Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)

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Abstract 480: Exacerbation of Arterial Stiffness in Obese Adiponectin Deficient Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.480 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Megha Murali ◽

Carla Taylor ◽

Peter Zahradka ◽

Jeffrey Wigle

Keyword(s):

Arterial Stiffness ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

High Fat Diet ◽

Pulse Wave ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

High Fat Diets ◽

Fat Diets

Background and Objective: Arterial stiffness is recognized as being an independent predictor of incipient vascular disease associated with obesity and metabolic syndrome. In obese subjects, the decrease in the plasma level of adiponectin, an anti-diabetic and anti-atherogenic adipokine, is well known. Hence the aim of our study was to examine the effect of loss of adiponectin on the development of arterial stiffness in response to a high fat diet. Methods and Results: Male 8-week old adiponectin knockout (APN KO) and C57BL/6 (control) mice were fed a high fat diet (60% Calories from fat) for 12 weeks to induce obesity and insulin resistance (n=10/group). APN KO and C57BL/6 mice were fed a low fat diet (10% Calories from fat) and used as lean controls (n=10/group). After 12 weeks on the high fat diet, the APN KO mice weighed significantly more than the C57BL/6 mice (45.1±1.3 g vs 40.1±1.1 g, p=0.0008) but there was no difference in the final weights between genotypes fed the low fat diet. APN KO mice on both high and low fat diets for 12 weeks developed insulin resistance as measured by oral glucose tolerance test (Area under curve (AUC) mmol/L х min = 437±70 and 438±57) as compared to the C57BL/6 mice fed low or high fat diets (AUC mmol/L х min = 251±27 and 245±43). Arterial stiffness was determined by Doppler pulse wave velocity analysis of the femoral artery. Pulse wave velocity was increased in APN KO mice fed a high fat diet relative to those fed the low fat diet (12.56±0.78 cm/s vs 9.47±0.95 cm/s, p=0.0035; n=8-10). Pulse wave velocity was not different between C57BL/6 control mice on the low or high fat diets (10.63±0.73 cm/s and 10.86±0.50 cm/s), thus revealing that only mice deficient in adiponectin developed arterial stiffness in response to high fat diet. Conclusions: Potentiation of the vascular stiffness in diet-induced obese APN KO mice indicates that adiponectin has a role in modulating vascular structure and the APN KO mouse models the vascular changes that occur in human obesity and metabolic disorders. Morphometric analysis of the aortic tissues for vessel thickness and expression of extracellular proteins will further validate the potential role of adiponectin on the maintenance of arterial elasticity in addition to its known effect on eNOS mediated vasoprotection.

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Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.1.r279 ◽

1999 ◽

Vol 277 (1) ◽

pp. R279-R285 ◽

Cited By ~ 20

Author(s):

Mihai Covasa ◽

Robert C. Ritter

Keyword(s):

Oleic Acid ◽

Food Intake ◽

High Fat Diet ◽

High Fat ◽

Low Fat ◽

Satiation Effect ◽

Low Fat Diet ◽

High Fat Diets ◽

Intestinal Infusion ◽

Fat Diets

When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens.

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High-fat diet changes the temporal profile of GLP-1 receptor-mediated hypophagia in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00588.2012 ◽

2013 ◽

Vol 305 (1) ◽

pp. R68-R77 ◽

Cited By ~ 20

Author(s):

Joram D. Mul ◽

Denovan P. Begg ◽

Jason G. Barrera ◽

Bailing Li ◽

Emily K. Matter ◽

...

Keyword(s):

