scholarly journals Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2523
Author(s):  
Josephine Skat-Rørdam ◽  
David Højland Ipsen ◽  
Patrick Duncan Hardam ◽  
Markus Latta ◽  
Jens Lykkesfeldt ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Control Diet ◽  
Treatment Modalities ◽  
High Fat ◽  
Low Fat ◽  
Alcoholic Fatty Liver ◽  
Sugar Water ◽  
High Starch ◽  
Dietary Components ◽  
Disease Stages

Pharmacological treatment modalities for non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are scarce, and discoveries are challenged by lack of predictive animal models adequately reflecting severe human disease stages and co-morbidities such as obesity and type 2 diabetes. To mimic human NAFLD/NASH etiology, many preclinical models rely on specific dietary components, though metabolism may differ considerably between species, potentially affecting outcomes and limiting comparability between studies. Consequently, understanding the physiological effects of dietary components is critical for high translational validity. This study investigated the effects of high fat, cholesterol, and carbohydrate sources on NASH development and metabolic outcomes in guinea pigs. Diet groups (n = 8/group) included: low-fat low-starch (LF-LSt), low-fat high-starch (LF-HSt), high-fat (HF) or HF with 4.2%, or 8.4% sugar water supplementation. The results showed that caloric compensation in HF animals supplied with sugar water led to reduced feed intake and a milder NASH phenotype compared to HF. The HF group displayed advanced NASH, weight gain and glucose intolerance compared to LF-LSt animals, but not LF-HSt, indicating an undesirable effect of starch in the control diet. Our findings support the HF guinea pig as a model of advanced NASH and highlights the importance in considering carbohydrate sources in preclinical studies of NAFLD.

scholarly journals Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity

2020 ◽  
Vol 96 (6) ◽  
Author(s):  
Sarah L Becker ◽  
Edna Chiang ◽  
Anna Plantinga ◽  
Hannah V Carey ◽  
Garret Suen ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
High Fat ◽  
Low Fat ◽  
Treatment Groups ◽  
Low Fat Diet ◽  
Taxonomic Groups ◽  
Induced Changes

ABSTRACT Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.

Control diet in a high-fat diet study in mice: Regular chow and purified low-fat diet have similar effects on phenotypic, metabolic, and behavioral outcomes

2017 ◽  
Vol 22 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Camila P. Almeida-Suhett ◽  
Jonathan M. Scott ◽  
Alice Graham ◽  
Yifan Chen ◽  
Patricia A. Deuster
Keyword(s):  
High Fat Diet ◽  
Control Diet ◽  
Behavioral Outcomes ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Diet Study

scholarly journals High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo

2008 ◽  
Vol 417 (1) ◽  
pp. 183-193 ◽  
Author(s):  
Sudheer K. Mantena ◽  
Denty Paul Vaughn ◽  
Kelly K. Andringa ◽  
Heather B. Eccleston ◽  
Adrienne L. King ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
High Fat Diet ◽  
Protein Modification ◽  
Control Diet ◽  
Critical Role ◽  
Liver Mitochondria ◽  
Mitochondrial Proteins ◽  
High Fat ◽  
Alcoholic Fatty Liver

NAFLD (non-alcoholic fatty liver disease), associated with obesity and the cardiometabolic syndrome, is an important medical problem affecting up to 20% of western populations. Evidence indicates that mitochondrial dysfunction plays a critical role in NAFLD initiation and progression to the more serious condition of NASH (non-alcoholic steatohepatitis). Herein we hypothesize that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species). To test this concept, C57BL/6 mice were pair-fed a control diet and HFD containing 35% and 71% total calories (1 cal≈4.184 J) from fat respectively, for 8 or 16 weeks and liver hypoxia, mitochondrial bioenergetics, NO (nitric oxide)-dependent control of respiration, and 3-NT (3-nitrotyrosine), a marker of protein modification by RNS, were examined. Feeding a HFD for 16 weeks induced NASH-like pathology accompanied by elevated triacylglycerols, increased CYP2E1 (cytochrome P450 2E1) and iNOS (inducible nitric oxide synthase) protein, and significantly enhanced hypoxia in the pericentral region of the liver. Mitochondria from the HFD group showed increased sensitivity to NO-dependent inhibition of respiration compared with controls. In addition, accumulation of 3-NT paralleled the hypoxia gradient in vivo and 3-NT levels were increased in mitochondrial proteins. Liver mitochondria from mice fed the HFD for 16 weeks exhibited depressed state 3 respiration, uncoupled respiration, cytochrome c oxidase activity, and mitochondrial membrane potential. These findings indicate that chronic exposure to a HFD negatively affects the bioenergetics of liver mitochondria and this probably contributes to hypoxic stress and deleterious NO-dependent modification of mitochondrial proteins.

scholarly journals Role of sex and high fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease

2020 ◽  
Author(s):  
Lisa. S. Robison ◽  
Olivia J. Gannon ◽  
Melissa A. Thomas ◽  
Abigail E. Salinero ◽  
Charly Abi-Ghanem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mouse Model ◽  
Glucose Intolerance ◽  
Systemic Inflammation ◽  
Fat Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Increased Risk ◽  
Ad Mouse Model

AbstractHypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observable years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high fat diet and metabolic disease (e.g. obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex. WT and 3xTg-AD male and female mice were fed a control (10% fat) or high fat (HF; 60% diet) diet from ~3-7 months of age, then tested for metabolic and hypothalamic disturbances. On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group. These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.

