EPA promotes fatty acid storage and thermogenic capacity in primary differentiated mouse subcutaneous adipocytes

Abstract

Adipose tissue dysfunction has been associated with lipid dysregulation and insulin resistance. Compared with visceral fat, subcutaneous adipose tissue has been recently emerged as a lipid storage and thermogenic depot, playing a beneficial role in lipid homeostasis and insulin resistance. N‐3 PUFAs are known to have a role against hyperlipidemia and insulin resistance. Herein, we determined if EPA promotes beneficial metabolic activities of subcutaneous adipocytes. Primary stromal‐vascular (SV) cells isolated from mouse inguinal adipose tissue were cultured and induced to differentiate into adipocytes. EPA was added to SV cell culture during differentiation. On day 8 of differentiation, glucose metabolism, fatty acid storage, and thermogenic capacity were assessed. When compared to controls, EPA‐treated subcutaneous adipocytes had increased levels of basal glucose uptake and GLUT4 mRNA expression, but decreased glucose and lactate levels in the cultured media, suggesting decreased glycolysis. To assess fatty acid storage capacity, lipolysis, fatty acid uptake, and TAG synthesis were determined. We observed that EPA‐treated adipocytes had significantly decreased glycerol release and downregulation of HSL and ATGL gene expression, while markedly increased expression of genes involved in fatty acid uptake, CD36 and TAG synthesis, GPAT1 and GPAT3. Moreover, EPA treatment led to a significant increase in the expression of thermogenic genes including PGC1α, COXiv, UCP1, UCP2 and UCP3 as well as adiponectin expression. We conclude that EPA enhances fatty acid storage and energy dissipation capacity in subcutaneous adipocytes, contributing in part to its metabolic benefits.Grant Funding Source: NIH