

    Brown, C.M.; Layman, D.K.

    1988-11-01

    The relationships of tissue and plasma lipoprotein lipase (LPL) activities to tissue uptake and plasma clearance of UC-labeled chylomicron-triglyceride ( UC-CM-TG) were studied in female rats fed isoenergetic and isonitrogenous control (12% kJ from fat) or high fat diets (72% kJ from fat) for 8 wk. Animals fed the high-fat diet had higher levels of fasting plasma triglycerides and lower LPL activities in heart, renal adipose tissue and post-heparin plasma. Changes in LPL activities of skeletal muscles varied among muscles with higher values in the soleus and plantaris (32-61%) and no differences in the gastrocnemius. The lower LPL activity in renal adipose tissue was associated with lower uptake of fatty acids from UC-CM-TG by adipose. Fatty-acid uptake from labeled TG was not associated with tissue LPL activity in other tissues. Clearance of UC-CM-TG from plasma and the half-lives of UC-CM-TG were similar in both dietary groups. These data indicate that tissue and plasma LPL activities are not a direct index of uptake of fatty acids by tissues or clearance of chylomicron triglycerides.

  11. Taurine Treatment Modulates Circadian Rhythms in Mice Fed A High Fat Diet

    PubMed Central

    Figueroa, Ana Lucia C.; Figueiredo, Hugo; Rebuffat, Sandra A.; Vieira, Elaine; Gomis, Ramon

    2016-01-01

    Close ties have been made among certain nutrients, obesity, type 2 diabetes and circadian clocks. Among nutrients, taurine has been documented as being effective against obesity and type 2 diabetes. However, the impact of taurine on circadian clocks has not been elucidated. We investigated whether taurine can modulate or correct disturbances in daily rhythms caused by a high-fat diet in mice. Male C57BL/6 mice were divided in four groups: control (C), control + taurine (C+T), high-fat diet (HFD) and HFD + taurine (HFD+T). They were administered 2% taurine in their drinking water for 10 weeks. Mice were euthanized at 6:00, 12:00, 18:00, and 24:00. HFD mice increased body weight, visceral fat and food intake, as well as higher levels of glucose, insulin and leptin, throughout the 24 h. Taurine prevented increments in food intake, body weight and visceral fat, improved glucose tolerance and insulin sensitivity and reduced disturbances in the 24 h patterns of plasma insulin and leptin. HFD downregulated the expression of clock genes Rev-erbα, Bmal1, and Per1 in pancreatic islets. Taurine normalized the gene and protein expression of PER1 in beta-cells, which suggests that it could be beneficial for the correction of daily rhythms and the amelioration of obesity and diabetes. PMID:27857215

  12. MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

    PubMed Central

    Moore, C. E. J.; Pickford, J.; Cagampang, F. R.; Stead, R. L.; Tian, S.; Zhao, X.; Tang, X.; Byrne, C. D.; Proud, C. G.

    2016-01-01

    The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease. PMID:27087055

  13. Metformin improves metabolic memory in high fat diet (HFD)-induced renal dysfunction.

    PubMed

    Tikoo, Kulbhushan; Sharma, Ekta; Amara, Venkateswara Rao; Pamulapati, Himani; Dhawale, Vaibhav Shrirang

    2016-08-22

    Recently, we have shown that high fat diet (HFD) in vivo and in vitro generates metabolic memory by altering H3K36me2 and H3K27me3 on the promoter of FOXO1 (transcription factor of gluconeogenic genes) (Kumar et al., 2015). Here we checked the hypothesis, whether concomitant diet reversal and metformin could overcome HFD-induced metabolic memory and renal damage. Male adult Sprague Dawley rats were rendered insulin resistant by feeding high fat diet for 16 weeks. Then the rats were subjected to diet reversal (REV) alone and along with metformin (REV+MET) for 8 weeks. Biochemical and histological markers of insulin resistance and kidney function were measured. Blood pressure and in vivo vascular reactivity to Angiotensin II (200 mgkg-1) were also checked. Diet reversal could improve lipid profile but could not prevent renal complications induced by HFD. Interestingly, metformin along with diet reversal restored the levels of blood glucose, triglycerides, cholesterol, blood urea nitrogen and creatinine. In kidney, metformin increased the activation of AMPK, decreased inflammatory markers-COX-2, IL-1β and apoptotic markers-PARP, Caspase3. Metformin was effective in lowering the elevated basal blood pressure, acute change in mean arterial pressure (ΔMAP) in response to Ang II. It also attenuated the tubulointerstitial fibrosis and glomerulosclerosis induced by HFD-feeding in kidney. Here we report for the first time, that metformin treatment overcomes metabolic memory and prevents HFD-induced renal damage.

  14. A systematic review on animal models of maternal high fat feeding and offspring glycaemic control.

    PubMed

    Ainge, H; Thompson, C; Ozanne, S E; Rooney, K B

    2011-03-01

    The mechanistic link between obese parents and obese offspring and the relative role of genes, and a shared environment is not completely understood. Animal models help us to differentiate between genetic and environmental factors, and the interaction between the two. However, the willingness of researchers to blend results from multiple models makes it difficult for clear mechanisms to be identified for specific hypothesis-driven research. As such we conducted a systematic review of animal models of maternal high fat feeding in an effort to identify the affect on the offspring glycaemic control. Maternal and offspring outcomes are reported in an effort to identify possible relationships to facilitate and focus on future research. We present here data from 11 studies investigating glycaemic control in offspring exposed to a high fat diet (HFD) during maternal gestation only or gestation and lactation. Studies in this review identify a real risk of type 2 diabetes and obesity in male offspring exposed to a maternal HFD. Poor glycaemic control in the offspring appears to be independent of maternal obesity, birth weight or post-weaning macronutrient intake. Inconsistencies between studies however, limit our capacity to identify mechanisms for the developmental origin of these diseases in animal models of overnutrition.

  15. Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

    PubMed Central

    Nizari, Shereen; Carare, Roxana O.; Hawkes, Cheryl A.

    2016-01-01

    Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer’s disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD. PMID:26911528

  16. Liking for high fat foods in patients with Obstructive Sleep Apnoea.

    PubMed

    Smith, Simon S; Waight, Catherine; Doyle, Geoffrey; Rossa, Kalina R; Sullivan, Karen A

    2014-07-01

    Excess weight and obesity are factors that are strongly associated with risk for Obstructive Sleep Apnoea (OSA). Weight loss has been associated with improvements in clinical indicators of OSA severity; however, patients' beliefs about diet change have not been investigated. This study utilized a validated behaviour change model to estimate the relationship between food liking, food intake and indices of OSA severity. Two-hundred and six OSA patients recruited from a Sleep Disorders Clinic completed standardized questionnaires of: a) fat and fibre food intake, food liking, and food knowledge and; b) attitudes and intentions towards fat reduction. OSA severity and body mass index (BMI) were objectively measured using standard clinical guidelines. The relationship between liking for high fat food and OSA severity was tested with hierarchical regression. Gender and BMI explained a significant 20% of the variance in OSA severity, Fibre Liking accounted for an additional 6% (a negative relationship), and Fat Liking accounted for a further 3.6% of variance. Although the majority of individuals (47%) were currently "active" in reducing fat intake, overall the patients' dietary beliefs and behaviours did not correspond. The independent relationship between OSA severity and liking for high fat foods (and disliking of high fibre foods) may be consistent with a two-way interaction between sleep disruption and food choice. Whilst the majority of OSA patients were intentionally active in changing to a healthy diet, further emphasis on improving healthy eating practices and beliefs in this population is necessary.

  17. Effects of High Fat Feeding on Liver Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Almon, Richard R.; DuBois, Debra C.; Sukumaran, Siddharth; Wang, Xi; Xue, Bai; Nie, Jing; Jusko, William J.

    2012-01-01

    Effects of high fat diet (HFD) on obesity and, subsequently, on diabetes are highly variable and modulated by genetics in both humans and rodents. In this report, we characterized the response of Goto-Kakizaki (GK) rats, a spontaneous polygenic model for lean diabetes and healthy Wistar-Kyoto (WKY) controls, to high fat feeding from weaning to 20 weeks of age. Animals fed either normal diet or HFD were sacrificed at 4, 8, 12, 16 and 20 weeks of age and a wide array of physiological measurements were made along with gene expression profiling using Affymetrix gene array chips. Mining of the microarray data identified differentially regulated genes (involved in inflammation, metabolism, transcription regulation, and signaling) in diabetic animals, as well as the response of both strains to HFD. Functional annotation suggested that HFD increased inflammatory differences between the two strains. Chronic inflammation driven by heightened innate immune response was identified to be present in GK animals regardless of diet. In addition, compensatory mechanisms by which WKY animals on HFD resisted the development of diabetes were identified, thus illustrating the complexity of diabetes disease progression. PMID:23236253

  18. Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization.

    PubMed

    Blevins, James E; Thompson, Benjamin W; Anekonda, Vishwanath T; Ho, Jacqueline M; Graham, James L; Roberts, Zachary S; Hwang, Bang H; Ogimoto, Kayoko; Wolden-Hanson, Tami; Nelson, Jarrell; Kaiyala, Karl J; Havel, Peter J; Bales, Karen L; Morton, Gregory J; Schwartz, Michael W; Baskin, Denis G

    2016-04-01

    Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.

  19. Diet-induced changes in the Lean Brain: Hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region.

    PubMed

    Koopman, Karin Eva; Booij, Jan; Fliers, Eric; Serlie, Mireille Johanna; la Fleur, Susanne Eva

    2013-01-01

    It is evident that there is a relationship between the brain's serotonin system and obesity. Although it is clear that drugs affecting the serotonin system regulate appetite and food intake, it is unclear whether changes in the serotonin system are cause or consequence of obesity. To determine whether obesogenic eating habits result in reduced serotonin transporter (SERT)-binding in the human hypothalamic region, we included 25 lean, male subjects who followed a 6-week-hypercaloric diet, which were high-fat-high-sugar (HFHS) or high-sugar (HS) with increased meal size or -frequency (=snacking pattern). We measured SERT-binding in the hypothalamic region with SPECT. All hypercaloric diets significantly increased body weight by 3-3.5%. Although there were no differences in total calories consumed between the diets, only a hypercaloric HFHS-snacking diet decreased SERT-binding significantly by 30%. We here show for the first time in humans that snacking may change the serotonergic system increasing the risk to develop obesity.

  20. Supplementing chicken broth with monosodium glutamate reduces energy intake from high fat and sweet snacks in middle-aged healthy women.

