Sex-Dependent Role of Adipose Tissue HDAC9 in Diet-Induced Obesity and Metabolic Dysfunction

Brandee Goo, Samah Ahmadieh, Abdalrahman Zarzour, Nicole K.H. Yiew, David Kim, Hong Shi, Jacob Greenway, Stephen Cave, Jenny Nguyen, Swetha Aribindi, Mark Wendolowski, Praneet Veerapaneni, Mourad Ogbi, Weiqin Chen, Yun Lei, Xin Yun Lu, Ha Won Kim, Neal L. Weintraub

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Obesity is a major risk factor for both metabolic and cardiovascular disease. We reported that, in obese male mice, histone deacetylase 9 (HDAC9) is upregulated in adipose tissues, and global deletion of HDAC9 protected against high fat diet (HFD)-induced obesity and metabolic disease. Here, we investigated the impact of adipocyte-specific HDAC9 gene deletion on diet-induced obesity in male and female mice. The HDAC9 gene expression was increased in adipose tissues of obese male and female mice and HDAC9 expression correlated positively with body mass index in humans. Interestingly, female, but not male, adipocyte-specific HDAC9 KO mice on HFD exhibited reduced body weight and visceral adipose tissue mass, adipocyte hypertrophy, and improved insulin sensitivity, glucose tolerance and adipogenic differentiation gene expression. Furthermore, adipocyte-specific HDAC9 gene deletion in female mice improved metabolic health as assessed by whole body energy expenditure, oxygen consumption, and adaptive thermogenesis. Mechanistically, compared to female mice, HFD-fed male mice exhibited preferential HDAC9 expression in the stromovascular fraction, which may have offset the impact of adipocyte-specific HDAC9 gene deletion in male mice. These results suggest that HDAC9 expressed in adipocytes is detrimental to obesity in female mice and provides novel evidence of sex-related differences in HDAC9 cellular expression and contribution to obesity-related metabolic disease.

Original languageEnglish (US)
Article number2698
JournalCells
Volume11
Issue number17
DOIs
StatePublished - Sep 2022

Keywords

  • HDAC9
  • high fat diet
  • insulin resistance
  • obesity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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