Mechanistic insights into resolvin D5's anti-obesity effects: Suppression of lipid droplet accumulation via adipogenesis inhibition, lipolysis induction, and energy metabolism enhancement in 3 T3-L1 cells

Obesity, characterized by excessive lipid accumulation and metabolic dysregulation, requires effective therapeutic strategies. This study investigates the anti-obesity effects of resolvin D5 (RvD5) in 3 T3-L1 adipocytes. RvD5 treatment during differentiation (D0-D8) significantly reduced lipid droplet and triglyceride accumulation in a dose-dependent manner, with notable effects at 20 μg/ml and 30 μg/ml. RvD5 suppressed adipogenesis during the early differentiation stage (D0-D2) by upregulating β-catenin, which downregulated the expression of PPARγ and CEBPα. Knockdown of β-catenin abolished these effects, underscoring its pivotal role. Additionally, RvD5 promoted lipolysis during the intermediate and late stages (D2-D8), as evidenced by increased glycerol release, upregulation of ATGL, HSL, and LC3-II, and downregulation of perilipin-1 and p62. RvD5 further enhanced energy metabolism by upregulating β3-AR, p-AMPK/AMPK, PGC-1α, UCP2, and CPTI, contributing to the reduction in lipid accumulation. These findings highlight the potential of RvD5 as a promising therapeutic candidate for obesity management. • RvD5 inhibits the accumulation of lipid droplets and triglycerides in 3 T3-L1 cells. • RvD5 inhibits adipogenesis in 3 T3-L1 cells. • RvD5 activates lipolysis in 3 T3-L1 cells. • RvD5 enhances energy metabolism in 3 T3-L1 cells.