2074-LB: Metabolic Heterogeneity of Adipocytes during Obesity Revealed by Single Nucleus RNA-seq

Objective: The prevalence of obesity continues increasing nowadays, but the understanding on the pathogenesis of obesity and its complications remains obscure. Adipocytes are the main components of metabolic homeostasis, involved in glucose and lipid metabolism, hormone and adipokine secretion. Previous studies show that adipocytes manifest high heterogeneity within white adipose tissue (WAT). Obesity changes the living environment of adipocytes. Thus, to investigate the potential impact of adipocytes metabolic changes towards obesity-related metabolic disorder, we explored the metabolic features of adipocytes through single nucleus RNA-seq (snRNA-seq) data and patients under bariatric surgery. Methods: The snRNA-seq data of WAT from patients across a range of body weight were obtained from the GEO database, and genes related to metabolic pathways were extracted from the genome. Using single-cell data reduction and clustering tools to explore the metabolic signatures of adipocytes and cellular function. In addition, the differences in metabolic pathways of adipocytes and the expression levels of molecular targets were verified in other publicly available bulk RNA-seq data and WAT of patients undergoing bariatric surgery in our clinical center. Results: 1) Human white adipocytes can be divided into 13 subgroups with unique metabolic signatures by snRNA-seq clustering. 2) Adipocytes enriched in the “cofactors and vitamins metabolism” were decreased, and the lipid hormone metabolic adipocytes increased in individuals with obesity. 3) The signatures of “cofactors and vitamins metabolism” showed positive correlation with the activity of leptin response pathway. Conclusion: Human white adipocyte subgroups manifest high metabolic diversification within WAT of individuals across a range of body weight. Our study suggests that the "cofactors and vitamins metabolism" might be a potential therapeutic strategy for treating obesity. Disclosure Y. Chen: None.