    PubMed

    Imada, Toshifumi; Hao, Susan Shuzhen; Torii, Kunio; Kimura, Eiichiro

    2014-08-01

    Monosodium L-glutamate (MSG) and inosine monophosphate-5 (IMP) are flavor enhancers for umami taste. However, their effects on appetite and food intake are not well-researched. The objective of the current study was to test their additions in a broth preload on subsequent appetite ratings, energy intake and food choice. Eighty-six healthy middle-aged women with normal body weight received three preload conditions on 3 test days 1 week apart - a low-energy chicken flavor broth (200 ml) as the control preload, and broths with added MSG alone (0.5 g/100 ml, MSG broth) or in combination with IMP (0.05 g/100 ml) (MSG+ broth) served as the experimental conditions. Fifteen minutes after preload administration subjects were provided an ad libitum testing meal which consisted of 16 snacks varying in taste and fat content. MSG and MSG+ enhanced savory taste and broth properties of liking and pleasantness. In comparison with control, the MSG preload resulted in less consumption of total energy, as well as energy from sweet and high-fat snacks. Furthermore, MSG broth preload reduced added sugar intake. These findings were not observed after MSG+ preload. Appetite ratings were not different across the three preloads. Results suggest a potential role of MSG addition to a low-energy broth preload in subsequent energy intake and food choice. This trial was registered at clinicaltrials.gov as NCT01761045.

  1. Metabolic and Testicular Effects of the Long-Term Administration of Different High-Fat Diets in Adult Rats

    PubMed Central

    Campos-Silva, Pamella; Furriel, Angelica; Costa, Waldemar S.; Sampaio, Francisco J. B.; Gregório, Bianca M.

    2015-01-01

    ABSTRACT Purpose: To evaluate the effects of different high-fat diets on body mass, carbohydrate metabolism and testicular morphology in rats seven months old. Materials and Methods: Male Wistar rats were divided into four groups: SC (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood samples, testes and genital fat deposits were collected for analysis. Data were analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as statistically significant. Results: Different high-fat diets promoted an increase in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC group (p=0.0010). Conclusions: The high fat diet administration, independent of the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard) alters the carbohydrate metabolism and the testicular morphology with reductions of seminiferous epithelium height, seminiferous tubule diameter and cell proliferation which could be related to a disturbance of spermatogenesis. PMID:26200553

  2. Antioxidant and hepatoprotective effects of fermented red ginseng against high fat diet-induced hyperlipidemia in rats.

    PubMed

    Kim, Myeong-Hwan; Lee, Eun-Jin; Cheon, Jeong-Mu; Nam, Ki-Jun; Oh, Tae-Ho; Kim, Kil-Soo

    2016-12-01

    This study was performed to investigate the antioxidant and hepatoprotective effects of fermented red ginseng (Panax ginseng C.A. Meyer; FRG) on high-fat diet-induced hyperlipidemia in rats. Sprague-Dawley rats were divided into four groups of seven: normal control, NC; high-fat diet control, HFC; high-fat diet-0.5% FRG, HF-FRGL; and high-fat diet-1% FRG, HF-FRGH. All rats were fed a high-fat diet for eight weeks, except those in the NC group, while rats in the FRG treatment groups received drinking water containing 0.5% or 1% FRG. After eight weeks of treatment, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in the serum were measured. The concentration of the oxidative stress marker malondialdehyde (MDA), and activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in rat liver were evaluated. Histological analysis of the liver was performed using hematoxylin and eosin. The high-fat diet markedly increased serum levels of ALT, AST, TC, TG, and LDL-C and hepatic MDA levels, while administration of FRG to the hyperlipidemic rats resulted in a significant decline in the levels of these parameters. Furthermore, the decline in the levels of serum HDL-C and hepatic SOD, CAT, and GSH-Px induced by the high-fat diet was attenuated by FRG treatment. In addition, histopathological analysis of liver sections suggested that FRG treatment also provided protection against liver damage. These results suggested that FRG improved lipid profiles, inhibited lipid peroxidation, and played a protective role against liver injury in hyperlipidemic rats.

  3. Antioxidant and hepatoprotective effects of fermented red ginseng against high fat diet-induced hyperlipidemia in rats

    PubMed Central

    Kim, Myeong-Hwan; Lee, Eun-Jin; Cheon, Jeong-Mu; Nam, Ki-Jun; Oh, Tae-Ho

    2016-01-01

    This study was performed to investigate the antioxidant and hepatoprotective effects of fermented red ginseng (Panax ginseng C.A. Meyer; FRG) on high-fat diet-induced hyperlipidemia in rats. Sprague-Dawley rats were divided into four groups of seven: normal control, NC; high-fat diet control, HFC; high-fat diet–0.5% FRG, HF-FRGL; and high-fat diet–1% FRG, HF-FRGH. All rats were fed a high-fat diet for eight weeks, except those in the NC group, while rats in the FRG treatment groups received drinking water containing 0.5% or 1% FRG. After eight weeks of treatment, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in the serum were measured. The concentration of the oxidative stress marker malondialdehyde (MDA), and activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in rat liver were evaluated. Histological analysis of the liver was performed using hematoxylin and eosin. The high-fat diet markedly increased serum levels of ALT, AST, TC, TG, and LDL-C and hepatic MDA levels, while administration of FRG to the hyperlipidemic rats resulted in a significant decline in the levels of these parameters. Furthermore, the decline in the levels of serum HDL-C and hepatic SOD, CAT, and GSH-Px induced by the high-fat diet was attenuated by FRG treatment. In addition, histopathological analysis of liver sections suggested that FRG treatment also provided protection against liver damage. These results suggested that FRG improved lipid profiles, inhibited lipid peroxidation, and played a protective role against liver injury in hyperlipidemic rats. PMID:28053615

  4. The Effects of High-fat-diet Combined with Chronic Unpredictable Mild Stress on Depression-like Behavior and Leptin/LepRb in Male Rats

    PubMed Central

    Yang, Jin Ling; Liu, De Xiang; Jiang, Hong; Pan, Fang; Ho, Cyrus SH; Ho, Roger CM

    2016-01-01

    Leptin plays a key role in the pathogenesis of obesity and depression via the long form of leptin receptor (LepRb). An animal model of comorbid obesity and depression induced by high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS) was developed to study the relationship between depression/anxiety-like behavior, levels of plasma leptin and LepRb in the brains between four groups of rats, the combined obesity and CUMS (Co) group, the obese (Ob) group, the CUMS group and controls. Our results revealed that the Co group exhibited most severe depression-like behavior in the open field test (OFT), anxiety-like behavior in elevated plus maze test (EMT) and cognitive impairment in the Morris water maze (MWM). The Ob group had the highest weight and plasma leptin levels while the Co group had the lowest levels of protein of LepRb in the hypothalamus and hippocampus. Furthermore, depressive and anxiety-like behaviors as well as cognitive impairment were positively correlated with levels of LepRb protein and mRNA in the hippocampus and hypothalamus. The down-regulation of leptin/LepRb signaling might be associated with depressive-like behavior and cognitive impairment in obese rats facing chronic mild stress. PMID:27739518

  5. Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung

    PubMed Central

    Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

    2017-01-01

    Background/Objectives: Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. Methods: We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Results: Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. Conclusions: These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring. PMID:28218737

  6. Fat substitutes promote weight gain in rats consuming high-fat diets

    PubMed Central

    Swithers, Susan E.; Ogden, Sean B.; Davidson, Terry L.

    2011-01-01

    The use of food products designed to mimic the sensory properties of sweet and fat while providing fewer calories has been promoted as a method for reducing food intake and body weight. However, such products may interfere with one mechanism that animals use to regulate energy balance, a learned relationship between the sensory properites of food and the caloric consequences of consuming those foods. Consistent with this hypothesis, previous data have shown that providing rats with sweet tastes that are not associated with the delivery of calories using high-intensity sweeteners results in increased food intake, body weight and adiposity, but only if the diet on which they are maintained also tastes sweet. In the present experiment, we examined whether use of the fat substitute, olestra, would have similar consequences by comparing the effects of consuming high-fat, high-calorie potato chips to the effects of consuming potato chips that sometimes signalled high calories (using high-fat potato chips) and that sometimes signalled lower calories (using non-fat potato chips manufactured with the fat substitute olestra). The results demonstrated that food intake, body weight gain and adiposity were greater for rats that consumed both the high-calorie chips and the low-calorie chips with olestra compared to rats that consumed consuming only the high-calorie chips, but only if animals were also consuming a chow diet that was high in fat and calories. When animals were maintained on a low-fat chow diet, intake, weight gain, and adiposity did not differ significantly based on chip type. However, rats previously exposed to both the low-calorie chips with olestra and the high-calorie chips exhibited increased body weight gain, food intake and adiposity when they were provided with a high fat, high calorie chow diet, even though the potato chips were no longer available. This suggests that the experience with the chips containing olestra affected the ability to predict high

  7. A high-fat diet raises fasting plasma CCK but does not affect upper gut motility, PYY, and ghrelin, or energy intake during CCK-8 infusion in lean men.

    PubMed

    Little, Tanya J; Feltrin, Kate L; Horowitz, Michael; Meyer, James H; Wishart, Judith; Chapman, Ian M; Feinle-Bisset, Christine

    2008-01-01

    There is evidence from studies in animals that the effects of both fat and CCK on gastrointestinal function and energy intake are attenuated by consumption of a high-fat diet. In humans, the effects of exogenous CCK-8 on antropyloroduodenal motility, plasma CCK, peptide YY (PYY), and ghrelin concentrations, appetite, and energy intake are attenuated by a high-fat diet. Ten healthy lean males consumed isocaloric diets (~15,400 kJ per day), containing either 44% (high-fat, HF) or 9% (low-fat, LF) fat, for 21 days in single-blind, randomized, cross-over fashion. Immediately following each diet (i.e., on day 22), subjects received a 45-min intravenous infusion of CCK-8 (2 ng.kg(-1).min(-1)), and effects on antropyloroduodenal motility, plasma CCK, PYY, ghrelin concentrations, hunger, and fullness were determined. Thirty minutes after commencement of the infusion, subjects were offered a buffet-style meal, from which energy intake (in kilojoules) was quantified. Body weight was unaffected by the diets. Fasting CCK (P < 0.05), but not PYY and ghrelin, concentrations were greater following the HF, compared with the LF, diet. Infusion of CCK-8 stimulated pyloric pressures (P < 0.01) and suppressed antral and duodenal pressures (P < 0.05), with no difference between the diets. Energy intake also did not differ between the diets. Short-term consumption of a HF diet increases fasting plasma CCK concentrations but does not affect upper gut motility, PYY and ghrelin, or energy intake during CCK-8 infusion, in a dose of 2 ng.kg(-1).min(-1), in healthy males.

