Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner

We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early overnutrition and high-fat diet (HFD). Here, we investigated how HFD in Swiss Webster males and females during preweaning, peripubertal, and post-pubertal periods alters glucose homeostasis and diabetes susceptibility. In males, HFD throughout life resulted in the highest diabetes incidence. Notably, switching to chow post-puberty was protective against diabetes relative to switching to chow at weaning, despite the longer period of HFD exposure. Similarly, HFD throughout life in males resulted in less liver steatosis relative to mice with shorter duration of postpubertal HFD. Thus, HFD timing relative to weaning and puberty, not simply exposure length, contributes to metabolic outcomes. Females were protected from hyperglycemia regardless of length or timing of HFD. However, postpubertal HFD resulted in a high degree of hepatic steatosis and adipose fibrosis, but glucose regulation and insulin sensitivity remained unchanged Interestingly, peri-insulitis was observed in the majority of females but was not correlated with impaired glucose regulation. Our findings reveal critical periods of HFD-induced glucose dysregulation with striking sex differences in Swiss Webster mice, highlighting the importance of careful consideration of HFD timing relative to critical developmental periods.

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Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

Journal of Endocrinology ◽

10.1530/joe-13-0526 ◽

2014 ◽

Vol 221 (3) ◽

pp. 381-390 ◽

Cited By ~ 21

Author(s):

Gustavo W Fernandes ◽

Cintia B Ueta ◽

Tatiane L Fonseca ◽

Cecilia H A Gouveia ◽

Carmen L Lancellotti ◽

...

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Liver Steatosis ◽

Mrna Levels ◽

High Fat ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

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Early overnutrition in male mice negates metabolic benefits of a diet high in monounsaturated and omega-3 fats

Scientific Reports ◽

10.1038/s41598-021-93409-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria M. Glavas ◽

Queenie Hui ◽

Ian Miao ◽

Fan Yang ◽

Suheda Erener ◽

...

Keyword(s):

Weight Gain ◽

High Fat Diet ◽

Diabetes Incidence ◽

Omega 3 ◽

High Fat ◽

Beneficial Effects ◽

Saturated Fats ◽

Glucose Dysregulation ◽

Fat Composition

AbstractOverconsumption of saturated fats promotes obesity and type 2 diabetes. Excess weight gain in early life may be particularly detrimental by promoting earlier diabetes onset and potentially by adversely affecting normal development. In the present study we investigated the effects of dietary fat composition on early overnutrition-induced body weight and glucose regulation in Swiss Webster mice, which show susceptibility to high-fat diet-induced diabetes. We compared glucose homeostasis between a high-fat lard-based (HFL) diet, high in saturated fats, and a high-fat olive oil/fish oil-based (HFO) diet, high in monounsaturated and omega-3 fats. We hypothesized that the healthier fat profile of the latter diet would improve early overnutrition-induced glucose dysregulation. However, early overnutrition HFO pups gained more weight and adiposity and had higher diabetes incidence compared to HFL. In contrast, control pups had less weight gain, adiposity, and lower diabetes incidence. Plasma metabolomics revealed reductions in various phosphatidylcholine species in early overnutrition HFO mice as well as with diabetes. These findings suggest that early overnutrition may negate any beneficial effects of a high-fat diet that favours monounsaturated and omega-3 fats over saturated fats. Thus, quantity, quality, and timing of fat intake throughout life should be considered with respect to metabolic health outcomes.

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Phenolic-enriched blueberry-leaf extract attenuates glucose homeostasis, pancreatic β-cell function, and insulin sensitivity in high-fat diet–induced diabetic mice

Nutrition Research ◽

10.1016/j.nutres.2019.09.005 ◽

2020 ◽

Vol 73 ◽

pp. 83-96 ◽

Cited By ~ 5

Author(s):

Hua Li ◽

Hye-Mi Park ◽

Hyeon-Seon Ji ◽

Jisu Han ◽

Sang-Kyum Kim ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Leaf Extract ◽

Cell Function ◽

Pancreatic Β Cell ◽

Diabetic Mice ◽

High Fat ◽

Β Cell ◽

Β Cell Function

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Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota

Microorganisms ◽

10.3390/microorganisms8060860 ◽

2020 ◽

Vol 8 (6) ◽

pp. 860 ◽

Cited By ~ 1

Author(s):

Yinzhao Zhong ◽

Bo Song ◽

Changbing Zheng ◽

Shiyu Zhang ◽

Zhaoming Yan ◽

...

Keyword(s):

Acetic Acid ◽

Lipid Metabolism ◽

Gut Microbiota ◽

High Fat Diet ◽

Control Diet ◽

Liver Steatosis ◽

High Fat ◽

Acetic Acid Production ◽

Mulberry Leaves ◽

Brown Adipose

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production.

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Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000374037 ◽

2015 ◽

Vol 35 (6) ◽

pp. 2349-2359 ◽

Cited By ~ 42

Author(s):

Youli Xi ◽

Miaozong Wu ◽

Hongxia Li ◽

Siqi Dong ◽

Erfei Luo ◽

...

Keyword(s):

Protein Kinase ◽

Fatty Liver ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Liver Steatosis ◽

Serum Levels ◽

Whole Body ◽

Therapeutic Effects ◽

High Fat ◽

Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

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Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure and postnatal high‑fat diet

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.6256 ◽

2018 ◽

Cited By ~ 2

Author(s):

Ching‑Chou Tsai ◽

Yu‑Ju Lin ◽

Hong‑Ren Yu ◽

Jiunn‑Ming Sheen ◽

You‑Lin Tain ◽

...

Keyword(s):

High Fat Diet ◽

Liver Steatosis ◽

High Fat

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Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

Food & Function ◽

10.1039/d1fo01394g ◽

2021 ◽

Author(s):

Haizhao Song ◽

Xinchun Shen ◽

Yang Zhou ◽

Xiaodong Zheng

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Liver Steatosis ◽

Obese Mice ◽

Black Rice ◽

High Fat ◽

Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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