Oxidative Stress in the Visceral Fat Is Elevated in Postmenopausal Women with Gynecologic Cancer

J Womens Health (Larchmt). 2018 Jan;27(1):99-106. doi: 10.1089/jwh.2016.6301. Epub 2017 Aug 17.

Abstract

Objectives: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes.

Materials and methods: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive oxygen species (ROS) production that was induced by hydrogen peroxide (H2O2) in 3T3-L1 adipocytes.

Results: The visceral adipocytes were 1162.4 μm2 and 1881.9 μm2 in premenopausal and postmenopausal women, respectively; hence they were significantly larger in the latter (p < 0.05). The lipid peroxidation levels were 46.7 nmoL/mg protein in premenopausal women and 99.6 nmoL/mg protein in postmenopausal women; hence the lipid peroxidation levels were significantly higher in the latter (p < 0.05). Estradiol (E2) significantly reduced the intracellular ROS levels that were induced by H2O2 in 3T3-L1 adipocytes (p < 0.01). We determined that E2 significantly increased the expression of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant genes, heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and the glutamate-cysteine ligase (GCL) modifier subunit genes, in 3T3-L1 adipocytes (p < 0.01).

Conclusion: Oxidative stress in the visceral fat is higher in postmenopausal women. The expression of the antioxidant genes HO-1, NQO1, and GCL was upregulated by estrogen in 3T3-L1 adipocytes. Hence, estrogen may act as an antioxidant in the adipose tissues of premenopausal women.

Keywords: adipocyte; estrogen; menopause; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells / drug effects*
  • Animals
  • Estrogens / pharmacology*
  • Female
  • Genital Neoplasms, Female / complications*
  • Glutamate-Cysteine Ligase
  • Heme Oxygenase-1 / drug effects*
  • Humans
  • Hydrogen Peroxide
  • Intra-Abdominal Fat / metabolism*
  • Lipid Peroxidation
  • Mice
  • NAD(P)H Dehydrogenase (Quinone)
  • NF-E2-Related Factor 2 / drug effects*
  • Oxidative Stress*
  • Postmenopause*
  • Premenopause*

Substances

  • Estrogens
  • NF-E2-Related Factor 2
  • Hydrogen Peroxide
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Glutamate-Cysteine Ligase