TY - JOUR
T1 - Sex Differences in Adipose Tissue Distribution Determine Susceptibility to Neuroinflammation in Mice With Dietary Obesity
AU - Stranahan, Alexis M.
AU - Guo, De Huang
AU - Yamamoto, Masaki
AU - Hernandez, Caterina M.
AU - Khodadadi, Hesam
AU - Baban, Babak
AU - Zhi, Wenbo
AU - Lei, Yun
AU - Lu, Xinyun
AU - Ding, Kehong
AU - Isales, Carlos M.
N1 - Publisher Copyright:
© 2023 by the American Diabetes Association.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
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U2 - 10.2337/db22-0192
DO - 10.2337/db22-0192
M3 - Article
C2 - 36367881
AN - SCOPUS:85147045240
SN - 0012-1797
VL - 72
SP - 245
EP - 260
JO - Diabetes
JF - Diabetes
IS - 2
ER -