  8. Effects of protein and carbohydrate meals on mood and performance: interactions with sex and age.

    PubMed

    Spring, B; Maller, O; Wurtman, J; Digman, L; Cozolino, L

    Normal adult subjects (n = 184) consumed a high-protein or high-carbohydrate meal. Two hours later their mood and performance were tested. The effects of meal composition on mood were different for men and women, and for older and younger subjects. Females, but not males, reported greater sleepiness after a carbohydrate as opposed to a protein meal. Male subjects, but not females, reported greater calmness after a carbohydrate as opposed to a protein meal. Older subjects responded differently to meals depending upon the time of day when these were consumed. When meals were eaten for breakfast (but not for lunch) individuals 40 yr of age or older felt more tense and less calm after a protein than after a carbohydrate meal. Although older subjects reported subjective discomfort after a morning protein meal, they displayed objective performance impairments after a carbohydrate lunch. Subjects 40 yr of age or older were impaired on a test of sustained selective attention (dichotic shadowing) after consuming a high-carbohydrate lunch. The shadowing impairment after carbohydrate consumption was as pronounced without distraction as with distraction and resulted mostly from increased omission errors. Our findings suggest negative effects on concentration when older subjects consume a high-carbohydrate, low-protein lunch. These negative effects of carbohydrate consumption appear to arise predominantly from lapses of attention rather than from intrusion of distractors.

  9. Swimming exercise reduces preference for a high-fat diet by increasing insulin sensitivity in C57BL/6 mice.

    PubMed

    Wang, Hai-Jun; Yang, Hong-Tao; Chen, Wei

    2017-01-01

    The present study examined the effect of 4-week swimming training on the preference for a high-fat diet and insulin sensitivity in mice. C57BL/6 J mice were placed on either a low-fat diet or a choice diet (with both low-fat and high-fat diets available) for 6 weeks. During this period, a group of mice on the free-choice diet were randomly selected to receive a 4-week swimming exercise intervention. Mice that received the swimming exercise intervention showed a reduced preference for the high-fat diet as well as a slower rate of weight gain. Moreover, changes in insulin sensitivity, tyrosine hydroxylase expression in the ventral tegmental area-nucleus accumbens system, and the expression of IRS2, IRS2, and high-fat diet-induced Akt phosphorylation in the nucleus accumbens were delayed in the swimming exercise intervention group. Taken together, these results suggest that swimming exercise regulates the dopaminergic reward system to decrease high-fat diet intake, thereby controlling body weight to prevent obesity, in a manner likely mediated by increased insulin signal transduction in the nucleus accumbens.

  10. Effects of adrenalectomy on energy balance in obese (ob/ob) mice fed high carbohydrate or high fat diets.

    PubMed

    Grogan, C K; Kim, H K; Romsos, D R

    1987-06-01

    We reported previously that adrenalectomy reduced the energy density of body weight gain (an indicator of proportional gain in lean and fat tissue) and the efficiency of energy retention in obese (ob/ob) mice to values approximating those in lean mice, but that adrenalectomy had much less influence on these parameters in ob/ob mice fed a purified high fat diet. To determine if fat was the exclusive factor in the purified high fat diet that negated effects of adrenalectomy, ob/ob mice were fed a purified high carbohydrate (glucose) diet identical in composition to the high fat diet, except for the fat/carbohydrate ratio. Responses of adrenalectomized ob/ob mice fed the purified high glucose diet from 4 to 7 wk of age mimicked those of mice fed the purified high fat diet, not those of mice fed the high carbohydrate nonpurified diet. Plasma glucose responses to a glucose load in adrenalectomized ob/ob mice paralleled the diet-dependent changes in energy balance. These results demonstrate that diet composition interacts with adrenal secretions to influence energy and glucose metabolism in ob/ob mice; consumption of either a purified high glucose or high fat diet negates the beneficial effects of adrenalectomy on energy and glucose metabolism observed when adrenalectomized ob/ob mice consume a nonpurified diet.

  11. Antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in rats fed a high fat diet

    PubMed Central

    2010-01-01

    Background Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The purpose of this study was to investigate the antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in high fat diet-induced obese rats. Methods Four week-old male Sprague-Dawley rats were randomly divided into four groups with 8 rats in each group for a period of 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf hot water extract, HFL group; high fat diet + lotus leaf hot water extract + taurine, HFLT group). Lotus leaf hot water extract was orally administrated to HFL and HFLT groups and the same amount of distilled water was orally administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). Results The body weight gain and relative weights of epididymal and retroperitoneal adipose tissues were significantly lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed lower concentrations of total cholesterol, triglyceride and low density lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT group showed better blood lipid profiles compared to HFL group. Conclusions Lotus leaf hot water extract with taurine supplementation showed antiobesity and hypolipidemic effects in high fat diet-induced obese rats, which was more effective than lotus leaf hot water extract alone. PMID:20804619

  12. Efficacy of Garcinia Cambogia on Body Weight, Inflammation and Glucose Tolerance in High Fat Fed Male Wistar Rats

    PubMed Central

    Sripradha, Ramalingam

    2015-01-01

    Introduction: Obesity leads to derangements in lipid and glucose homeostasis resulting in various metabolic complications. Plants containing vital phytochemicals are known to posses anti obesity properties and have proved to exert beneficial effects in obesity. Objectives: The present study was aimed to investigate the effects of Garcinia Cambogia on body weight, glucose tolerance and inflammation in high fat diet fed male Wistar rats. Materials and Methods: Five month old male wistar rats (n=40) were divided into four groups. Two groups were fed with standard rodent diet and the remaining two with 30% high fat diet. One group in each of the two sets received the crude ethanolic extract of Garcinia Cambogia at a dose of 400mg/kg body weight/day for ten weeks. Body weight, intraperitoneal glucose tolerance test, leptin, tumour necrosis factor-α (TNF-α) and renal function (urea, creatinine, uric acid) were studied. Results: High fat diet fed rats showed increased body weight gain, glucose intolerance, elevated levels of plasma leptin and TNF-α. Supplementation of Garcinia Cambogia extract (GE) along with high fat diet significantly decreased body weight gain, glucose intolerance, plasma leptin and TNF-α level. No significant changes were observed in the renal function parameters in any of the groups. Conclusion: Supplementation of the Garcinia Cambogia extract with high fat diet reduced body weight gain, inflammation and glucose intolerance. PMID:25859449

  13. Evaluation of Beneficial Metabolic Effects of Berries in High-Fat Fed C57BL/6J Mice

    PubMed Central

    Blanco, Narda; Sterner, Olov; Holm, Cecilia

    2014-01-01

    Objective. The aim of the study was to screen eight species of berries for their ability to prevent obesity and metabolic abnormalities associated with type 2 diabetes. Methods. C57BL/6J mice were assigned the following diets for 13 weeks: low-fat diet, high-fat diet or high-fat diet supplemented (20%) with lingonberry, blackcurrant, bilberry, raspberry, açai, crowberry, prune or blackberry. Results. The groups receiving a high-fat diet supplemented with lingonberries, blackcurrants, raspberries or bilberries gained less weight and had lower fasting insulin levels than the control group receiving high-fat diet without berries. Lingonberries, and also blackcurrants and bilberries, significantly decreased body fat content, hepatic lipid accumulation, and plasma levels of the inflammatory marker PAI-1, as well as mediated positive effects on glucose homeostasis. The group receiving açai displayed increased weight gain and developed large, steatotic livers. Quercetin glycosides were detected in the lingonberry and the blackcurrant diets. Conclusion. Lingonberries were shown to fully or partially prevent the detrimental metabolic effects induced by high-fat diet. Blackcurrants and bilberries had similar properties, but to a lower degree. We propose that the beneficial metabolic effects of lingonberries could be useful in preventing obesity and related disorders. PMID:24669315

  14. Maternal methyl donors supplementation during lactation prevents the hyperhomocysteinemia induced by a high-fat-sucrose intake by dams.

    PubMed

    Cordero, Paul; Milagro, Fermin I; Campion, Javier; Martinez, J Alfredo

    2013-12-16

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle.

  15. Maternal Methyl Donors Supplementation during Lactation Prevents the Hyperhomocysteinemia Induced by a High-Fat-Sucrose Intake by Dams

    PubMed Central

    Cordero, Paul; Milagro, Fermin I.; Campion, Javier; Martinez, J. Alfredo

    2013-01-01

    Maternal perinatal nutrition may program offspring metabolic features. Epigenetic regulation is one of the candidate mechanisms that may be affected by maternal dietary methyl donors intake as potential controllers of plasma homocysteine levels. Thirty-two Wistar pregnant rats were randomly assigned into four dietary groups during lactation: control, control supplemented with methyl donors, high-fat-sucrose and high-fat-sucrose supplemented with methyl donors. Physiological outcomes in the offspring were measured, including hepatic mRNA expression and global DNA methylation after weaning. The newborns whose mothers were fed the obesogenic diet were heavier longer and with a higher adiposity and intrahepatic fat content. Interestingly, increased levels of plasma homocysteine induced by the maternal high-fat-sucrose dietary intake were prevented in both sexes by maternal methyl donors supplementation. Total hepatic DNA methylation decreased in females due to maternal methyl donors administration, while Dnmt3a hepatic mRNA levels decreased accompanying the high-fat-sucrose consumption. Furthermore, a negative association between Dnmt3a liver mRNA levels and plasma homocysteine concentrations was found. Maternal high-fat-sucrose diet during lactation could program offspring obesity features, while methyl donors supplementation prevented the onset of high hyperhomocysteinemia. Maternal dietary intake also affected hepatic DNA methylation metabolism, which could be linked with the regulation of the methionine-homocysteine cycle. PMID:24351826

  16. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice.

    PubMed

    Hu, Yueshan; Davies, Gareth E

    2010-07-01

    Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARgamma expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

  17. Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting.

    PubMed

    Hatting, Maximilian; Rines, Amy K; Luo, Chi; Tabata, Mitsuhisa; Sharabi, Kfir; Hall, Jessica A; Verdeguer, Francisco; Trautwein, Christian; Puigserver, Pere

    2017-02-07

    A promising approach to treating obesity is to increase diet-induced thermogenesis in brown adipose tissue (BAT), but the regulation of this process remains unclear. Here we find that CDC-like kinase 2 (CLK2) is expressed in BAT and upregulated upon refeeding. Mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting. Additionally, tissue oxygen consumption and protein levels of UCP1 are reduced in CLK2-deficient BAT. Phosphorylation of CREB, a transcriptional activator of UCP1, is markedly decreased in BAT cells lacking CLK2 due to enhanced CREB dephosphorylation. Mechanistically, CREB dephosphorylation is rescued by the inhibition of PP2A, a phosphatase that targets CREB. Our results suggest that CLK2 is a regulatory component of diet-induced thermogenesis in BAT through increased CREB-dependent expression of UCP1.

  18. The effect of a high fat diet on pyruvate decarboxylase deficiency without central nervous system involvement.

    PubMed

    Kodama, S; Yagi, R; Ninomiya, M; Goji, K; Takahashi, T; Morishita, Y; Matsuo, T

    1983-01-01

    A nine-year-old Japanese boy with low pyruvate decarboxylase activity in fibroblasts showed no central nervous symptoms except for muscle fatigue. The pyruvate decarboxylase activities in fibroblasts of the patient and two control subjects were 0.407 +/- 0.083, 1.029 +/- 0.137 and 1.607 +/- 0.096 mumoles/g protein/30 min, respectively. The Michaelis-Menten constant (Km) was the same in the patient and controls. There was no inhibitor of pyruvate decarboxylase in the patient's fibroblasts. A high fat diet has been given to the patient for five years. At present he does not complain of any kind of muscle fatigue, except after severe exercise. Mental and physiological development of the patient are within the normal ranges. However, trials of orally administered thiamine hydrochloride or thiamine hydrochloride combined with lipoamide did not improve his muscle fatigue.

