306-LB: Adipocyte Subpopulations Mediate the Inflammatory Response in Adipose Tissue

Abstract

Recent studies suggest that, even within a single adipose depot, there may be distinct subpopulations of adipocytes. Our lab has uncovered three developmentally distinct subpopulations of white adipocytes. These adipocyte subpopulations have unique gene expression signatures, and display differential responses to exogenous stimuli including insulin, inflammatory cytokines, and insulin. These three adipocyte subtypes are distinguished by high expression of specific marker genes: Wilms’ tumor 1 (type 1), transgelin (type 2), and myxovirus 1 (type 3). Utilizing Cre transgenic mice, transcription of which is directed by the promoters of these marker genes, lineage tracing analysis indicate that these three preadipocyte subpopulations independently gave rise to adipocytes in vivo, and differentially contribute to the adipose tissue depots. During high fat diet (HFD) induced obesity, macrophages, organized into crown like structures (CLS) around dead and dying adipocytes, are detected in the vicinity of type 1 adipocytes, as assessed by kernel density estimation. This association between type 1 adipocytes and CLS is secondary to a ∼10-fold increase in the expression of macrophage chemoattractant protein 1 at both the mRNA and protein level. Furthermore, although CLS are found in the vicinity of type 1 cells, with very few of the CLS are in direct contact with type 1 adipocytes. Instead, over 80% of CLS are found in direct contact with type 2 adipocytes, indicating an increased death of these adipocytes during HFD-induced obesity. Taken together, these data suggest that type 1 and type2 adipocytes coordinately regulate the inflammatory response in adipose tissue. Disclosure Q. Luong: None. J. Huang: None. R. Sharma: None. K.Y. Lee: None. Funding American Diabetes Association (1-17-JDF-055 to K.Y.L.)