Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Mice With Dietary Obesity

Alexis M. Stranahan, De Huang Guo, Masaki Yamamoto, Caterina M. Hernandez, Hesam Khodadadi, Babak Baban, Wenbo Zhi, Yun Lei, Xinyun Lu, Kehong Ding, Carlos M. Isales

Research output: Contribution to journalArticlepeer-review

Abstract

Preferential energy storage in subcutaneous adipose tissue (SAT) confers protection against obesity-induced pathophysiology in females. Females also exhibit dis-tinct immunological responses, relative to males. These differences are often attributed to sex hormones, but reciprocal interactions between metabolism, immunity, and gonadal steroids remain poorly understood. We systematically characterized adipose tissue hypertro-phy, sex steroids, and inflammation in male and female mice after increasing durations of high-fat diet (HFD)– induced obesity. After observing that sex differences in adipose tissue distribution before HFD were correlated with lasting protection against inflammation in females, we hypothesized that a priori differences in the ratio of subcutaneous to visceral fat might mediate this rela-tionship. To test this, male and female mice underwent SAT lipectomy (LPX) or sham surgery before HFD chal-lenge, followed by analysis of glial reactivity, adipose tissue inflammation, and reproductive steroids. Because LPX eliminated female resistance to the proinflammatory effects of HFD without changing circulating sex hormones, we conclude that sexually dimorphic organization of subcutaneous and visceral fat determines susceptibility to inflammation in obesity.

Original languageEnglish (US)
Pages (from-to)245-260
Number of pages16
JournalDiabetes
Volume72
Issue number2
DOIs
StatePublished - Feb 2023

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint

Dive into the research topics of 'Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Mice With Dietary Obesity'. Together they form a unique fingerprint.

Cite this