Food Intake ◽

High Fat Diet ◽

Reduce Food Intake ◽

High Fat ◽

Low Fat ◽

Temporal Profile ◽

Low Fat Diet ◽

High Fat Diets ◽

Glucagon Like Peptide 1 ◽

Fat Diets

Overconsumption of a high-fat diet promotes weight gain that can result in obesity and associated comorbidities, including Type 2 diabetes mellitus. Consumption of a high-fat diet also alters gut-brain communication. Glucagon-like peptide 1 (GLP-1) is an important gastrointestinal signal that modulates both short- and long-term energy balance and is integral in maintenance of glucose homeostasis. In the current study, we investigated whether high-fat diets (40% or 81% kcal from fat) modulated the ability of the GLP-1 receptor (GLP-1r) agonists exendin-4 (Ex4) and liraglutide to reduce food intake and body weight. We observed that rats maintained on high-fat diets had a delayed acute anorexic response to peripheral administration of Ex4 or liraglutide compared with low-fat diet-fed rats (17% kcal from fat). However, once suppression of food intake in response to Ex4 or liraglutide started, the effect persisted for a longer time in the high-fat diet-fed rats compared with low-fat diet-fed rats. In contrast, centrally administered Ex4 suppressed food intake similarly between high-fat diet-fed and low-fat diet-fed rats. Chronic consumption of a high-fat diet did not change the pharmacokinetics of Ex4 but increased intestinal Glp1r expression and decreased hindbrain Glp1r expression. Taken together, these findings demonstrate that dietary composition alters the temporal profile of the anorectic response to exogenous GLP-1r agonists.

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Three Weeks on a High-Fat Diet Increases Intrahepatic Lipid Accumulation and Decreases Metabolic Flexibility in Healthy Overweight Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2243 ◽

2011 ◽

Vol 96 (4) ◽

pp. E691-E695 ◽

Cited By ~ 74

Author(s):

Noud A. van Herpen ◽

Vera B. Schrauwen-Hinderling ◽

Gert Schaart ◽

Ronald P. Mensink ◽

Patrick Schrauwen

Keyword(s):

Insulin Sensitivity ◽

High Fat Diet ◽

Respiratory Quotient ◽

Resonance Spectroscopy ◽

Metabolic Flexibility ◽

High Fat ◽

Low Fat ◽

High Fat Diets ◽

Fat Diets ◽

Intrahepatic Lipid

Abstract Context: In rodents, high-fat diets increase intrahepatic lipid (IHL), but human studies are scarce. Objective: Our objective was to examine whether high-fat diets influence IHL, intramyocellular lipids (IMCL), and insulin resistance. Design: Twenty overweight men were randomly allocated to low- or high-fat groups (age, 54.0 ± 2.3 and 56.4 ± 2.5 yr; body mass index, 29.3 ± 0.6 and 28.3 ± 0.5 kg/m2, respectively). Both groups started with a 3-wk low-fat diet [15% energy (En%) as protein, 65 En% as carbohydrates, 20 En% as fat], after which half of the subjects switched to a 3-wk isocaloric high-fat diet (15 En% protein, 30 En% carbohydrates, 55 En% fat). After 3 and 6 wk, IHL and IMCL content were assessed by 1H magnetic resonance spectroscopy and a muscle biopsy, and insulin sensitivity was studied using a hyperinsulinemic-euglycemic clamp. An additional liver scan was performed after 1 wk in the high-fat group. Results: IHL decreased by 13% in the low-fat group and increased by 17% in high-fat group (P = 0.047). IMCL content was unaffected (P = 0.304). Insulin sensitivity was unaffected. At wk 3, IHL correlated negatively with insulin sensitivity (r = −0.584; P = 0.009, all subjects combined). Metabolic flexibility, defined as change in respiratory quotient upon insulin stimulation, was decreased after 3 wk of the high-fat diet (change in respiratory quotient was +0.02 ± 0.02 vs. −0.05 ± 0.1 in low-fat vs. high-fat group, P = 0.009). Basal plasma glucose increased after the high-fat diet (P = 0.038). Plasma parameters insulin, free fatty acids, high-sensitivity C-reactive protein, and liver enzymes and body weight were unaffected by diet. Conclusion: A 3-wk high-fat diet leads to IHL accumulation and a decreased metabolic flexibility, but insulin sensitivity is unaffected.

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Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642518 ◽

1994 ◽

Vol 71 (06) ◽

pp. 755-758 ◽

Cited By ~ 46

Author(s):

E M Bladbjerg ◽

P Marckmann ◽

B Sandström ◽

J Jespersen

Keyword(s):

High Fat Diet ◽

Fat Content ◽

Factor Vii ◽

Amidolytic Activity ◽

High Fat ◽

Low Fat Diet ◽

Increased Risk ◽

Coagulant Activity ◽

High Fat Diets ◽

Fat Diets

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.