  19. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  20. STORAGE, NUTRITIONAL AND SENSORY PROPERTIES OF HIGH-FAT FISH AND RICE FLOUR COEXTRUDATES

    SciTech Connect

    Jaya Shankar Tumuluru; Shahab Sokhansanj; Sukumar Bandyopadhyay; Amarender Singh Bawa

    2013-10-01

    The present research is on understanding the storage, nutritional and sensory characteristics of high-fat fish (khoira) and rice flour coextrudates at storage temperature of 30C. The extruder processing conditions used are barrel temperature (200C), screw speed (109 rpm), fish content of feed (44%) and feed moisture content (39%). Sorption isotherm data indicated that the safe aw level was about 0.4–0.7. Guggenheim -Anderson -de Boer model described the sorption data adequately with an r2 value of 0.99. During the initial 15 days of storage, there was a loss of vitamin A and total tocopherols by 64.4 and 20.6%, and an increase in peroxides and free fatty acid content by about 116 mg/kg and 21.7%. The nonlinear mathematical model developed has adequately described the changes in nutritional and storage properties. Sensory attributes indicated that the product fried for 15 s was most acceptable.

  1. Parental high-fat programming of offspring development, health and β-cells.

    PubMed

    Cerf, Marlon E

    2011-01-01

    Recent studies extend the concept of developmental and adaptive plasticity to include a paternal role in the programming of metabolic disease, including diabetes. Parents greatly influence the development and health of their offspring. Although genetic imprinting plays a major role in determining offspring health outcomes, non-genetic transmission is also a critical determinant. Programming by parental high-fat feeding has demonstrated adverse effects on β-cell development and function in offspring. However, maternal and paternal programming effects vary in their potency, with mothers holding the greater influence due to their direct involvement in offspring development and health. Maintenance of parental health pre-conception and during the early phases of offspring life is critical to improve health outcomes of offspring, with the benefit of positive effects on parental health. Preservation and protection of β-cells throughout offspring life, even before conception, is a strategy to enhance β-cell survival in offspring.

  2. Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats

    PubMed Central

    Kołodziej, Urszula; Maciejczyk, Mateusz; Miąsko, Agnieszka; Matczuk, Jan; Knaś, Małgorzata; Żukowski, Piotr; Żendzian-Piotrowska, Małgorzata; Borys, Jan; Zalewska, Anna

    2017-01-01

    Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet. PMID:28184199

  3. Additive Effects of Nicotine and High-Fat Diet on Hepatic Steatosis in Male Mice

    PubMed Central

    Friedman, Theodore C.; Sinha-Hikim, Indrani; Parveen, Meher; Najjar, Sonia M.; Liu, Yanjun; Mangubat, Michael; Shin, Chang-Sung; Lyzlov, Alexei; Ivey, Rasheed; Shaheen, Magda; French, Samuel W.

    2012-01-01

    Smoking is a major risk factor for diabetes and cardiovascular disease and may contribute to nonalcoholic fatty liver disease. We hypothesize that in the presence of nicotine, high-fat diet (HFD) causes more severe hepatic steatosis in obese mice. Adult C57BL6 male mice were fed a normal chow diet or HFD and received twice daily injections of nicotine (0.75 mg/kg body weight, ip) or saline for 10 wk. Light microscopic image analysis revealed significantly higher lipid accumulation in livers from mice on HFD plus nicotine (190 ± 19 μm2), compared with mice on HFD alone (28 ± 1.2 μm2). A significant reduction in the percent volume of endoplasmic reticulum (67.8%) and glycogen (49.2%) was also noted in hepatocytes from mice on HFD plus nicotine, compared with mice on HFD alone. The additive effects of nicotine on the severity of HFD-induced hepatic steatosis was associated with significantly greater oxidative stress, increased hepatic triglyceride levels, higher incidence of hepatocellular apoptosis, inactivation (dephosphorylation) of AMP-activated protein kinase, and activation of its downstream target acetyl-coenzyme A-carboxylase. Treatment with acipimox, an inhibitor of lipolysis, significantly reduced nicotine plus HFD-induced hepatic lipid accumulation. We conclude that: 1) greater oxidative stress coupled with inactivation of AMP-activated protein kinase mediate the additive effects of nicotine and HFD on hepatic steatosis in obese mice and 2) increased lipolysis is an important contributor to hepatic steatosis. We surmise that nicotine exposure is likely to exacerbate the metabolic abnormalities induced by high-fat intake in obese patients. PMID:23093702

  4. Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats.

    PubMed

    Kołodziej, Urszula; Maciejczyk, Mateusz; Miąsko, Agnieszka; Matczuk, Jan; Knaś, Małgorzata; Żukowski, Piotr; Żendzian-Piotrowska, Małgorzata; Borys, Jan; Zalewska, Anna

    2017-01-01

    Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet.

  5. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    SciTech Connect

    Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  6. Reduction of weight loss and tumour size in a cachexia model by a high fat diet.

    PubMed Central

    Tisdale, M. J.; Brennan, R. A.; Fearon, K. C.

    1987-01-01

    An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour. PMID:3620317

  7. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice.

    PubMed

    Gu, Yeyi; Yu, Shan; Park, Jong Yung; Harvatine, Kevin; Lambert, Joshua D

    2014-04-01

    In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 weeks. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40-60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cyclooxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia.

  8. Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet.

    PubMed

    Lee, Michelle; Kim, Andrea; Chua, Streamson C; Obici, Silvana; Wardlaw, Sharon L

    2007-07-01

    To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH(2)-terminal POMC transgene that includes alpha- and gamma(3)-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD (P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD (P < 0.05) and were more pronounced on HFD (P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD (P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences.

  9. Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats

    PubMed Central

    Wang, Jian-qing; Zou, Yu-hong; Huang, Cheng; Lu, Chao; Zhang, Lei; Jin, Yong; Lü, Xiong-wen; Liu, Li-ping; Li, Jun

    2012-01-01

    Aim: To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats. Methods: Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively. Results: Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers. Conclusion: Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism. PMID:22543705

  10. Metabolic adaptations to a high-fat diet in endurance cyclists.

    PubMed

    Goedecke, J H; Christie, C; Wilson, G; Dennis, S C; Noakes, T D; Hopkins, W G; Lambert, E V

    1999-12-01

    We examined the time course of metabolic adaptations to 15 days of a high-fat diet (HFD). Sixteen endurance-trained cyclists were assigned randomly to a control (CON) group, who consumed their habitual diet (30% +/- 8% mJ fat), or a HFD group, who consumed a high-fat isocaloric diet (69% +/- 1% mJ fat). At 5-day intervals, the subjects underwent an oral glucose tolerance test (OGTT); on the next day, they performed a 2.5-hour constant-load ride at 70% peak oxygen consumption (VO2peak), followed by a simulated 40-km cycling time-trial while ingesting a 10% 14C-glucose + 3.44% medium-chain triglyceride (MCT) emulsion at a rate of 600 mL/h. In the OGTT, plasma glucose concentrations at 30 minutes increased significantly after 5 days of the HFD and remained elevated at days 10 and 15 versus the levels measured prior to the HFD (P < .05). The activity of carnitine acyltransferase (CAT) in biopsies of the vastus lateralis muscle also increased from 0.45 to 0.54 micromol/g/min over days 0 to 10 of the HFD (P < .01) without any change in citrate synthase (CS) or 3-hydroxyacyl-coenzyme A dehydrogenase (3-HAD) activities. Changes in glucose tolerance and CAT activity were associated with a shift from carbohydrate (CHO) to fat oxidation during exercise (P < .001), which occurred within 5 to 10 days of the HFD. During the constant-load ride, the calculated oxidation of muscle glycogen was reduced from 1.5 to 1.0 g/min (P < .001) after 15 days of the HFD. Ingestion of a HFD for as little as 5 to 10 days significantly altered substrate utilization during submaximal exercise but did not attenuate the 40-km time-trial performance.

  11. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    PubMed Central

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-01-01

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. PMID:21983427

  12. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    SciTech Connect

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-12-15

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

  13. Beneficial effects of Plantago albicans on high-fat diet-induced obesity in rats.

    PubMed

    Samout, Noura; Ettaya, Amani; Bouzenna, Hafsia; Ncib, Sana; Elfeki, Abdelfattah; Hfaiedh, Najla

    2016-12-01

    Obesity is a one of the main global public health problems associated with chronic diseases such as coronary heart disease, diabetes and cancer. As a solution to obesity, we suggest Plantago albicans, which is a medicinal plant with several biological effects. This study assesses the possible anti-obesity protective properties of Plantago albicans in high fat diet-fed rats. 28 male Wistar rats were divided into 4 groups; a group which received normal diet (C), the second group was fed HDF diet (HDF), the third group was given normal diet supplemented with Plantago albicans (P.AL), and the fourth group received HDF supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our results showed an increase in body weight of HDF rats by ∼16% as compared to the control group with an increase in the levels of total cholesterol (TC) as well as LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS increased in the liver and heart of HDF-fed rats as compared to the control group. The oral gavage of Plantago albicans extract to obese rats induced a reduction in their body weight, lipid accumulation in liver and heart tissue, compared to the high-fat diet control rats. The obtained results proved that the antioxidant potency of Plantago albicans extracts was correlated with their phenolic and flavonoid contents. The antioxidant capacity of the extract was evaluated by DPPH test (as EC50=250±2.12μg/mL) and FRAP tests (as EC50=27.77±0.14μg/mL). These results confirm the phytochemical and antioxidant impact of Plantago albicans extracts. Plantago albicans content was determined using validated HPLC methodology.

  14. High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation: Role of endoplasmic-reticulum-stress

    PubMed Central

    Coucha, Maha; Mohamed, Islam N; Elshaer, Sally L; Mbata, Osinakachuk; Bartasis, Megan L; El-Remessy, Azza B

    2017-01-01

    AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid (PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin (BSA) (400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, miR-17-5p mRNA, as well as nucleotide-binding oligomerization domain-like receptor protein (NLRP3) and IL1β protein was determined. RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers (P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased miR-17-5p expression, which were restored by inhibiting endoplasmic reticulum-stress with PBA (P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced miR-17-5p and induced thioredoxin interacting protein mRNA in retinal Müller glial cell line (P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β. CONCLUSION Our work suggests that targeting endoplasmic reticulum-stress or thioredoxin interacting protein are potential therapeutic strategies for early

  15. Rats of hypertensive ISIAH strain are resistant to the development of metabolic syndrome induced by high-fat diet.

    PubMed

    Dushkin, M I; Khrapova, M V; Kovshik, G G; Chasovskikh, M I; Selyatitskaya, V G; Palchikova, N A

    2014-03-01

    We studied the influence of high-fat diet on the development of metabolic syndrome in rats of hypertensive ISIAH strain and normotensive WAG strain. In contrast to ISIAH rats, high-fat diet in WAG rats led visceral obesity, glucose tolerance, and dyslipidemia. DNA-binding activity of the peroxisome proliferator-activated receptor α (PPARα) decreased in the liver of WAG rats and increased in ISIAH rats. Blood levels of TNF-α, IL-6, and corticosterone increased more significantly in WAG rats. Corticosterone content in the adrenal glands was more markedly reduced in WAG rats. High-fat diet had no effect on BP in ISIAH and WAG rats. It was concluded that ISIAH rats can be used as a genetic model in studies of the mechanism of resistance to the metabolic syndrome.

