Research Paper Volume 12, Issue 2 pp 1725—1746

Female adipose tissue has improved adaptability and metabolic health compared to males in aged obesity

Mita Varghese 1, , Cameron Griffin 1, , Kaitlin McKernan 1, , Leila Eter 1, , Simin Abrishami 1, , Kanakadurga Singer 1, ,

  • 1 Department of Pediatrics, Division of Endocrinology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

received: August 14, 2019 ; accepted: January 2, 2020 ; published: January 26, 2020 ;

https://doi.org/10.18632/aging.102709
How to Cite

Copyright © 2020 Mita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging, like obesity, is associated with metabolic and inflammatory alterations within adipose tissue in older individuals. Younger females are protected from adipose inflammation, but older post-menopausal females exhibit exaggerated visceral adiposity correlated with increased disease risk. Obesity accelerates the onset and progression of age-associated diseases, but it is unclear if aging and obesity drive adipose tissue dysfunction in a sexually dimorphic fashion. We investigated adipose tissue metabolism and inflammation in a diet-induced obesity model in young and old mice. We identified age related sex differences in adipose tissue macrophages (ATMs), fibrosis and lipid metabolism in male and female visceral fat depot (GWAT). Although aging normalized body weights between the sexes, females remained protected from proinflammatory ATMs and stimulated lipolysis failed to adversely affect the inflammatory state even with obesity. Older obese males had augmented CD11c+ ATMs and higher insulin levels, while females showed increased visceral adiposity and exaggerated Pparγ, and Pgc1α expression. Obesity in aging demonstrated similar expression of GWAT p53, p16, p21, Timp1 and Tgfβ1 in both sexes. Our studies suggest that even with aging, female GWAT shows an attenuated inflammatory response compared to males due to an efficient oxidative metabolism combined with an active tissue remodeling state.

Abbreviations

ND: normal diet; HFD: high fat diet; GWAT: gonadal adipose tissue; IWAT: inguinal adipose tissue; ADRB3: β3-adrenergic receptor; CL: CL-316,243; FFA: free fatty acid; TG: triglyceride; SVF: stromal vascular fraction; ATM: adipose tissue macrophage; DC: dendritic cell; ECM: extracellular matrix; MMPs: matrix metalloproteinases; TIMPs: tissue inhibitors of metalloproteinases; PCOS: polycystic ovary syndrome.