Insufficient islet compensation to insulin resistance vs. reduced glucose effectiveness in glucose-intolerant mice

2002 ◽  
Vol 283 (4) ◽  
pp. E738-E744 ◽  
Author(s):  
Bo Ahrén ◽  
Giovanni Pacini
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Control Diet ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
High Fat ◽  
Intravenous Glucose ◽  
Glucose Effectiveness ◽  
Time Points

This study evaluated the relative contribution of insulin-dependent mechanisms vs. mechanisms independent on dynamic insulin for glucose intolerance induced by high-fat diet. C57BL/6J mice underwent a frequently sampled intravenous glucose tolerance test (1 g/kg glucose) at 1 wk and 1, 3, and 10 mo after initiation of a high-fat diet (58% fat; control diet 11% fat) to measure glucose effectiveness (SG) and disposition index (DI), i.e., insulin sensitivity (SI) times early or total insulin secretion. Glucose disappearance (KG) and SI were reduced in high-fat-fed mice at all time points. Total (50 min) insulin secretion was sufficiently increased at all time points to compensate for the reduced SI, as judged by normal DI50 min. In contrast, early (10 min) insulin secretion was not sufficiently increased; DI10 min was reduced after 1, 3, and 10 mo. SG was reduced after 1 wk; the reduction persisted throughout the study period. Thus glucose intolerance induced by high-fat diet is, in early phases, solely explained by reduced glucose effectiveness, whereas insufficient early insulin secretion is of importance after long-term feeding.

Beneficial effects of maternal swimming during pregnancy on offspring metabolism when the father is obese

2018 ◽  
Vol 10 (4) ◽  
pp. 502-506 ◽  
Author(s):  
R. Tarevnic ◽  
F. Ornellas ◽  
C. A. Mandarim-de-Lacerda ◽  
M. B. Aguila
Keyword(s):  
Body Size ◽  
Exercise Training ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Beneficial Effects ◽  
Maternal Exercise ◽  
The Impact ◽  
Old Mice

AbstractWe aimed to evaluate the impact of maternal exercise training on the offspring metabolism and body size caused by father obesity. C57BL/6 male 4-week-old mice were fed a high-fat diet (HF father) or control diet (C father), while equal age female mice were fed only a C diet and were separated into two groups: trained (T mother) and non-trained (NT mother), and at 12 weeks of age mice were mated. A continuous swimming protocol was applied for 10 weeks (before and during gestation), and offspring were followed since weaning until sacrifice (at 12 weeks of age). HF father, compared to C father, showed obesity, elevated total cholesterol (TC) and triglycerides (TG), and glucose intolerance. Both sexes HF/NT offspring showed hyperglycemia, glucose intolerance and high levels of TC and TG, without obesity. However, HF/T offspring showed data close to C/NT, demonstrating the beneficial effect of maternal exercise in the offspring of obese fathers.

scholarly journals n-3 PUFA prevent metabolic disturbances associated with obesity and improve endothelial function in golden Syrian hamsters fed with a high-fat diet

2011 ◽  
Vol 107 (9) ◽  
pp. 1305-1315 ◽  
Author(s):  
Fatima Kasbi Chadli ◽  
Agnès Andre ◽  
Xavier Prieur ◽  
Gervaise Loirand ◽  
Anne Meynier ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Regulatory Element ◽  
Control Diet ◽  
Scavenger Receptor ◽  
Hdl Cholesterol ◽  
Control Group ◽  
High Fat ◽  
Metabolic Disturbances

Glucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction and CVD. The aim of the present study was to analyse the preventive effect of n-3 PUFA (EPA and DHA) on lipid and carbohydrate disturbances and endothelial dysfunction. Three groups of adult hamsters were studied for 20 weeks: (1) control diet (Control); (2) high-fat diet (HF); (3) high-fat diet enriched with n-3 PUFA (HFn-3) groups. The increase in body weight and fat mass in the HF compared to the Control group (P < 0·05) was not found in the HFn-3 group. Muscle TAG content was similar in the Control and HF groups, but significantly lower in the HFn-3 group (P = 0·008). Glucose tolerance was impaired in the HF compared to the Control group, but this impairment was prevented by n-3 PUFA in the HFn-3 group (P < 0·001). Plasma TAG and cholesterol were higher in the HF group compared to the Control group (P < 0·001), but lower in the HFn-3 group compared to the HF group (P < 0·001). HDL-cholesterol was lower in the HFn-3 group compared to the Control and HF groups (P < 0·0005). Hepatic secretion of TAG was lower in the HFn-3 group compared to the HF group (P < 0·005), but did not differ from the Control group. Hepatic gene expression of sterol regulatory element-binding protein-1c, diacylglycerol O-acyltransferase 2 and stearyl CoA desaturase 1 was lower in the HFn-3 group, whereas carnitine palmitoyl transferase 1 and scavenger receptor class B type 1 expression was higher (P < 0·05). In adipocytes and adipose macrophages, PPARγ and TNFα expression was higher in the HF and HFn-3 groups compared to the Control group. Endothelium relaxation was higher in the HFn-3 (P < 0·001) than in the HF and Control groups, and was correlated with glucose intolerance (P = 0·03) and cholesterol (P = 0·0003). In conclusion, n-3 PUFA prevent some metabolic disturbances induced by high-fat diet and improve endothelial function in hamsters.

