FRI021 Adipocyte Subpopulations Regulate The Lipolytic Response And Inflammatory Cytokine Action In Obesity

Disclosure: J. Huang: None. R. Sharma: None. K.Y. Lee: None. Previously, our lab has utilized gene expression profiling and lineage tracing analysis to uncover three developmentally and functionally distinct subpopulations of white adipocytes with stable and unique gene expression profiles, which were termed Type 1, 2, and 3 adipocytes, respectively. This study extends these findings to investigate the role of Type 2 adipocytes in obesity. We found that the proportion of Type 2 preadipocytes and adipocytes in each adipose tissue was stable through time, but was dynamically regulated by high-fat diet (HFD) induced obesity in a depot-specific manner with a 59.34% increase in the perigonadal fat depots. Histological examination of fat depots after HFD-induced obesity revealed that over 80% of recruited macrophages, organized into crown-like structures, were found in direct contact with Type 2 adipocytes indicating increased necrosis or apoptosis of this adipocyte subpopulation. In addition, treatment of macrophage-derived inflammatory cytokine TNFα increased lipolysis specifically in Type 2 adipocytes by 11.9%, with no effects on other adipocytes. As previous studies have shown that inflammatory cytokines promote lipolysis in adipose tissue, at least in part, through the reduction of FSP27 (fat specific protein 27), we assessed the contribution of Type 2 adipocytes by overexpressing FSP27 specifically in this population (Type2Ad-hFSP27tg mice) during the development of obesity. We found that HFD-fed male Type2Ad-hFSP27tg mice had improved glucose tolerance and insulin sensitivity, with no change in body weight. These metabolic changes may, at least in part, be explained by the reduced basal and stimulated lipolysis rate in the visceral fat of Type2Ad-hFSP27tg mice compared with control mice. Although over-expression of FSP27 in primary Type 2 adipocytes is sufficient to acutely reduce TNFα-induced apoptosis, no reduction of macrophage infiltration was found in HFD-fed Type2Ad-hFSP27tg visceral fat after 18 weeks of HFD. Taken together, these results strongly suggest that adipocyte subpopulations contribute to the regulation of obesity-associated inflammation and lipolytic response in adipose tissue. Presentation: Friday, June 16, 2023