  16. 29 CFR 785.19 - Meal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Meal. 785.19 Section 785.19 Labor Regulations Relating to... INTERPRETATION NOT DIRECTLY RELATED TO REGULATIONS HOURS WORKED Application of Principles Rest and Meal Periods § 785.19 Meal. (a) Bona fide meal periods. Bona fide meal periods are not worktime. Bona fide...

  17. Nutrient quality of fast food kids meals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure of children to kids’ meals at fast food restaurants is high; however, the nutrient quality of such meals has not been systematically assessed. We assessed the nutrient quality of fast food meals marketed to young children, i.e., "kids meals". The nutrient quality of kids’ meals was assessed...

  18. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

    PubMed Central

    Goossens, Gijs H.; Moors, Chantalle C. M.; Jocken, Johan W. E.; van der Zijl, Nynke J.; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E.

    2016-01-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  19. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

    PubMed

    Goossens, Gijs H; Moors, Chantalle C M; Jocken, Johan W E; van der Zijl, Nynke J; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E

    2016-03-14

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.

  20. Glucocorticoids Mediate Short-Term High-Fat Diet Induction of Neuroinflammatory Priming, the NLRP3 Inflammasome, and the Danger Signal HMGB1

    PubMed Central

    Sobesky, Julia L.; D’Angelo, Heather M.; Anderson, Nathan D.; Watkins, Linda R.; Maier, Steven F.

    2016-01-01

    Abstract The impact of the foods we eat on metabolism and cardiac physiology has been studied for decades, yet less is known about the effects of foods on the CNS, or the behavioral manifestations that may result from these effects. Previous studies have shown that long-term consumption of high-fat foods leading to diet-induced obesity sensitizes the inflammatory response of the brain to subsequent challenging stimuli, causing deficits in the formation of long-term memories. The new findings reported here demonstrate that short-term consumption of a high-fat diet (HFD) produces the same outcomes, thus allowing the examination of mechanisms involved in this process long before obesity and associated comorbidities occur. Rats fed an HFD for 3 d exhibited increases in corticosterone, the inflammasome-associated protein NLRP3 (nod-like receptor protein 3), and the endogenous danger signal HMGB1 (high-mobility group box 1) in the hippocampus. A low-dose (10 μg/kg) lipopolysaccharide (LPS) immune challenge potentiated the neuroinflammatory response in the hippocampus of rats fed the HFD, and caused a deficit in the formation of long-term memory, effects not observed in rats fed regular chow. The blockade of corticosterone action with the glucocorticoid receptor antagonist mifepristone prevented the NLRP3 and HMGB1 increases in unchallenged animals, normalized the proinflammatory response to LPS, and prevented the memory impairment. These data suggest that short-term HFD consumption increases vulnerability to memory disruptions caused by an immune challenge by upregulating important neuroinflammatory priming and danger signals in the hippocampus, and that these effects are mediated by increases in hippocampal corticosterone. PMID:27595136

  1. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation.

    PubMed

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-10-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut.

  2. Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD

    PubMed Central

    Luo, Yuwen; Burrington, Christine M.; Graff, Emily C.; Zhang, Jian; Judd, Robert L.; Suksaranjit, Promporn; Kaewpoowat, Quanhathai; Davenport, Samantha K.; O'Neill, Ann Marie

    2015-01-01

    nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression. PMID:26670487

  3. Glucocorticoids Mediate Short-Term High-Fat Diet Induction of Neuroinflammatory Priming, the NLRP3 Inflammasome, and the Danger Signal HMGB1.

    PubMed

    Sobesky, Julia L; D'Angelo, Heather M; Weber, Michael D; Anderson, Nathan D; Frank, Matthew G; Watkins, Linda R; Maier, Steven F; Barrientos, Ruth M

    2016-01-01

    The impact of the foods we eat on metabolism and cardiac physiology has been studied for decades, yet less is known about the effects of foods on the CNS, or the behavioral manifestations that may result from these effects. Previous studies have shown that long-term consumption of high-fat foods leading to diet-induced obesity sensitizes the inflammatory response of the brain to subsequent challenging stimuli, causing deficits in the formation of long-term memories. The new findings reported here demonstrate that short-term consumption of a high-fat diet (HFD) produces the same outcomes, thus allowing the examination of mechanisms involved in this process long before obesity and associated comorbidities occur. Rats fed an HFD for 3 d exhibited increases in corticosterone, the inflammasome-associated protein NLRP3 (nod-like receptor protein 3), and the endogenous danger signal HMGB1 (high-mobility group box 1) in the hippocampus. A low-dose (10 μg/kg) lipopolysaccharide (LPS) immune challenge potentiated the neuroinflammatory response in the hippocampus of rats fed the HFD, and caused a deficit in the formation of long-term memory, effects not observed in rats fed regular chow. The blockade of corticosterone action with the glucocorticoid receptor antagonist mifepristone prevented the NLRP3 and HMGB1 increases in unchallenged animals, normalized the proinflammatory response to LPS, and prevented the memory impairment. These data suggest that short-term HFD consumption increases vulnerability to memory disruptions caused by an immune challenge by upregulating important neuroinflammatory priming and danger signals in the hippocampus, and that these effects are mediated by increases in hippocampal corticosterone.

  4. Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet

    PubMed Central

    Jackson, Ellen E.; Rendina-Ruedy, Elisabeth; Smith, Brenda J.; Lacombe, Veronique A.

    2015-01-01

    Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway. PMID:26539824

  5. Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet.

    PubMed

    Jackson, Ellen E; Rendina-Ruedy, Elisabeth; Smith, Brenda J; Lacombe, Veronique A

    2015-01-01

    Diabetes is a chronic inflammatory disease that carries a high risk of cardiovascular disease. However, the pathophysiological link between these disorders is not well known. We hypothesize that TLR4 signaling mediates high fat diet (HFD)-induced peripheral and cardiac glucose metabolic derangements. Mice with a loss-of-function mutation in TLR4 (C3H/HeJ) and age-matched control (C57BL/6) mice were fed either a high-fat diet or normal diet for 16 weeks. Glucose tolerance and plasma insulin were measured. Protein expression of glucose transporters (GLUT), AKT (phosphorylated and total), and proinflammatory cytokines (IL-6, TNF-α and SOCS-3) were quantified in the heart using Western Blotting. Both groups fed a long-term HFD had increased body weight, blood glucose and insulin levels, as well as impaired glucose tolerance compared to mice fed a normal diet. TLR4-mutant mice were partially protected against long-term HFD-induced insulin resistance. In control mice, feeding a HFD decreased cardiac crude membrane GLUT4 protein content, which was partially rescued in TLR4-mutant mice. TLR4-mutant mice fed a HFD also had increased expression of GLUT8, a novel isoform, compared to mice fed a normal diet. GLUT8 content was positively correlated with SOCS-3 and IL-6 expression in the heart. No significant differences in cytokine expression were observed between groups, suggesting a lack of inflammation in the heart following a HFD. Loss of TLR4 function partially restored a healthy metabolic phenotype, suggesting that TLR4 signaling is a key mechanism in HFD-induced peripheral and cardiac insulin resistance. Our data further suggest that TLR4 exerts its detrimental metabolic effects in the myocardium through a cytokine-independent pathway.

  6. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    PubMed

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

  7. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.

    PubMed

    Ii, Hiromi; Yokoyama, Naoki; Yoshida, Shintaro; Tsutsumi, Kae; Hatakeyama, Shinji; Sato, Takashi; Ishihara, Keiichi; Akiba, Satoshi

    2009-12-01

    Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.

  8. Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

    PubMed

    Chang, Yuan-Yen; Chou, Chung-Hsi; Chiu, Chih-Hsien; Yang, Kuo-Tai; Lin, Yi-Ling; Weng, Wei-Lien; Chen, Yi-Chen

    2011-01-12

    Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.

  9. Effects of exercise and L-arginine intake on inflammation in aorta of high-fat diet induced obese rats

    PubMed Central

    Kim, Hee-jae; Son, Junseok; Jin, Eunhee; Lee, Jin; Park, Sok

    2016-01-01

    [Purpose] In the present study, we investigated the effect of exercise and arginine on the inflammatory makers and Cu-Mn superoxide dismutase (SOD) expression in the aortas of high-fat-induced obese rats. [Methods] Fifty 6-month-old male Sprague-Dawley rats were randomly assigned as follows: HF-Con: high-fat diet, HF-Ex: high-fat diet and exercise, HF-Ex+A: high-fat diet and combined exercise and arginine, HF-A: high-fat diet and arginine. The high-fat diet was fed for 12 weeks following 1 week of environmental adaptation with mixed solid chow. The rats performed treadmill exercise 6 times per week for 12 weeks at20 m/min for 60 min. L-argininewas mixed with saline and orally administered at 150 mg/kg once a day. Expressions of inflammatory markers (including NF- κB, TNF-α, COX-2) and SOD were evaluated using western blotting. [Results] NF-κB expression decreased significantly (p<0.05) in the HF-Ex group compared with HF-Con group, and we found additional effects(p<0.01) on NF-κB expression in HF-EX+A compared withHF-Ex. TNF-α expression decreased significantly (p<0.01) in HF-Ex, FH-Ex+A, and FH-A compared with HF-Con. In a similar trend with NF-κB expression, COX-2 expression decreased significantly in HF-Ex compared withHF-Con. In Cu-Mn SOD expression, there was no difference between HF and HF-Ex, but significant increases (p<0.01) inCu-Mn SOD werefound in HF-Ex+A and HF-A. [Conclusion] Based on our results, treatment that combines exercise and arginine might be effective for modulatingvascular inflammation and oxidative stress in obesity PMID:27298811

  10. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    SciTech Connect

    Kanno, Ayumi; Asahara, Shun-ichiro; Masuda, Katsuhisa; Matsuda, Tomokazu; Kimura-Koyanagi, Maki; Seino, Susumu; Ogawa, Wataru; Kido, Yoshiaki

    2015-03-13

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

  11. Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

    PubMed

    Heo, Jung-Yoon; Cha, Hye-Na; Kim, Ki Young; Lee, Eujin; Kim, Suk-Jeong; Kim, Yong-Woon; Kim, Jong-Yeon; Lee, In-Kyu; Gladyshev, Vadim N; Kim, Hwa-Young; Park, So-Young

