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

Aging-US Volume 12, Issue 2 reported that 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.

Dr. Kanakadurga Singer from the Department of Pediatrics, Division of Endocrinology at University of Michigan Medical School in Ann Arbor, Michigan USA said, "Aging is associated with an increased risk for cardiovascular diseases, especially in older men and women."

"Unlike immunologically “hot” tumors such as lung cancer, melanoma, and bladder cancer, most breast carcinomas are not inherently immunogenic."

- Dr. Kanakadurga Singer, Department of Pediatrics, Division of Endocrinology at University of Michigan Medical School

One potential factor may be the age-related increase in adipose tissue in women during menopause, leading to increased adipose tissue inflammation and an enhanced systemic pro-inflammatory environment prior to the stroke.

Figure 2. Aging and obesity promote pro-inflammatory ATMs in young and old male mice GWAT. (A) Representative flow cytometry gating strategy for CD64⁺CD11c⁺ ATMs in GWAT SVF derived from ND and HFD fed young and old mice. (B) top row- Immunofluorescence images of old male obese GWAT and old female obese GWAT depicting MAC-2 labeling of CLS (magenta) and CAV-1 labeling of adipocytes (green). Scale bar = 500 μm. (B) bottom row- H&E staining of GWAT sections depicting CLS in old obese male and females. Scale bar = 500 μm. Quantitation as a % of SVF of (C) GWAT ATMs (D) GWAT CD11c⁺ ATMs (E) GWAT CD11c^- ATMs. N=7-12/group. Two-way ANOVA with Bonferroni-Dunn’s post-test was performed for (C, E). Statistics from diet and sex interaction are in box. Statistical significance is indicated by *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. Student’s t-test was performed for male and female comparisons between the same diet groups indicated by ^#p<0.05, ^##p<0.01 ^###p<0.001 and ^####p<0.0001; error bars are SEM.

Obesity-induced inflammation is specifically characterized by the infiltration and retention of immune cells within the adipose tissue known as adipose tissue macrophages.

This type of adipose tissue inflammation, specifically within the visceral-gonadal white adipose tissue, has been linked to metabolic syndrome.

This study includes young and aged mice of both sexes to investigate the effects of sex and aging on adipose tissue mass and pro-inflammatory responses.

However, the author's studies suggest that efficient oxidative metabolism in older obese female adipose tissue compared to males combined with an active tissue remodeling state lead to this attenuated inflammatory response even with aging.

The Singer Research Team concluded in their Aging-US Research Paper, "Our studies demonstrate that aging and obesity in aging induce sexually dimorphic inflammatory responses owing to altered lipid metabolism and adipose tissue remodeling even with the same HFD exposure."

Full Text - https://doi.org/10.18632/aging.102438

Correspondence to: Luigi Ferrucci email: ksinger@med.umich.edu

Keywords: adipose tissue macrophages, aging, senescence, extracellular matrix remodeling, sex differences