FRI020 Adipocyte Subpopulations Regulate Growth Hormone-induced Lipolysis And Insulin Resistance

Abstract

Abstract Disclosure: S. Siyar: None. J. Huang: None. R. Sharma: None. J.J. Kopchick: None. V. Puri: None. K.Y. Lee: None. Growth Hormone (GH) administration has long been known to increase lipolysis in adipose tissue leading to increased circulating free fatty acid levels and insulin resistance. Previous studies from our lab have found that this effect is mediated, at least in part, through transcriptional repression of the lipid droplet associated protein Fat specific protein (FSP27 also known as CIDEC). Furthermore, recent studies suggest that within a single adipose tissue depot there are different subpopulations of adipocytes. We have identified three distinct subpopulations of adipocytes with unique gene expression profiles and metabolic activities. We have found that one of these subpopulations of adipocytes, termed Type 2 adipocytes, are highly responsive to GH stimulation. In order to assess the physiological role of GH-mediated lipolysis mediated by this subpopulation, we specifically expressed human FSP27 (hFSP27) in Type 2 adipocytes (Type2Ad-hFSP27tg mice). Type2AdhFSP27tg mice had reduced systemic plasma glycerol release after acute GH treatment, and improvement in acute, but not chronic, GH-induced glucose intolerance. These mice exhibited an 45% increase in fat mass and significant increase in adipocyte cell size further indicating a decreased lipolytic response to GH. This decreased lipolytic response was associated with improved hepatic insulin signaling and insulin-induced gene expression in Type2Ad-hFSP27tg mice. Taken together, these results indicate that specifically targeting a subpopulation of adipocytes is sufficient to reduce GH-induced lipolysis and insulin resistance and may provide a platform for improved medical therapies for growth and endocrine disorders. Presentation: Friday, June 16, 2023