Exposure to Bisphenol-A during Pregnancy Partially Mimics the Effects of a High-Fat Diet Altering Glucose Homeostasis and Gene Expression in Adult Male Mice

Epidemiological findings on the association between bisphenol A (BPA, 2,2-bis-(4-hydroxyphenyl)propane) exposure and type 2 diabetes mellitus (T2DM) are paradoxical. In animal studies, BPA has been shown to disrupt pancreatic function and blood glucose homeostasis even at a reference ‘safe’ level during perinatal period. In this study, we explored the effects of long-term paternal exposure to a ‘safe’ level of BPA on parents themselves and their offspring. Adult male genitor rats fed with either standard chow diet (STD) or high-fat diet (HFD) were treated respectively with either vehicle or BPA (50 μg/kg per day) for 35 weeks. The male rats treated with vehicle or BPA for 21 weeks were then used as sires, and the adult female rats were fed with STD during the gestation and lactation. Offspring rats were weaned on postnatal day 21 and fed with STD in later life. Metabolic parameters were recorded on the adult male rats and their adult offspring. BPA exposure disrupted glucose homeostasis and pancreatic function, and HFD aggravated these adverse effects. However, BPA exposure did not alter body weight, body fat percentage, or serum lipid. In addition, the paternal BPA exposure did not cause adverse reproductive consequence or metabolic disorder in the adult offspring. Our findings indicate that chronic exposure to a predicted ‘safe’ dose of BPA contributes to glucose metabolic disorders, and that HFD aggravates these adverse effects in paternal rats.

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Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2015.02.021 ◽

2015 ◽

Vol 284 (2) ◽

pp. 101-112 ◽

Cited By ~ 73

Author(s):

Rita S. Strakovsky ◽

Huan Wang ◽

Nicki J. Engeseth ◽

Jodi A. Flaws ◽

William G. Helferich ◽

...

Keyword(s):

Gene Expression ◽

Bisphenol A ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Hepatic Gene Expression ◽

High Fat ◽

Specific Modification

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EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation ofDnmt1andMLH1in C57BL/6J Male Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3079148 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 37

Author(s):

Marlene Remely ◽

Franziska Ferk ◽

Sonja Sterneder ◽

Tahereh Setayesh ◽

Sylvia Roth ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Damage ◽

Gut Microbiota ◽

High Fat Diet ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Male Mice ◽

High Fat ◽

Methyltransferase 1

Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression ofDNA methyltransferase 1,interleukin 6, andMutL homologue 1were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns ofDNA methyltransferase 1andMutL homologue 1. HFD feeding caused a significant lower bacterial abundance. TheFirmicutes/Bacteroidetesratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements.

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Effect of high-fat diet on glucose homeostasis and gene expression in glucokinase knockout mice

Diabetes Obesity and Metabolism ◽

10.1111/j.1463-1326.2007.00819.x ◽

2008 ◽

Vol 10 (10) ◽

pp. 885-897 ◽

Cited By ~ 18

Author(s):

T. Gorman ◽

D. C. D. Hope ◽

R. Brownlie ◽

A. Yu ◽

D. Gill ◽

...

Keyword(s):

Gene Expression ◽

Glucose Homeostasis ◽

Knockout Mice ◽

High Fat Diet ◽

High Fat

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Gene Expression Profiling in Liver of Mice Fed a High-Fat Diet Supplemented With Watermelon Flesh, Arginine, or Citrulline Shows Similar Pattern Changes

Current Developments in Nutrition ◽

10.1093/cdn/nzab037_013 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 303-303

Author(s):

Mikayla Chen ◽

Neil Shay

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Expression Patterns ◽

Cytochrome P450 Monooxygenases ◽

Mrna Levels ◽

Male Mice ◽

High Fat ◽

Total Rna ◽

P450 Monooxygenases ◽

Close Relationship

Abstract Objectives Watermelon is a nutrient-dense fruit known to contain high levels or arginine and citrulline; these two compounds may influence the nitric oxide pathway, vasodilation, and thus be hypotensive. We tested the hypothesis that when C57BL/6J male mice fed a high-fat diet (HF) had additions to the HF diet of either watermelon flesh (WF), arginine (ARG) or citrulline (CIT), changes in gene expression patterns would occur vs. those seen in HF. Further, we hypothesize that patterns of expression seen in WF, ARG, and CIT groups would be somewhat similar based on increased dietary levels of ARG and CIT in all three groups. Methods Following prior work (Becraft et al.; 2018, Egea et al. 2020), groups of mice were provided either a low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF plus Watermelon Flesh (WF), HF plus 1% (w/w) arginine (ARG) or 1% (w/w citrulline (CIT) for 10 weeks. Watermelon flesh was provided at 10% of total energy. After ten weeks, animals were euthanized, and liver total RNA was isolated using Trizol. Total RNA was then used for gene expression analysis (N = 4 per group) using Clariom S microarrays and TAC analysis software (ThermoFisher). Results Mice fed WF, ARG, and CIT had several shared canonical pathways of gene expression, including eicosanoid metabolism via cytochrome P450 monooxygenases and exercise-induced circadian rhythm (All P < 0.05). Intake of WF and ARG significantly up-regulated both Cyp2c9 and Cyp2c38 mRNA levels (P < 0.05). The Bst2 gene was significantly down-regulated in all three groups compared to HF mice (P < 0.05). The Cyp2b9 gene was upregulated ∼10.7 fold in WF, and > 1000-fold in ARG mice (P < 0.05). Conclusions We demonstrated that when added to a HF diet, WF, ARG, and CIT all produced a change in hepatic gene expression in male mice. Possibly due to the close relationship of ARG and CIT metabolism, and high content of ARG and CIT in WF, expression patterns observed in all three groups demonstrated a high degree of similarity. Several genes, including Cyp2c9, Cyp2c38, and Elvol5 were up-regulated; these genes may be involved in modifying steroids and arachidonic acid and other long-chain fatty acids. Funding Sources National Watermelon Promotion Board.

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Effect of inulin supplementation in male mice fed with high fat diet on biochemical profile and α-amylase gene expression

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v15i6.12 ◽

2016 ◽

Vol 15 (6) ◽

pp. 1197 ◽

Cited By ~ 2

Author(s):

Zahra Pouyamanesh ◽

Mahsa M Amoli ◽

Parichehreh Yaghmaei ◽

Azadeh Ebrahim-Habibi

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Biochemical Profile ◽

Male Mice ◽

High Fat ◽

Amylase Gene

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

Endocrinology ◽

10.1210/en.2015-1713 ◽

2015 ◽

Vol 157 (2) ◽

pp. 648-665 ◽

Cited By ~ 40

Author(s):

Vanessa Dubois ◽

Michaël R. Laurent ◽

Ferran Jardi ◽

Leen Antonio ◽

Katleen Lemaire ◽

...

Keyword(s):

Body Composition ◽

Androgen Receptor ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Hormone Sensitive Lipase ◽

Androgen Deficiency ◽

Male Mice ◽

High Fat ◽

Metabolic Alterations

Abstract 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.

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