scholarly journals Differential effects of hypercaloric choice diets on insulin sensitivity in rats

2017 ◽  
Vol 232 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Charlene Diepenbroek ◽  
Leslie Eggels ◽  
Mariëtte T Ackermans ◽  
Eric Fliers ◽  
Andries Kalsbeek ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Free Choice ◽  
Saturated Fat ◽  
High Fat ◽  
Short Term ◽  
Sugar Water ◽  
Hepatic Insulin Sensitivity ◽  
Peripheral Insulin Sensitivity ◽  
High Sugar

We showed previously that rats on a free-choice high-fat, high-sugar (fcHFHS) diet become rapidly obese and develop glucose intolerance within a week. Interestingly, neither rats on a free-choice high-fat diet (fcHF), although equally obese and hyperphagic, nor rats on a free-choice high-sugar (fcHS) diet consuming more sugar water, develop glucose intolerance. Here, we investigate whether changes in insulin sensitivity contribute to the observed glucose intolerance and whether this is related to consumption of saturated fat and/or sugar water. Rats received either a fcHFHS, fcHF, fcHS or chow diet for one week. We performed a hyperinsulinemic–euglycemic clamp with stable isotope dilution to measure endogenous glucose production (EGP; hepatic insulin sensitivity) and glucose disappearance (Rd; peripheral insulin sensitivity). Rats on all free-choice diets were hyperphagic, but only fcHFHS-fed rats showed significantly increased adiposity. EGP suppression by hyperinsulinemia in fcHF-fed and fcHFHS-fed rats was significantly decreased compared with chow-fed rats. One week fcHFHS diet also significantly decreased Rd. Neither EGP suppression nor Rd was affected in fcHS-fed rats. Our results imply that, short-term fat feeding impaired hepatic insulin sensitivity, whereas short-term consumption of both saturated fat and sugar water impaired hepatic and peripheral insulin sensitivity. The latter likely contributed to glucose intolerance observed previously. In contrast, overconsumption of only sugar water affected insulin sensitivity slightly, but not significantly, in spite of similar adiposity as fcHF-fed rats and higher sugar intake compared with fcHFHS-fed rats. These data imply that the palatable component consumed plays a role in the development of site-specific insulin sensitivity.

scholarly journals Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Lisa S. Robison ◽  
Olivia J. Gannon ◽  
Melissa A. Thomas ◽  
Abigail E. Salinero ◽  
Charly Abi-Ghanem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mouse Model ◽  
Glucose Intolerance ◽  
Systemic Inflammation ◽  
Fat Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Increased Risk ◽  
Ad Mouse Model

Abstract Background Hypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observed years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high-fat diet and metabolic disease (e.g., obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex. Methods WT and 3xTg-AD male and female mice were fed a control (10% fat) or high-fat (HF 60% fat) diet from ~ 3–7 months of age, then tested for metabolic and hypothalamic disturbances. Results On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group. Conclusions These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.

scholarly journals Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis

2015 ◽  
Vol 227 (3) ◽  
pp. 179-191 ◽  
Author(s):  
Irene Andrés-Blasco ◽  
Andrea Herrero-Cervera ◽  
Ángela Vinué ◽  
Sergio Martínez-Hervás ◽  
Laura Piqueras ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
Hepatic Lipase ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Obese People ◽  
Alcoholic Fatty Liver

Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to global health, and their incidence is increasing at an alarming rate. Non-alcoholic fatty liver disease, which affects up to 90% of obese people and nearly 70% of the overweight, is commonly associated with MetS characteristics such as obesity, insulin resistance, hypertension and dyslipidemia. In the present study, we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat, high-cholesterol diet produced dyslipidemia including hypercholesterolemia, hypertriglyceridemia and increased non-esterified fatty acid levels. These changes were accompanied by glucose intolerance, pancreatic and hepatic inflammation and steatosis. In addition, compared with WT mice, HL−/− mice exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of CD4+Th17+ cells. Consistent with increased inflammation, livers from HL−/− mice had augmented activation of the stress SAPK/JNK- and p38-pathways compared with the activation levels of the kinases in livers from WT mice. Analysis of HL−/− and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in HL−/− mice without any other changes in inflammation or hepatic steatosis. Altogether, these results indicate that dyslipidemia induced by HL-deficiency in combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and inflammation in mice which are, at least in part, mediated by the activation of the stress SAPK/JNK- and p38-pathways. Future studies are warranted to asses the viability of therapeutic strategies based on the modulation of these kinases to reduce hepatic steatosis associated to lipase dysfunction.

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