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Dietary Folic Acid and Fat Alter Metabolism of Multiple Vitamins in Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzaa067_005 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1778-1778

Author(s):

Keri Barron ◽

Natalia Krupenko

Keyword(s):

Folic Acid ◽

Vitamin A ◽

Metabolic Pathways ◽

Vitamin B6 ◽

High Fat ◽

Low Fat ◽

Funding Sources ◽

Low Fat Diet ◽

High Fat Diets ◽

Fat Diets

Abstract Objectives To determine how low and high folic acid (FA) intake, combined with either low or high-fat diets, affects other vitamins in mouse liver and plasma. Methods C57BL/6NHsd mice were placed on one of six diets at weaning and maintained for 16 weeks. The diets varied in their fat content and FA levels: low fat (14% kcal from fat) vs high fat (58% kcal from fat) with 3 different FA levels- 0 ppm FA (FD), 2 ppm FA (Ctrl), 12 ppm (FS). Diets were matched for all other vitamins and minerals. Untargeted metabolomics analysis of plasma and snap-frozen liver samples was conducted at Metabolon®. Results In liver, excess dietary folic acid on a low-fat diet resulted in significantly increased levels of pantothenate, α-tocopherol, FA and several folate metabolites. When FA was over-supplemented in combination with a high fat (HF) diet, α-tocopherol was increased along with several nicotinate and pantothenate metabolites. Interestingly, the HF-FD and -FS diets demonstrated similar effects. These diets resulted in significantly decreased levels of riboflavin, thiamine, vitamin A, and vitamin B6 metabolites while increasing levels of pantetheine metabolites. In plasma, fewer changes with significant differences were observed when mice were fed HF diets. Several nicotinate metabolites were significantly elevated due to the FD diet with no change due to FS. Additionally, there were no changes in pantothenate or riboflavin in the plasma. Interestingly, the HF- FD and -FS diets induced similar responses but in opposite directions in plasma vs liver. The plasma levels of thiamine, vitamin A, and vitamin B6 metabolites were all significantly increased due to both low and high FA, whereas in the liver they were decreased. Additionally, no changes in α-tocopherol were seen in plasma, but the HF-FD diet raised γ/β-tocopherol levels over 2-fold despite equal amounts of vitamin E among all diets. Conclusions Untargeted metabolomic analysis revealed that diets with too high or too low folate affect other vitamins both in liver and plasma. These effects were further modulated by dietary fat levels. The HF-FD and -FS diets had significant impact on vitamins A, B1, B2, B3, B5, B6, B9 and E, along with their related derivatives, which may have serious implications for multiple metabolic pathways. Funding Sources NIH.

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Metabolic Flexibility: Interplay of Diet Composition and Intermittent Fasting on Healthspan (P08-053-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-053-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Sarah Wong ◽

Rafael de Cabo ◽

Michel Bernier ◽

Alberto Diaz-Ruiz ◽

Tyler Rhinesmith ◽

...

Keyword(s):

