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

J Nutr Biochem. 2019 Apr;66:86-97. doi: 10.1016/j.jnutbio.2019.01.005. Epub 2019 Jan 18.

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.

Keywords: Developmental programming; Endocrine disruptors; Glutathione; Obesity; Redox potentials; White adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Adiposity
  • Animals
  • Benzhydryl Compounds / toxicity*
  • Body Weight
  • Chromatography, High Pressure Liquid
  • Cysteine / metabolism
  • Diet, High-Fat / adverse effects*
  • Diet, Mediterranean
  • Diet, Western / adverse effects
  • Environmental Exposure / adverse effects*
  • Female
  • Glutathione / metabolism
  • Longitudinal Studies
  • Male
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Oxidation-Reduction
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects

Substances

  • Benzhydryl Compounds
  • Phenols
  • Glutathione
  • Cysteine
  • bisphenol A