Abstract:Objective To explore the mechanism by which docosahexaenoic acid ( DHA) inhibits the accumulation of adipose tissue lipid in high-fat diet ( HFD)-induced body weight gain in C57BL/ 6 mice. Methods Animals were fed a control diet (C57BL/ 6 C group), a 45% HFD (C57BL/ 6 H group) or 45% HFD with 0. 2 g DHA (FAD3C) or 0. 4 g DHA (FAD3H) per g of food for 20 weeks. Resting metabolic rate was measured at 19 weeks. Visceral adipose and brown adipose tissue were collected for RNA extraction. Lipogenesis-related and fat browning-related gene expression was detected by quantitative PCR. Results A HFD significantly increased (P < 0. 05) body weight, body fat, and serum leptin and triglyceride ( TG) levels in the C57BL/ 6 H group compared with the C57BL/ 6 C group. DHA significantly decreased (P < 0. 05) body weight, fat mass, and levels of serum leptin and TG in the FAD3C and FAD3H groups compared with the C57BL/ 6 H group. In visceral adipose tissue, DHA significantly downregulated the expression of lipogenesis-related genes, including the CCAAT/ enhancer-binding protein, peroxisome proliferator-activated receptor-γ, and sterol regulatory element-binding protein-1C in FAD3H groups compared with the C57BL/ 6 C group (P < 0. 05). In visceral adipose and brown adipose tissue, DHA supplementation significantly increased (P < 0. 05) the expression of fat browning-related genes, including uncoupling protein 1, and peroxisome proliferator-activated receptor coactivator-1a in FAD3H groups compared with the C57BL/ 6 H group. Conclusions DHA may be used to combat obesity by regulating the resting metabolic rate, levels of leptin, fat and TG, and the expression of browning-related and lipogenesis-related genes.