    2017-01-01

    Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

  12. Liver fatty acid binding protein gene-ablation exacerbates weight gain in high-fat fed female mice.

    PubMed

    McIntosh, Avery L; Atshaves, Barbara P; Landrock, Danilo; Landrock, Kerstin K; Martin, Gregory G; Storey, Stephen M; Kier, Ann B; Schroeder, Friedhelm

    2013-05-01

    Loss of liver fatty acid binding protein (L-FABP) decreases long chain fatty acid uptake and oxidation in primary hepatocytes and in vivo. On this basis, L-FABP gene ablation would potentiate high-fat diet-induced weight gain and weight gain/energy intake. While this was indeed the case when L-FABP null (-/-) mice on the C57BL/6NCr background were pair-fed a high-fat diet, whether this would also be observed under high-fat diet fed ad libitum was not known. Therefore, this possibility was examined in female L-FABP (-/-) mice on the same background. L-FABP (-/-) mice consumed equal amounts of defined high-fat or isocaloric control diets fed ad libitum. However, on the ad libitum-fed high-fat diet the L-FABP (-/-) mice exhibited: (1) decreased hepatic long chain fatty acid (LCFA) β-oxidation as indicated by lower serum β-hydroxybutyrate level; (2) decreased hepatic protein levels of key enzymes mitochondrial (rate limiting carnitine palmitoyl acyltransferase A1, CPT1A; HMG-CoA synthase) and peroxisomal (acyl CoA oxidase 1, ACOX1) LCFA β-oxidation; (3) increased fat tissue mass (FTM) and FTM/energy intake to the greatest extent; and (4) exacerbated body weight gain, weight gain/energy intake, liver weight, and liver weight/body weight to the greatest extent. Taken together, these findings showed that L-FABP gene-ablation exacerbated diet-induced weight gain and fat tissue mass gain in mice fed high-fat diet ad libitum--consistent with the known biochemistry and cell biology of L-FABP.

  13. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    SciTech Connect

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  14. Extended multiplexing of TMT labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue.

    PubMed

    Plubell, Deanna L; Wilmarth, Phillip A; Zhao, Yuqi; Fenton, Alexandra M; Minnier, Jessica; Reddy, Ashok P; Klimek, John; Yang, Xia; David, Larry L; Pamir, Nathalie

    2017-03-21

    The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with TMT labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low vs. high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism (e.g., AACS, ACOX1, ACLY) and red-ox pathways (e.g., CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response (e.g., IGTB2, IFIT3, LGALS1) and rennin angiotensin system (e.g. ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle (e.g., OTC, ARG1, CPS1), and amino acid biosynthesis (e.g., GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle (e.g., ARG1, CPS1), immune response/complement activation (e.g., C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling (e.g., EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis (e.g., YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched

  15. Anti-diabetic effect of balanced deep-sea water and its mode of action in high-fat diet induced diabetic mice.

    PubMed

    Ha, Byung Geun; Shin, Eun Ji; Park, Jung-Eun; Shon, Yun Hee

    2013-10-29

    In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500-2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.

  16. Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice

    PubMed Central

    Ha, Byung Geun; Shin, Eun Ji; Park, Jung-Eun; Shon, Yun Hee

    2013-01-01

    In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. PMID:24172214

  17. Inhibition of hippocampal long-term potentiation by high-fat diets: is it related to an effect of palmitic acid involving glycogen synthase kinase-3?

    PubMed

    Contreras, Ana; Del Rio, Danila; Martínez, Ana; Gil, Carmen; Morales, Lidia; Ruiz-Gayo, Mariano; Del Olmo, Nuria

    2017-04-12

    High-fat diets (HFD) impair hippocampal-dependent learning and memory and produce important changes in synaptic transmission by enhancing glutamate uptake, decreasing synaptic efficacy, and inhibiting plasticity mechanisms such as N-methyl-D-aspartate-mediated long-term depression (LTD) within the hippocampus. Adolescent animals seem to be particularly susceptible to the detrimental effect of HFD as dietary treatments carried out between weaning and early adulthood are much more efficient in terms of hippocampal damage that those carried out during the adult period. As palmitic acid is the most abundant saturated fatty acid in HFD, its effect on hippocampal function needs to be studied. However, glycogen synthase kinase-3 (GSK-3), a pleiotropic enzyme highly expressed in the central nervous system, modulates both hippocampal long-term potentiation (LTP) and LTD, and has been implicated in neurological disorders including Alzheimer's disease. In this study, we have characterized in mice hippocampus the effect of (i) a 48 h HFD intervention and (ii) in-vitro palmitic acid, as well as the possible involvement of GSK-3 in the above-mentioned plasticity mechanisms. Our results show that both 48 h HFD and palmitic acid inhibit LTP in hippocampal slices, whereas no effect on LTD was observed. Moreover, tideglusib, an ATP-noncompetitive inhibitor of GSK-3, induced hippocampal LTP and partially reversed the impairment of LTP induced by palmitic acid.

  18. DPP4-inhibitor improves neuronal insulin receptor function, brain mitochondrial function and cognitive function in rats with insulin resistance induced by high-fat diet consumption.

    PubMed

    Pipatpiboon, Noppamas; Pintana, Hiranya; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2013-03-01

    High-fat diet (HFD) consumption has been demonstrated to cause peripheral and neuronal insulin resistance, and brain mitochondrial dysfunction in rats. Although the dipeptidyl peptidase-4 inhibitor, vildagliptin, is known to improve peripheral insulin sensitivity, its effects on neuronal insulin resistance and brain mitochondrial dysfunction caused by a HFD are unknown. We tested the hypothesis that vildagliptin prevents neuronal insulin resistance, brain mitochondrial dysfunction, learning and memory deficit caused by HFD. Male rats were divided into two groups to receive either a HFD or normal diet (ND) for 12 weeks, after which rats in each group were fed with either vildagliptin (3 mg/kg/day) or vehicle for 21 days. The cognitive function was tested by the Morris Water Maze prior to brain removal for studying neuronal insulin receptor (IR) and brain mitochondrial function. In HFD rats, neuronal insulin resistance and brain mitochondrial dysfunction were demonstrated, with impaired learning and memory. Vildagliptin prevented neuronal insulin resistance by restoring insulin-induced long-term depression and neuronal IR phosphorylation, IRS-1 phosphorylation and Akt/PKB-ser phosphorylation. It also improved brain mitochondrial dysfunction and cognitive function. Vildagliptin effectively restored neuronal IR function, increased glucagon-like-peptide 1 levels and prevented brain mitochondrial dysfunction, thus attenuating the impaired cognitive function caused by HFD.

  19. Preventive effect of Monascus-fermented products enriched with ubiquinones on type 2 diabetic rats induced by a high-fructose plus high-fat diet.

    PubMed

    Pyo, Young-Hee; Lee, Kyung-Won

    2014-07-01

    The aim of the present study was to investigate whether the aqueous extract of Monascus-fermented grains (MFGEs) enriched with ubiquinones (Coenzyme Qs, CoQ9+CoQ10) alleviates high-fructose (60%) plus high-fat (20%) diet (HFD)-induced hyperglycemia and hepatic oxidative stress in male Sprague-Dawley rats. Animals were fed HFD for 16 weeks and orally administered with MFGEs (300 mg/kg/day) or atorvastatin (20 mg/kg/day) for the last 4 weeks of the study. HFD-fed rats exhibited hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and impaired insulin sensitivity. MFGE treatment prevented the increase in glucose levels and index of insulin resistance in the HFD-induced diabetic rats. A significant decrease in hepatic lipid peroxidation and significant increases in hepatic superoxide dismutase, catalase, and glutathione peroxidase were observed in the MFGE supplemented group. The results suggest that dietary supplementation with MFGEs enriched with CoQs exerts an antidiabetic effect in type 2 diabetic rats by improving insulin resistance and hepatic antioxidant enzymes.

  20. High-Fat Diet Augments VPAC1 Receptor-Mediated PACAP Action on the Liver, Inducing LAR Expression and Insulin Resistance

    PubMed Central

    Nakata, Masanori; Zhang, Boyang; Yang, Yifei; Okada, Takashi; Shintani, Norihito; Hashimoto, Hitoshi

    2016-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on multiple processes of glucose and energy metabolism. PACAP potentiates insulin action in adipocytes and insulin release from pancreatic β-cells, thereby enhancing glucose tolerance. Contrary to these effects at organ levels, PACAP null mice exhibit hypersensitivity to insulin. However, this apparent discrepancy remains to be solved. We aimed to clarify the mechanism underlying the antidiabetic phenotype of PACAP null mice. Feeding with high-fat diet (HFD) impaired insulin sensitivity and glucose tolerance in wild type mice, whereas these changes were prevented in PACAP null mice. HFD also impaired insulin-induced Akt phosphorylation in the liver in wild type mice, but not in PACAP null mice. Using GeneFishing method, HFD increased the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in the liver in wild type mice. Silencing of LAR restored the insulin signaling in the liver of HFD mice. Moreover, the increased LAR expression by HFD was prevented in PACAP null mice. HFD increased the expression of VPAC1 receptor (VPAC1-R), one of three PACAP receptors, in the liver of wild type mice. These data indicate that PACAP-VPAC1-R signaling induces LAR expression and insulin resistance in the liver of HFD mice. Antagonism of VPAC1-R may prevent progression of HFD-induced insulin resistance in the liver, providing a novel antidiabetic strategy. PMID:28044141

  1. Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

    PubMed Central

    Amin, Kamal A; Nagy, Mohamed A

    2009-01-01

    Background Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. Aim To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. Method White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks. Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Results Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile. Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high

  2. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  3. Meal Counting and Claiming Manual.

    ERIC Educational Resources Information Center

    Food and Nutrition Service (USDA), Washington, DC.

    This manual contains information about the selection and implementation of a meal counting and claiming system for the National School Lunch Program (NSLP) and the School Breakfast Program (BSP). Federal reimbursement is provided for each meal that meets program requirements and is served to an eligible student. Part 1 explains the six elements of…

  4. N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have demonstrated that obesity induced by high-fat diets increases bone resorption, decreases trabecular bone mass, and reduces bone strength in various animal models. This study investigated whether N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, alters glutathione statu...

