Eicosapentaenoic acid promotes thermogenic and fatty acid storage capacity in mouse subcutaneous adipocytes

In this study, we determined if eicosapentaenoic acid (EPA) promotes beneficial metabolic activities of subcutaneous adipocytes. Stromal-vascular (SV) cells were isolated from inguinal adipose tissue of C57BL/6 mice and induced to differentiate into adipocytes. EPA effect on thermogenic and mitochondrial gene expression and oxidative metabolism were assessed in inguinal adipocytes. When added to SV cell cultures during 8 day differentiation, EPA significantly increased the expression of thermogenic genes UCP1-3, CIDEA and VEGFα. Moreover, EPA increased mitochondrial DNA content and the expression of genes involved in mitochondrial biogenesis including PGC1α, Nrf1 and COXiv. However, this effect was not perceived when EPA was added to mature inguinal adipocytes for 24 h, suggesting that EPA exerts its browning effect via recruiting brite adipocytes. Consistently, long-term EPA treatment also upregulated AMPKα phosphorylation and CPT1 expression and increased glucose uptake and GLUT4 mRNA expression, suggesting improved mitochondrial oxidation. Additionally, EPA-treated adipocytes had enlarged lipid droplets and increased expression of triglyceride synthesis genes GPAT1 and GPAT3, while significantly decreased glycerol release and down-regulation of HSL and ATGL gene expression. We conclude that EPA enhances energy dissipation capacity by recruiting brite adipocytes to stimulate oxidative metabolism and reduces fatty acid release by facilitating fatty acid storage in subcutaneous adipocytes.