The nature of sex differences in catecholamine-induced lipolysis in subcutaneous fat cells

Women demonstrate a more efficient energy metabolism than men, which is important for sex differences in metabolic health. This dimorphism involves a greater capacity to mobilize lipids from adipose tissue through triglyceride lipolysis following catecholamine stimulation. Herein, we examined the cellular nature of this dimorphism of catecholamine action in human adipocytes from subcutaneous adipose tissue by combining extensive pharmacological experiments with descriptive proteome and transcriptome analyses in large cohorts. We observed two sex-dependent differences in catecholamine-stimulated adipocyte lipolysis: in women, the lipolytic sensitivity (half maximum effective hormone concentration) was 50% decreased, involving increased coupling of antilipolytic alpha-2A adrenoceptors to adenylyl cyclase. However, the maximum lipolytic hormone effect was 50% increased and linked to more efficient mono- and triacylglycerol lipases. Treatment targeting adipocyte lipolysis might be used in men to diminish sex differences in the regulation of lipid metabolism.