Age, Sex, and Depot-Specific Differences in Adipose-Tissue Estrogen Receptors in Individuals with Obesity

Abstract

Objective: The aim of this study was to examine the effects of sex and menopausal status on depot-specific estrogen signaling in white adipose tissue (AT) in age-matched men and women with morbid obesity.

Methods: A total of 28 premenopausal women, 16 postmenopausal women, and 27 age-matched men undergoing bariatric surgery were compared for omental (OM) AT (OMAT) and abdominal subcutaneous (SQ) AT (SQAT) genes and proteins.

Results: With the exception of fasting nonesterified fatty acids being higher in women (P < 0.01), no differences were found in other indicators of glucose and lipid metabolism. In OMAT, estrogen receptor (ER) beta (ERβ) levels were higher in older women than in younger women and older men (sex-age interaction, P < 0.01), and aromatase expression was higher in older men than in older women (P < 0.05). In SQAT, women had lower expression of ERβ than men (P < 0.05). Protein content of ER alpha and ERβ was highly correlated with the mitochondrial protein uncoupling protein 1 across sexes and ages (P < 0.001). Age increased SQ inflammatory gene expression in both sexes.

Conclusions: In morbid obesity, sex and age affect AT ERs, lipid metabolism, mitochondrial uncoupling protein 1, and inflammatory expression in an AT depot-dependent manner. The SQAT immunometabolic profile is heavily influenced by age and menopause status, more so than OMAT.

Trial registration: ClinicalTrials.gov NCT03419273.

Conflict of interest statement

Disclosure: The authors declared no conflict of interest.

© 2020 The Obesity Society.

Figures

Figure 1.

ER gene expression and protein content. OMAT gene expression (A), SQ adipose tissue gene expression (B), OM adipose tissue protein content (C), and SQ adipose tissue protein content (D); OM ratio of ER subtype expression (E); SQ ratio of ER subtype expression (F). ERα - estrogen receptor alpha; ERβ - estrogen receptor beta. Values are means ± SEM.; SP<0.05 main effect of sex; AP<0.05 main effect of age; S*AP<0.05 sex by age interaction; &p<0.05 Tukey post hoc different than Female-Young; and #p<0.05 Tukey post hoc different than Male-Old.

Figure 2.

Omental immunometabolic characteristics. OM adipose tissue protein content (A), and gene expression (mRNA) (B). Akt - protein kinase B; GLUT4, glucose transporter 4; NFkB - nuclear factor kappa-light-chain-enhancer of activated B cells; ACC - acetyl CoA carboxylase; HSL - hormone sensitive lipase; UCP1 - uncoupling protein 1; TNFα - tumor necrosis factor alpha; IL6 - interleukin 6; IL1β - interleukin 1 beta; LPL - lipoprotein lipase; ATGL - adipose tissue triglyceride lipase. Values are means ± SEM; SP<0.05 main effect of sex; AP<0.055 main effect of age; S*AP<0.05 sex by age interaction; #p<0.05 Tukey post hoc different than Male-Old.

Figure 3.

Subcutaneous immunometabolic characteristics. SQAT protein content (A), and gene expression (mRNA) (B). Akt - protein kinase B; GLUT4 - glucose transporter 4; NFkB - nuclear factor kappa-light-chain-enhancer of activated B cells; ACC - acetyl CoA carboxylase; HSL - hormone sensitive lipase; UCP1 - uncoupling protein 1; TNFα - tumor necrosis factor alpha; IL6 - interleukin 6; IL1β - interleukin 1 beta; LPL - lipoprotein lipase; ATGL - adipose tissue triglyceride lipase. Values are means ± SEM; SP<0.05 main effect of sex; AP<0.055 main effect of age; S*AP<0.05 sex by age interaction; #p<0.05 Tukey post hoc different than Male-Old.

Figure 4.

Pearson Correlations for omental and subcutaneous adipose tissue Protein content of UCP1 and protein content of ERα (A), protein content of UCP1 and ERβ (B), Leptin expression and the ratio of ER subtypes in subcutaneous (SQ) and omental (OM) adipose tissue (C). UCP1 - uncoupling protein 1; ERα - estrogen receptor alpha; ERβ - estrogen receptor beta; SQ-OM ratio, gene expression ratio of SQ(ERα:ERβ):OM(ERα:ERβ).