Insulin Sensitivity ◽

High Fat Diet ◽

Diet Composition ◽

Intermittent Fasting ◽

Metabolic Flexibility ◽

Standard Diet ◽

High Fat ◽

High Fat Diets ◽

Ad Libitum ◽

Fat Diets

Abstract Objectives 4:10 periodic fasting schedule is proposed to improve biomarkers of healthspan through metabolic flexibility in mice on both standard and high fat diets. Methods Our study adopted the 4:10 fasting schedule using the fasting-mimicking diet (FMD) as our model. FMD is a plant-based, low-protein, and low-sugar diet regime implemented for four days every two-week cycle. Its regenerative effect is observed in the refeeding phase following starvation, allowing for the breakdown of cells via increased autophagy. In comparison to stricter fasting regimes such as intermittent fasting, chronic caloric restriction, and periodic fasting, FMD is well-tolerated in the clinical setting. 74 12-month old C57BL/6 mice were randomized into two diet groups: standard diet or high-fat diet. For 4 days out of every fourteen days, the mice were severely caloric restricted and refed with ad-libitum of either standard or high fat diets for the remaining 10 days, matching the controls who were fixed on the ad-libitum diet. The 4:10 fasting schedule was repeated 11 times before the mice were sacrificed. To measure metabolic flexibility, metabolic cages, ELISA, and glucose meters were used. Results Body weight and composition, metabolic flexibility, and insulin sensitivity indicate differences between fasting on diet composition. Not only did those on the fasting high-fat diet (FHFD) remain overweight, identical to their HFD controls, insulin sensitivity was also attenuated in FHFD groups. Fasting standard diet (FSD) had a reduction of 5% in body weight and 15% in body fat. Carbohydrate and lipid metabolism differences indicated by the respiratory exchange ratio as well as motor function performance differences further support the positive impact of fasting on SD groups, not HFD groups. Characteristic of positive healthspan biomarkers, reduced leptin and improved insulin sensitivity was observed with FSD, not FHFD. Conclusions We found that while the FMD schedule improved healthspan as indicated by biomarkers of healthy aging for mice on the standard diet, it could not counteract the negative health effects of the obesogenic diet. These results demonstrate the importance of not only time of feeding but also diet composition in respect to healthspan. Funding Sources National Institute on Aging (NIA) – National Institutes of Health (NIH).

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Intramyocellular lipid content is lower with a low-fat diet than with high-fat diets, but that may not be relevant for health

American Journal of Clinical Nutrition ◽

10.1093/ajcn/86.5.1316 ◽

2007 ◽

Vol 86 (5) ◽

pp. 1316-1322 ◽

Cited By ~ 6

Author(s):

Marie-Pierre St-Onge ◽

Bradley R Newcomer ◽

Steven Buchthal ◽

Inmaculada Aban ◽

David B Allison ◽

...

Keyword(s):

Lipid Content ◽

Intramyocellular Lipid ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

High Fat Diets ◽

Fat Diets ◽

Intramyocellular Lipid Content

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Corn starch dextrin changes intestinal microbiota and its metabolic activity in rats fed a basal and high-fat diet

British Food Journal ◽

10.1108/bfj-02-2019-0083 ◽

2019 ◽

Vol 121 (9) ◽

pp. 2219-2232 ◽

Cited By ~ 2

Author(s):

Renata Barczynska ◽

Adam Jurgoński ◽

Katarzyna Slizewska ◽

Jerzy Juśkiewicz ◽

Janusz Kapusniak

Keyword(s):

Intestinal Microbiota ◽

High Fat Diet ◽

Corn Starch ◽

Enteric Bacteria ◽

High Fat ◽

Low Fat ◽

Content Type ◽

High Fat Diets ◽

Fat Diets

Purpose The purpose of this paper is to determine the influence of low-fat and high-fat diets supplemented with dextrin obtained from corn starch on the numbers and relative proportions of enteric bacteria Bacteroidetes (Bacteroides, Prevotella), Actinobacteria (Bifidobacterium) and Firmicutes (Clostridium, Lactobacillus). Moreover, basic indicators of gastrointestinal function (among other things: epidydymal fat mass, mass with contents, pH in the colon, cecum, small intestine, fecal enzymes were investigation) and short-chain fatty acids are analyzed. Design/methodology/approach In vivo experimental studies in rats (analized samples of the ileal, cecal and colonic digesta; pH; blood serum; fecal enzymes); determination of the number of bacteria – fluorescence in situ hybridization; and determination of type and concentration SCFA – HPLC were considered. Findings No statistically significant differences in final body weight were found between rats fed low-fat and high-fat diets supplemented with dextrin. In rats fed the low-fat diet with dextrin, the gut microbiota composition was as follows: 42.74 percent Bacteroises and Prevotella (Bacteroidetes), 35.28 percent Clostridium and Lactobacilllus (Firmicutes) and 21.98 percent Bifidobacterium (Actinobacteria), while in rats fed the high-fat diet with dextrin it was similar. Irrespective of the diet type, supplementation with dextrin enhances bacterial glycolytic activity and the cecal production of total SCFAs, with strongly increased propionate and decreased butyrate fermentation. Practical implications Dextrin may enrich food or be a component of functional foods. Originality/value Dextrin from corn starch may contribute to changes in the composition of intestinal microbiota.

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