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Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets.

ABSTRACT: White adipose tissue (WAT) plays an important role in obesity pathophysiology. Redox signaling underlies several aspects of WAT physiology; however, the thiol redox environment of WAT has not yet been fully characterized. Dietary and endocrine disrupting chemical (EDC) exposures during development can transiently impact the cellular redox environment, but it is unknown whether these exposures can reprogram the WAT thiol redox environment. To characterize the WAT thiol redox environment, we took a descriptive approach and measured thiol redox parameters using high-performance liquid chromatography in mouse mesenteric (mWAT), gonadal (gWAT) and subinguinal (sWAT) depots. Cysteine (CYSS:CYS) and glutathione (GSSG:GSH) redox potentials (Eh) were more oxidizing in gWAT and sWAT than mWAT. Increased body weight, relative WAT weight and age were associated with oxidizing GSSG:GSH Eh in mWAT in a sex-specific manner. Body weight and relative WAT weight were also positively associated with GSSG:GSH Eh in sWAT. We carried out a second mouse study with perinatal exposures to bisphenol A (BPA) and Mediterranean and Western high-fat diets (HFDs) to determine whether early-life chemical and dietary factors have long-lasting impacts on mWAT redox parameters. Mice exposed to Mediterranean HFD or BPA had more oxidizing GSSG:GSH mWAT Eh than controls, with more pronounced differences in females. These findings suggest an important role for the thiol redox environment in WAT physiology. Observed sex-specific and depot-specific differences in thiol redox parameters are consistent with known WAT physiology. Lastly, mWAT GSSG:GSH Eh may be reprogrammed by developmental exposure to HFDs and EDCs, which may have implications for obesity risk.

SUBMITTER: Neier K

PROVIDER: S-EPMC7003727 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets.

Neier Kari K Marchlewicz Elizabeth M EM Bedrosian Leah D LD Dolinoy Dana C DC Harris Craig C

The Journal of nutritional biochemistry 20190118

White adipose tissue (WAT) plays an important role in obesity pathophysiology. Redox signaling underlies several aspects of WAT physiology; however, the thiol redox environment of WAT has not yet been fully characterized. Dietary and endocrine disrupting chemical (EDC) exposures during development can transiently impact the cellular redox environment, but it is unknown whether these exposures can reprogram the WAT thiol redox environment. To characterize the WAT thiol redox environment, we took ...[more]

PMID: 30776609

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Project description:Background: The timing of puberty is highly sensitive to environmental factors, including endocrine disruptors. Among them, bisphenol A (BPA) has been previously analyzed as potential modifier of puberty. Yet, disparate results have been reported, with BPA advancing, delaying, or being neutral in its effects on puberty onset. Likewise, mechanistic analyses addressing the central and peripheral actions/targets of BPA at puberty remain incomplete and conflictive.Objective: We aimed to provide a comprehensive characterization of the impact of early BPA exposures, especially at low, real-life doses, on the postnatal development of hypothalamic Kiss1/NKB neurons, and its functional consequences on female pubertal maturation.Methods: Pregnant CD1 female mice were orally administered BPA at 5, 10, or 40μg/kg body weight (BW)/d from gestational day 11 to postnatal day 8 (PND8). Vaginal opening, as an external marker of puberty onset, was monitored daily from PND19 to PND30 in the female offspring. Blood and brain samples were collected at PND12, 15, 18, 21, and 30 for measuring circulating levels of gonadotropins and analyzing the hypothalamic expression of Kiss1/kisspeptin and NKB.Results: Perinatal exposure to BPA, in a range of doses largely below the no observed adverse effect level (NOAEL; 5mg/kg BW/d, according to the FDA), was associated with pubertal differences in the female progeny compared with those exposed to vehicle alone, with an earlier age of vaginal opening but consistently lower levels of circulating luteinizing hormone. Mice treated with BPA exhibited a persistent, but divergent, impairment of Kiss1 neuronal maturation, with more kisspeptin cells in the rostral (RP3V) hypothalamus but consistently fewer kisspeptin neurons in the arcuate nucleus (ARC). Detailed quantitative analysis of the ARC population, essential for pubertal development, revealed that mice treated with BPA had persistently lower Kiss1 expression during (pre)pubertal maturation, which was associated with lower Tac2 (encoding NKB) levels, even at low doses (5μg/kg BW/d), in the range of the tolerable daily intake (TDI), recently updated by the European Food Safety Authority.Conclusions: Our data attest to the consistent, but divergent, effects of gestational exposures to low concentrations of BPA, via the oral route, on phenotypic and neuroendocrine markers of puberty in female mice, with an unambiguous impact on the developmental maturation not only of Kiss1, but also of the NKB system, both essential regulators of puberty onset. https://doi.org/10.1289/EHP5570.

Dataset Information

Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets.

Publications

Characterization of the mouse white adipose tissue redox environment and associations with perinatal environmental exposures to bisphenol A and high-fat diets.

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