  5. Preserving of Postnatal Leptin Signaling in Obesity-Resistant Lou/C Rats following a Perinatal High-Fat Diet

    PubMed Central

    Poher, Anne-Laure; Arsenijevic, Denis; Asrih, Mohamed; Dulloo, Abdul G.; Jornayvaz, François R.; Rohner-Jeanrenaud, Françoise; Veyrat-Durebex, Christelle

    2016-01-01

    Physiological processes at adulthood, such as energy metabolism and insulin sensitivity may originate before or weeks after birth. These underlie the concept of fetal and/or neonatal programming of adult diseases, which is particularly relevant in the case of obesity and type 2 diabetes. The aim of this study was to determine the impact of a perinatal high fat diet on energy metabolism and on leptin as well as insulin sensitivity, early in life and at adulthood in two strains of rats presenting different susceptibilities to diet-induced obesity. The impact of a perinatal high fat diet on glucose tolerance and diet-induced obesity was also assessed. The development of glucose intolerance and of increased fat mass was confirmed in the obesity-prone Wistar rat, even after 28 days of age. By contrast, in obesity-resistant Lou/C rats, an improved early leptin signaling may be responsible for the lack of deleterious effect of the perinatal high fat diet on glucose tolerance and increased adiposity in response to high fat diet at adulthood. Altogether, this study shows that, even if during the perinatal period adaptation to the environment appears to be genetically determined, adaptive mechanisms to nutritional challenges occurring at adulthood can still be observed in rodents. PMID:27618559

  6. Application of an in vivo hepatic triacylglycerol production method in the setting of a high fat diet in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Changes in TAG metabolism contribute to the development of hepatic steatosis including changes in production rate from de novo lipogenes...

  7. Increased circulating estradiol in mice fed a high-fat diet does not attenuate ovariectomy-induced bone structural deterioration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovariectomy-induced estrogen deficiency increases adiposity and induces substantial bone loss by increasing osteoclast activity. This study investigated whether obesity induced by a high-fat diet alter circulating estradiol levels, mitigates or exacerbates bone structure deterioration, and changes m...

  8. Time-restricted feeding of a high-fat diet reduces adiposity and inflammatory cytokine production in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disruption of the circadian rhythms contributes to obesity. Restricting feeding to particular times of the day may reset the circadian rhythms and reduce obesity and resulting complications. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity...

  9. Blueberry juice and anthocyanins modulate obesity, leptin and beta cell function in mice fed a high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anthocyanins (ACNs) are the components responsible for the red and blue colors found in many fruits and berries. Consumption of purified blueberry (BB) anthocyanins but not whole BB in the diet has been shown to prevent the development of obesity in mice fed high-fat diets (JAFC 56:647, 2008). The o...

  10. Chlorella Protein Hydrolysate Attenuates Glucose Metabolic Disorder and Fatty Liver in High-fat Diet-induced Obese Mice.

    PubMed

    Noguchi, Naoto; Yanagita, Teruyoshi; Rahman, Shaikh Mizanoor; Ando, Yotaro

    2016-07-01

    Chlorella (Parachlorella beijerinckii) powder is reported to show a preventive effect against metabolic syndromes such as arteriosclerosis, hyperlipidemia, and hypertension. Approximately 60% of the chlorella content is protein. In order to understand the role of chlorella protein, we prepared a chlorella protein hydrolysate (CPH) by protease treatment. Male C57BL/6 mice were divided into three groups: a normal diet group, high-fat diet (HFD) group, and high-fat diet supplemented with CPH (HFD+CPH) group. The CPH administration improved glucose intolerance, insulin sensitivity, and adipose tissue hypertrophy in the high-fat diet-fed mice. In addition, the HFD+CPH group had significantly decreased liver total cholesterol and triglyceride levels compared with those in the HFD group. Furthermore, the HFD+CPH group had a decreased level of monocyte chemotactic protein-1 (MCP-1) in serum and a lower MCP-1 mRNA expression level in adipose tissue compared with the HFD group. The present study suggests that chlorella protein hydrolysate can prevent a high-fat diet-induced glucose disorder and fatty liver by inhibiting adipocyte hypertrophy and reducing the MCP-1 protein and gene expression.

  11. High-fat diet enhances and plasminogen activator inhibitor-1 deficiency attenuates bone loss in mice with Lewis Lung carcinoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (PAI-1-/-) on bone structure in mice bearing Lewis lung carcinoma (LLC) in lungs. Reduction in bone volume fraction (BV/TV) by 22% and 21%, trabecular number (Tb.N) by 8% and 4% and bone mineral de...

  12. Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the effects of diet (AIN93G or high-fat), physical activity (sedentary or voluntary running) and protein source (casein or soy protein isolate) and their interactions on bone microstructural changes in distal femurs in male C57BL/6 mice by using micro-computed tomography. After 14 w...

  13. Eicosapentaenoic acid reduces high-fat diet-induced insulin resistance by altering adipose tissue glycolytic and inflammatory function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported Eicosapentaenoic Acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation. In this study, we dissected mechanisms mediating anti-inflammatory and anti-lipogenic actions of EPA, using histology/ immunohistochemistry, transcriptomi...

  14. Survival of Salmonella enterica serotype Tennessee during simulated gastric passage is improved by low water activity and high fat content.

    PubMed

    Aviles, Bryan; Klotz, Courtney; Smith, Twyla; Williams, Robert; Ponder, Monica

    2013-02-01

    The low water activity (a(w) 0.3) of peanut butter prohibits the growth of Salmonella in a product; however, illnesses are reported from peanut butter contaminated with very small doses, suggesting the food matrix itself influences the infectious dose of Salmonella, potentially by improving Salmonella's survival in the gastrointestinal tract. The purpose of our study was to quantify the survival of a peanut butter outbreak-associated strain of Salmonella enterica serotype Tennessee when inoculated into peanut butters with different fat contents and a(w) (high fat, high a(w); high fat, low a(w); low fat, high a(w); low fat, low a(w)) and then challenged with a simulated gastrointestinal system. Exposures to increased fat content and decreased a(w) both were associated with a protective effect on the survival of Salmonella Tennessee in the simulated gastric fluid compared with control cells. After a simulated intestinal phase, the populations of Salmonella Tennessee in the control and low-fat formulations were not significantly different; however, a 2-log CFU/g increase occurred in high-fat formulations. This study demonstrates that cross-protection from low-a(w) stress and the presence of high fat results in improved survival in the low pH of the stomach. The potential for interaction of food matrix and stress adaptations could influence the virulence of Salmonella and should be considered for risk analysis.

  15. High-fat diets containing different amounts of n-3 polyunsaturated acids modulate adipokine production in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dysregulation of adipokines is a hallmark of obesity. Polyunsaturated (n3) fatty acids in fish oil may exert anti-inflammatory effects on adipose tissue mitigating the dysregulation of adipokines thereby preventing obesity. This study investigated the effects of high-fat diets containing different...

  16. Resveratrol supplementation restores high-fat diet-induced insulin secretion dysfunction by increasing mitochondrial function in islet

    PubMed Central

    Kong, Wen; Zheng, Juan; Zhang, Hao-hao; Hu, Xiang; Zeng, Tian-shu; Hu, Di

    2015-01-01

    Resveratrol (RSV), a natural compound, is known for its effects on energy homeostasis. Here we investigated the effects of RSV and possible mechanism in insulin secretion of high-fat diet rats. Rats were randomly divided into three groups as follows: NC group (animals were fed ad libitum with normal chow for 8 weeks), HF group (animals were fed ad libitum with high-fat diet for 8 weeks), and HFR group (animals were treated with high-fat diet and administered with RSV for 8 weeks). Insulin secretion ability of rats was assessed by hyperglycemic clamp. Mitochondrial biogenesis genes, mitochondrial respiratory chain activities, reactive oxidative species (ROS), and several mitochondrial antioxidant enzyme activities were evaluated in islet. We found that HF group rats clearly showed low insulin secretion and mitochondrial complex dysfunction. Expression of silent mating type information regulation 2 homolog- 1 (SIRT1) and related mitochondrial biogenesis were significantly decreased. However, RSV administration group (HFR) showed a marked potentiation of glucose-stimulated insulin secretion. This effect was associated with elevated SIRT1 protein expression and antioxidant enzyme activities, resulting in increased mitochondrial respiratory chain activities and decreased ROS level. This study suggests that RSV may increase islet mitochondrial complex activities and antioxidant function to restore insulin secretion dysfunction induced by high-fat diet. PMID:25228148

  17. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  18. Hepatic Gene Expression Related to Lower Plasma Cholesterol in Hamsters Fed High Fat Diets Supplemented with Blueberry Pomace and Extract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We analyzed plasma lipid profiles, and genes related to cholesterol and bile acid metabolism, and inflammation in livers as well as adipose tissue from Syrian Golden hamsters fed high-fat diets supplemented with blueberry (BB) pomace byproducts including 8% dried whole blueberry peels (BBPWHL), 2% d...

  19. Effect of high fat diets on the NTPDase, 5'-nucleotidase and acetylcholinesterase activities in the central nervous system.

    PubMed

    Kaizer, Rosilene Rodrigues; Spanevello, Rosélia Maria; Costa, Eduarda; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2017-03-01

    High fat diets are associated with the promotion of neurological diseases, such as Alzheimer disease (AD). This study aim investigate the high fat diets role to promotion of AD using as biochemistry parameter of status of central nervous system through the NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in brain of young rats. The intake of high fat diets promotes an inhibition of purinergic and cholinergic functions, mainly in the long-term exposure to saturated and saturated/unsaturated diets. The AChE activity was decreased to supernatant and synaptosomes tissues preparations obtained from cerebral cortex in average of 20%, to both groups exposed to saturated and saturated/unsaturated diets, when compared to the control group. Very similar results were found in hippocampus and cerebellum brain areas. At same time, the adenine nucleotides hydrolysis in synaptosomes of cerebral cortex were decreased to ATP, ADP and AMP after the long-term exposure to high fat diets, as saturated and saturated/unsaturated. The inhibition of ATP hydrolysis was of 26% and 39% to saturated and saturated/unsaturated diets, respectively. ADP hydrolysis was decreased in 20% to saturated diet, and AMP hydrolysis was decreased in 25% and 33% to saturated and saturated/unsaturated diets, respectively, all in comparison to the control. Thus, we can suggest that the effects of high diets on the purinergic and cholinergic nervous system may contribute to accelerate the progressive memory loss, to decline in language and other cognitive disruptions, such as AD patients presents.

  20. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High-Fat Diets

    PubMed Central

    Lindenmaier, Laurence B.; Philbrick, Kenneth A.; Branscum, Adam J.; Kalra, Satya P.; Turner, Russell T.; Iwaniec, Urszula T.

