Perinatal Exposure to Bisphenol-A and the Development of Metabolic Syndrome in CD-1 Mice

Bisphenol-A (BPA) is an endocrine-disrupting chemical used in the production of plastic food and beverage containers, leading to ubiquitous low-dose human exposure. It has been suggested that exposure to even low doses of BPA during development may be associated with increased susceptibility to obesity and diabetes later in life. Despite growing public concern, the existing empirical data are equivocal, prompting The Endocrine Society, the National Institute of Environmental Health Sciences, and others to call for further research. In this study, we tested the hypothesis that perinatal exposure to an ecologically relevant dose of BPA (1 part per billion via the diet) results in increased susceptibility to high-fat diet-induced obesity and glucose intolerance in adult CD-1 mice. The data did not support this hypothesis. In agreement with previous reports, we find that weanling mice exposed to BPA during gestation and lactation are heavier compared with control mice. We also find that BPA mice are longer than controls at 4 wk of age, but these differences are no longer apparent when the mice reach adulthood, even when tested on a high-fat diet. We conclude that this larger size-for-age represents a faster rate of growth early in development rather than an obese, diabetic phenotype in adulthood.

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Perinatal Exposure to Bisphenol A at Reference Dose Predisposes Offspring to Metabolic Syndrome in Adult Rats on a High-Fat Diet

Endocrinology ◽

10.1210/en.2011-0045 ◽

2011 ◽

Vol 152 (8) ◽

pp. 3049-3061 ◽

Cited By ~ 192

Author(s):

Jie Wei ◽

Yi Lin ◽

Yuanyuan Li ◽

Chenjiang Ying ◽

Jun Chen ◽

...

Keyword(s):

Metabolic Syndrome ◽

Bisphenol A ◽

High Fat Diet ◽

Perinatal Exposure ◽

High Fat ◽

Adult Rats ◽

Reference Dose

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Oral Bisphenol A Worsens Liver Immune-Metabolic and Mitochondrial Dysfunction Induced by High-Fat Diet in Adult Mice: Cross-Talk between Oxidative Stress and Inflammasome Pathway

Antioxidants ◽

10.3390/antiox9121201 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1201

Author(s):

Claudio Pirozzi ◽

Adriano Lama ◽

Chiara Annunziata ◽

Gina Cavaliere ◽

Clara Ruiz-Fernandez ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Bisphenol A ◽

Mitochondrial Dysfunction ◽

Cross Talk ◽

High Fat Diet ◽

Additional Risk Factor ◽

High Fat ◽

Endocrine Disrupting Chemical ◽

Glucose And Lipid Metabolism

Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression. This study evidences that BPA exposure represents an additional risk factor for the progression of fatty liver diseases strictly related to the cross-talk between oxidative stress and immune-metabolic impairment due to obesity.

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Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

Journal of Endocrinology ◽

10.1530/joe-14-0356 ◽

2014 ◽

Vol 222 (3) ◽

pp. 313-325 ◽

Cited By ~ 55

Author(s):

Jie Wei ◽

Xia Sun ◽

Yajie Chen ◽

Yuanyuan Li ◽

Liqiong Song ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Liver Function ◽

Bisphenol A ◽

Insulin Signaling ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Perinatal Exposure ◽

High Fat ◽

Rat Offspring

Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 μg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population.

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Green tea catechins attenuate high-fat diet effects related to obesity and diabetes without effect hypothalamic expression of TLR4 pathway or serotoninergic 1B and 2C receptors

Endocrine Abstracts ◽

10.1530/endoabs.32.p746 ◽

2013 ◽

Author(s):

Marcos Hiromu Okuda ◽

de Santana Aline Alves ◽

Mayara Franzoi Moreno ◽

Ana Claudia Hachul ◽

Nelson Inacio Neto ◽

...

Keyword(s):

Green Tea ◽

High Fat Diet ◽

High Fat ◽

Tea Catechins ◽

Green Tea Catechins ◽

Obesity And Diabetes

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High-Fat Diet and Age-Dependent Effects of IgA-Bearing Cell Populations in the Small Intestinal Lamina Propria in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22031165 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1165

Author(s):

Yuta Sakamoto ◽

Masatoshi Niwa ◽

Ken Muramatsu ◽

Satoshi Shimo

Keyword(s):

Immune Function ◽

Lamina Propria ◽

High Fat Diet ◽

Immunoglobulin A ◽

Immune Functions ◽

High Fat ◽

Intestinal Villi ◽

Diet Induced Obesity ◽

Obesity And Diabetes

Several studies highlighted that obesity and diabetes reduce immune function. However, changes in the distribution of immunoglobins (Igs), including immunoglobulin-A (IgA), that have an important function in mucosal immunity in the intestinal tract, are unclear. This study aimed to investigate the impaired immune functions in the context of a diet-induced obese murine model via the assessment of the Igs in the intestinal villi. We used mice fed a high-fat diet (HFD) from four to 12 or 20 weeks of age. The distributions of IgA, IgM, and IgG1 were observed by immunohistochemistry. Interestingly, we observed that IgA was immunolocalized in many cells of the lamina propria and that immunopositive cells increased in mice aged 12 to 20 weeks. Notably, mice fed HFD showed a reduced number of IgA-immunopositive cells in the intestinal villi compared to those fed standard chow. Of note, the levels of IgM and IgG1 were also reduced in HFD fed mice. These results provide insights into the impaired mucosal immune function arising from diet-induced obesity and type 2 diabetes.

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Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet

Endocrinology ◽

10.1210/en.2009-1295 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1598-1610 ◽

Cited By ~ 104

Author(s):

Maria M. Glavas ◽

Melissa A. Kirigiti ◽

Xiao Q. Xiao ◽

Pablo J. Enriori ◽

Sarah K. Fisher ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

High Fat Diet ◽

Arcuate Nucleus ◽

Leptin Resistance ◽

Signal Transducer ◽

High Fat ◽

Insulin Tolerance ◽

Obesity And Diabetes ◽

Transcription 3

Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in response to a high-fat diet (HFD). Litters from Swiss Webster dams were culled to three [chronic postnatal overnutrition (CPO)] or 10 (control) pups and then weaned onto standard chow at postnatal day (P) 23. At 6 wk of age, a subset of mice was placed on HFD, and glucose and insulin tolerance were examined at 16–17 wk of age. Leptin sensitivity was determined by hypothalamic phosphorylated signal transducer and activator of transcription-3 immunoreactivity at P16 and adulthood after ip leptin. CPO mice exhibited accelerated body weight gain and hyperleptinemia during the preweaning period but only a slightly heavier body weight and normal glucose tolerance in adulthood on standard chow diet. Importantly, CPO mice exhibited significant leptin resistance in the arcuate nucleus, demonstrated by reduced activation of phospho-signal transducer and activator of transcription-3, as early as P16 and throughout life, despite normalized leptin levels. In response to HFD, CPO but not control mice displayed insulin resistance in response to an insulin tolerance test. In conclusion, CPO mice exhibited early and persistent leptin resistance in the arcuate nucleus and, in response to HFD, rapid development of obesity and insulin resistance. These studies suggest that early overnutrition can permanently alter energy homeostasis and significantly increase susceptibility to obesity and insulin resistance.

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Yarrow Supercritical Extract Ameliorates the Metabolic Stress in a Model of Obesity Induced by High-Fat Diet

Nutrients ◽

10.3390/nu12010072 ◽

2019 ◽

Vol 12 (1) ◽

pp. 72 ◽

Cited By ~ 2

Author(s):

Lamia Mouhid ◽

Marta Gómez de Cedrón ◽

Adriana Quijada-Freire ◽

Pablo J. Fernández-Marcos ◽

Guillermo Reglero ◽

...

Keyword(s):

High Fat Diet ◽

Metabolic Stress ◽

Standard Diet ◽

Model Assessment ◽

High Fat ◽

Glucose Levels ◽

Nutraceutical Compounds ◽

Fasting Glycemia ◽

Obesity And Diabetes ◽

Potential Therapeutic Role

Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose.

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Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00500.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. E31-E41 ◽

Cited By ~ 90

Author(s):

Robert C. Noland ◽

John P. Thyfault ◽

Sarah T. Henes ◽

Brian R. Whitfield ◽

Tracey L. Woodlief ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Gain ◽

High Fat Diet ◽

Oxidative Capacity ◽

Male Rats ◽

High Fat ◽

Endurance Running ◽

Muscle Oxidative Capacity ◽

Obesity And Diabetes

Elevated oxidative capacity, such as occurs via endurance exercise training, is believed to protect against the development of obesity and diabetes. Rats bred both for low (LCR)- and high (HCR)-capacity endurance running provide a genetic model with inherent differences in aerobic capacity that allows for the testing of this supposition without the confounding effects of a training stimulus. The purpose of this investigation was to determine the effects of a high-fat diet (HFD) on weight gain patterns, insulin sensitivity, and fatty acid oxidative capacity in LCR and HCR male rats in the untrained state. Results indicate chow-fed LCR rats were heavier, hypertriglyceridemic, less insulin sensitive, and had lower skeletal muscle oxidative capacity compared with HCR rats. Upon exposure to an HFD, LCR rats gained more weight and fat mass, and their insulin resistant condition was exacerbated, despite consuming similar amounts of metabolizable energy as chow-fed controls. These metabolic variables remained unaltered in HCR rats. The HFD increased skeletal muscle oxidative capacity similarly in both strains, whereas hepatic oxidative capacity was diminished only in LCR rats. These results suggest that LCR rats are predisposed to obesity and that expansion of skeletal muscle oxidative capacity does not prevent excess weight gain or the exacerbation of insulin resistance on an HFD. Elevated basal skeletal muscle oxidative capacity and the ability to preserve liver oxidative capacity may protect HCR rats from HFD-induced obesity and insulin resistance.

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