271-LB: Assessment of P311's Influence on Key Genetic Signatures within Brown Adipose Tissue

Abstract

The dramatic ascent in global obesity levels > 40% has ushered in an alarming increase in chronic metabolic illnesses such as insulin resistance, type 2 diabetes, and cardiovascular disease all for which obesity is a major risk factor. This development has created a need for a deeper understanding of the molecular underpinnings which regulate this interplay between obesity and metabolic homeostasis. Our studies show that P311 can modulate adipocyte development, plasticity and there by regulating metabolic function. Novel single cell RNA technology using the 10X platform was performed to assess key adipogenic and metabolic gene signatures. Single cells collected from brown adipose tissue of C57BL/6 control mice (WT) and P311 KO mice were used for RNA sequencing. Bioinformatic analysis using the Seurat package in R evaluated the cellular heterogeneity found in brown adipose tissue, including immune cells, preadipocytes, and beige adipocytes. Marker genes were employed to identify and characterize these distinct cell populations. Visualization using UMAP showed the significant alteration of cluster identities between WT and P311 KO tissue. Our findings showed a significant decrease (p<0.01) in key brown adipocyte signatures in P311 KO brown adipocytes compared to WT brown adipocytes. We observed a tremendous decrease of browning in brown adipocytes switching them to more whitish brown adipocytes in P311KOs compared to WT that could be responsible for deranged metabolic alterations in P311KOs. We conclude that P311 regulates browning of adipocytes there by regulating metabolic homeostasis. Disclosure S. L. Moreton: None. M. R. Aluru: None. K. R. Badri: None. Funding National Institute of General Medical Sciences (SC1GM141937 to K.R.B.)