    2016-01-01

    Low bone mass is often associated with elevated bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell (MSC) progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Leptin deficiency and high-fat diet-induced obesity are associated with increased marrow adipose tissue (MAT) and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice following recombinant adeno-associated virus (rAAV) gene therapy. Eight- to 10-week-old male ob/ob mice were randomized into four groups: (1) untreated, (2) rAAV-Lep, (3) rAAV-green fluorescent protein (rAAV-GFP), or (4) pair-fed to rAAV-Lep. For vector administration, mice were injected intracerebroventricularly with either rAAV-leptin gene therapy (rAAV-Lep) or rAAV-GFP (9 × 107 particles) and maintained for 30 weeks. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high-fat diets; ob/ob mice were randomized into two groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high-fat diet for 8 weeks. Wild-type (WT) controls included age-matched mice fed regular or high-fat diet. High-fat diet resulted in a threefold increase in MAT in WT mice, whereas MAT was increased by leptin deficiency up to 50-fold. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high-fat diet to values similar to WT mice fed regular diet. These findings suggest

  1. High Fat Diet Induces Adhesion of Platelets to Endothelium in Two Models of Dyslipidemia

    PubMed Central

    Gonzalez, Jaime; Donoso, Wendy; Díaz, Natalia; Albornoz, María Eliana; Huilcaman, Ricardo; Morales, Erik

    2014-01-01

    Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/− mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/− mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cells in vivo. These findings support studying the participation of platelets in the formation of atheromatous plate. PMID:25328689

  2. Effect of Lactobacillus plantarum Strain K21 on High-Fat Diet-Fed Obese Mice.

    PubMed

    Wu, Chien-Chen; Weng, Wei-Lien; Lai, Wen-Lin; Tsai, Hui-Ping; Liu, Wei-Hsien; Lee, Meng-Hwan; Tsai, Ying-Chieh

    2015-01-01

    Recent studies have demonstrated beneficial effects of specific probiotics on alleviating obesity-related disorders. Here we aimed to identify probiotics with potential antiobesity activity among 88 lactic acid bacterial strains via in vitro screening assays, and a Lactobacillus plantarum strain K21 was found to harbor abilities required for hydrolyzing bile salt, reducing cholesterol, and inhibiting the accumulation of lipid in 3T3-L1 preadipocytes. Furthermore, effects of K21 on diet-induced obese (DIO) mice were examined. Male C57Bl/6J mice received a normal diet, high-fat diet (HFD), or HFD with K21 administration (10(9) CFU in 0.2 mL PBS/day) for eight weeks. Supplementation of K21, but not placebo, appeared to alleviate body weight gain and epididymal fat mass accumulation, reduce plasma leptin levels, decrease cholesterol and triglyceride levels, and mitigate liver damage in DIO mice. Moreover, the hepatic expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) related to adipogenesis was significantly downregulated in DIO mice by K21 intervention. We also found that K21 supplementation strengthens intestinal permeability and modulates the amount of Lactobacillus spp., Bifidobacterium spp., and Clostridium perfringens in the cecal contents of DIO mice. In conclusion, our results suggest that dietary intake of K21 protects against the onset of HFD-induced obesity through multiple mechanisms of action.

  3. Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice

    PubMed Central

    Soni, Nikul K.; Ross, Alastair B.; Scheers, Nathalie; Savolainen, Otto I; Nookaew, Intawat; Gabrielsson, Britt G.; Sandberg, Ann-Sofie

    2016-01-01

    Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation. PMID:27598198

  4. Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

    PubMed

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-05-09

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

  5. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    PubMed Central

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  6. Fermented garlic protects diabetic, obese mice when fed a high-fat diet by antioxidant effects.

    PubMed

    Jung, Young-Mi; Lee, Seon-Ha; Lee, Dong-Sub; You, Myung-Jin; Chung, In Kwon; Cheon, Woo Hyun; Kwon, Young-Sam; Lee, Young-Joon; Ku, Sae-Kwang

    2011-05-01

    This study examined the bioactivity of yeast (Saccharomyces cerevisiae)-fermented aged black garlic (FBG) on obese mice supplied a high-fat diet (HFD) and its in vitro antioxidant activity. Aged black garlic (BG) exhibits potent antioxidative effects and has been subjected to extensive research. In addition, the bioactivity of some natural products is increased by fermentation. In a preliminary test, this study found that the antioxidant activity of FBG is stronger than that of BG. Therefore, it was hypothesized that the bioactivity of BG would be increased by yeast fermentation and would be a good candidate as a nutraceutical product for improving the oxidative defense systems in older patients or patients affected by various oxidative stresses, for example, diabetes and diabetic complications. To test this hypothesis, the bioactivities of FBG in diabetic and obese mice as well as the antioxidant activity in vitro were examined. After 91 days of continuous HFD supply, the mice showed marked obesity, hyperglycemia, hyperlipemia, and liver and kidney damages. Black garlic and all 3 different doses of FBG showed favorable hepatoprotective, nephroprotective, hypolipidemic, and antiobesity effects compared with the HFD control, but no hypoglycemic effects. In particular, more favorable bioactivity against all 4 HFD-induced diabetic complications was detected in the FBG-treated groups compared with the group given equivalent doses of BG. These findings suggest that the bioactivities of BG can be improved by yeast fermentation.

  7. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice

    PubMed Central

    Dinh, Chi H. L.; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

    2016-01-01

    Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora. PMID:26920068

  8. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.

    PubMed

    Dinh, Chi H L; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

    2016-04-01

    Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.

  9. Glucocorticoids induced high fat diet preference via activating hypothalamic AMPK signaling in chicks.

    PubMed

    Liu, Lei; Wang, Xiaojuan; Jiao, Hongchao; Lin, Hai

    2017-03-02

    Glucocorticoids (GCs) stimulate appetite, contributing to enhanced fat deposition. Our present study was conducted to determine whether GCs could evoke an appetite specifically for fat-rich diets in chicks. Chicks were subjected to a subcutaneous injection of corticosterone (CORT, 2mg/kg body weight/day) or corn oil (control), and food preference was tested. The results showed that CORT-chicks consumed more high-fat diet (HFD) compared with controls. In HFD-fed chicks, hypothalamic phosphorylated AMP-activated protein kinase α (AMPKα) and neuropeptide Y (NPY) mRNA levels were increased by CORT treatment. Activating AMPK with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, an AMPK activator, via intracerebroventricular injection further enhanced the CORT-induced HFD consumption and concurrently up-regulated NPY mRNA levels and phosphorylated AMPKα and acetyl-coenzyme A carboxylase levels. The dramatic increase in HFD consumption and upregulation of NPY mRNA levels and phospho-AMPKα levels induced by peripheral CORT injection was not altered by intracerebroventricular infusion of compound C (4-16μg), an AMPK inhibitor. In conclusion, CORT challenge caused a HFD preference by enhancing the AMPK pathway in the hypothalamus.

  10. Simultaneous introduction of a novel high fat diet and wheel running induces anorexia.

    PubMed

    Scarpace, E T; Matheny, M; Strehler, K Y E; Shapiro, A; Cheng, K Y; Tümer, N; Scarpace, P J

    2012-02-28

    Voluntary wheel running (WR) is a form of physical activity in rodents that influences ingestive behavior. The present report describes an anorexic behavior triggered by the simultaneous introduction of a novel diet and WR. This study examined the sequential, compared with the simultaneous, introduction of a novel high-fat (HF) diet and voluntary WR in rats of three different ages and revealed a surprising finding; the simultaneous introduction of HF food and voluntary WR induced a behavior in which the animals chose not to eat although food was available at all times. This phenomenon was apparently not due to an aversion to the novel HF diet because introduction of the running wheels plus the HF diet, while continuing the availability of the normal chow diet did not prevent the anorexia. Moreover, the anorexia was prevented with prior exposure to the HF diet. In addition, the anorexia was not related to extent of WR but dependent on the act of WR. The introduction a HF diet and locked running wheels did not induce the anorexia. This voluntary anorexia was accompanied by substantial weight loss, and the anorexia was rapidly reversed by removal of the running wheels. Moreover, the HF/WR-induced anorexia is preserved across the age span despite the intrinsic decrease in WR activity and increased consumption of HF food with advancing age. The described phenomenon provides a new model to investigate anorexia behavior in rodents.

  11. Resveratrol potentiates rapamycin to prevent hyperinsulinemia and obesity in male mice on high fat diet

    PubMed Central

    Leontieva, O V; Paszkiewicz, G; Demidenko, Z N; Blagosklonny, M V

    2013-01-01

    High doses of rapamycin, an antiaging agent, can prevent obesity in mice on high fat diet (HFD). Obesity is usually associated with hyperinsulinemia. Here, we showed that rapamycin given orally, at doses that did not affect weight gain in male mice on HFD, tended to decrease fasting insulin levels. Addition of resveratrol, which alone did not affect insulin levels, potentiated the effect of rapamycin, so that the combination decreased obesity and prevented hyperinsulinemia. Neither rapamycin nor resveratrol, and their combination affected fasting levels of glucose (despite lowering insulin levels), implying that the combination might prevent insulin resistance. We and others previously reported that resveratrol at high doses inhibited the mTOR (Target of Rapamycin) pathway in cell culture. Yet, as we confirmed here, this effect was observed only at super-pharmacological concentrations. At pharmacological concentrations, resveratrol did not exert ‘rapamycin-like effects' on cellular senescence and did not inhibit the mTOR pathway in vitro, indicating nonoverlapping therapeutic mechanisms of actions of rapamycin and resveratrol in vivo. Although, like rapamycin, resveratrol decreased insulin-induced HIF-1-dependent transcription in cell culture, resveratrol did not inhibit mTOR at the same concentrations. Given distinct mechanisms of action of rapamycin and resveratrol at clinically relevant doses, their combination warrants further investigation as a potential antiaging, antiobesity and antidiabetic modality. PMID:23348586

  12. Maternal high-fat diet prevents developmental programming by early-life stress

    PubMed Central

    Rincel, M; Lépinay, A L; Delage, P; Fioramonti, J; Théodorou, V S; Layé, S; Darnaudéry, M

    2016-01-01

    Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development. PMID:27898075

  13. One-year high fat diet affects muscle-but not brain mitochondria.

    PubMed

    Jørgensen, Tenna; Grunnet, Niels; Quistorff, Bjørn

    2015-06-01

    It is well known that few weeks of high fat (HF) diet may induce metabolic disturbances and mitochondrial dysfunction in skeletal muscle. However, little is known about the effects of long-term HF exposure and effects on brain mitochondria are unknown. Wistar rats were fed either chow (13E% fat) or HF diet (60E% fat) for 1 year. The HF animals developed obesity, dyslipidemia, insulin resistance, and dysfunction of isolated skeletal muscle mitochondria: state 3 and state 4 were 30% to 50% increased (P<0.058) with palmitoyl carnitine (PC), while there was no effect with pyruvate as substrate. Adding also succinate in state 3 resulted in a higher substrate control ratio (SCR) with PC, but a lower SCR with pyruvate (P<0.05). The P/O2 ratio was lower with PC (P<0.004). However, similar tests on isolated brain mitochondria from the same animal showed no changes with the substrates relevant for brain (pyruvate and 3-hydroxybutyrate). Thus, long-term HF diet was associated with obesity, dyslipidemia, insulin resistance, and significantly altered mitochondrial function in skeletal muscle. Yet, brain mitochondria were unaffected. We suggest that the relative isolation of the brain due to the blood-brain barrier may play a role in this strikingly different phenotype of mitochondria from the two tissues of the same animal.

  14. High fat diet drives obesity regardless the composition of gut microbiota in mice

    PubMed Central

    Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L.; Chou, Chieh Jason

    2016-01-01

    The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1st week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice. PMID:27577172

  15. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus

    PubMed Central

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  16. Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals’ access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID:27189661

  17. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice<