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Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A.

ABSTRACT: The increased pericardial fat which often accompanies overall obesity is thought to alter cardiac structure/function and increase the risk for atrial fibrillation. We hypothesized that chronic exposure to bisphenol A (BPA) would induce pericardial fat, cardiac hypertrophy or arrhythmia. C57bl/6n dams were exposed to BPA (25 ng/ml drinking water) beginning on gestation day 11 and progeny continued on 2.5 ng BPA/ml drinking water. The progeny of control dams (VEH) and dams treated with diethylstilbestrol (DES, 1 ?g/kg/day, gestation days 11?14) had tap water. After weaning progeny were fed either a control (CD) or high fat diet (HFD) for 3 months. Pericardial fat was present in CD-BPA and CD-DES and not CD-VEH mice, and was increased in all HFD mice. Catecholamine challenge revealed no differences in males, but BPA-exposed females had longer P-wave and QRS complex duration. Only CD-BPA and CD-DES females developed cardiac hypertrophy which was independent of increased blood pressure. Calcium homeostasis protein expression changes in HFD-BPA and HFD-DES mice predict reduced SERCA2 activity in males and increased SERCA2 activity in females. Thus, chronic BPA exposure induced pericardial fat in the absence of HFD, and female-specific changes in cardiac hypertrophy development and cardiac electrical conduction after a catecholamine challenge.

SUBMITTER: Patel BB

PROVIDER: S-EPMC5598525 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A.

Patel Bhavini B BB Raad Mohamad M Sebag Igal A IA Chalifour Lorraine E LE

Toxicology reports 20151001

The increased pericardial fat which often accompanies overall obesity is thought to alter cardiac structure/function and increase the risk for atrial fibrillation. We hypothesized that chronic exposure to bisphenol A (BPA) would induce pericardial fat, cardiac hypertrophy or arrhythmia. C57bl/6n dams were exposed to BPA (25 ng/ml drinking water) beginning on gestation day 11 and progeny continued on 2.5 ng BPA/ml drinking water. The progeny of control dams (VEH) and dams treated with diethylstil ...[more]

PMID: 28962473

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Project description:Background/objectiveFemale mice are often excluded from diet-induced obesity studies as they are more resistant to the obesifying effects of a high-fat diet (HFD). However, the underlying mechanisms behind this sex disparity may actually have important implications for the development and management of obesity in humans. Therefore, we systematically investigated the immediate sex-specific effects of transitioning to a HFD in C57BL/6J mice as well as monitored whether these effects are altered after sustained HFD feeding and whether sex affects the response to a return to chow, representative of dieting.MethodsDual X-ray absorptiometry (DXA) analysis of body composition, indirect calorimetry measurements, and qPCR analysis of hypothalamic and brainstem regions were performed on male and female C57BL/6J mice.ResultsHFD had immediate and dramatic effects in males, increasing fat mass by 58% in the first 3 days. The resistance to the obesifying effect of HFD in females was linked both to an ability to maintain activity levels as well as to an immediate and significantly enhanced reduction in respiratory quotient (RQ), suggesting a greater ability to utilise fat in the diet as a source of fuel. Mechanistically, this sex disparity may be at least partially due to inherent sex differences in the catabolic (POMC/CART) versus anabolic (NPY/AgRP) neurological signalling pathways. Interestingly, the reintroduction of chow following HFD had immediate and consistent responses between the sexes with body composition and most metabolic parameters normalised within 3 days. However, both sexes displayed elevated hypothalamic Npy levels reminiscent of starvation. The difference in RQ seen between the sexes on HFD was immediately abolished suggesting similar abilities to burn fat reserves for fuel.ConclusionsC57BL/6J mice have markedly different sex-specific behavioural and metabolic responses to the introduction as well as the sustained intake of a HFD, but consistent responses to a dieting situation.

Project description:Overweight and obesity are major public health challenges worldwide. Obesity is associated with a higher risk for the development of several cancer types, but specific mechanisms underlying the link of obesity and cancer are still unclear. Natural killer (NK) cells are circulating lymphoid cells promoting the elimination of virus-infected and tumor cells. Previous investigations demonstrated conflicting results concerning the influence of obesity on functional NK cell parameters in small animal models. The aim of the present study was to clarify potential obesity-associated alterations of murine NK cells in vivo, implementing different feeding regimes. Therefore, C57BL/6 mice were fed a normal-fat diet (NFD) or high-fat diet (HFD) under restrictive and ad libitum feeding regimes. Results showed diet and feeding-regime dependent differences in body weight, visceral fat mass and plasma cytokine concentrations. Flow cytometry analyses demonstrated significant changes in total cell counts as well as frequencies of immune cell populations in peripheral blood comparing mice fed NFD or HFD in an ad libitum or restrictive manner. Mice fed the HFD showed significantly decreased frequencies of total NK cells and the mature CD11b+CD27+ NK cell subset compared to mice fed the NFD. Feeding HFD resulted in significant changes in the expression of the maturation markers KLRG1 and CD127 in NK cells. Furthermore, real-time PCR analyses of NK-cell related functional parameters in adipose tissue revealed significant diet and feeding-regime dependent differences. Most notable, real-time cytotoxicity assays demonstrated an impaired cytolytic activity of splenic NK cells toward murine colon cancer cells in HFD-fed mice compared to NFD-fed mice. In conclusion, our data demonstrate that feeding a high-fat diet influences the frequency, phenotype and function of NK cells in C57BL/6 mice. Interestingly, restricted feeding of HFD compared to ad libitum feeding resulted in a partial prevention of the obesity-associated alterations on immune cells and especially on NK cells, nicely fitting with the current concept of an advantage for interval fasting for improved health.

Dataset Information

Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A.

Publications

Sex-specific cardiovascular responses to control or high fat diet feeding in C57bl/6 mice chronically exposed to bisphenol A.

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