Dieckol suppresses lipid accumulation and promotes thermogenic markers in 3T3-L1 adipocytes via ERK/p38 MAPK signaling.

Thermogenic programming of adipocytes represents a promising strategy to enhance energy expenditure; however, most pharmacological browning agents activate PPARγ, which simultaneously promotes lipid accumulation and adipocyte hypertrophy. This study aimed to investigate whether dieckol induces thermogenic markers during adipocyte differentiation under conditions of restrained adipogenic commitment and to elucidate the involvement of MAPK and Nrf2 signaling pathways. 3T3-L1 preadipocytes were differentiated in the presence of dieckol (5-25 µM). Lipid accumulation, lipolytic activity, and intracellular reactive oxygen species were assessed using Oil Red O staining, enzymatic assays, and fluorescence analysis. Protein expression and signaling pathway activation were evaluated by Western blotting using pharmacological inhibitors of ERK1/2 (PD98059) and p38 MAPK (SB203580). Dieckol increased the expression of PRDM16, PGC-1α, and UCP1 while concurrently suppressing PPARγ, C/EBPα, and lipogenic marker expression, resulting in reduced intracellular triglyceride and cholesterol accumulation. Dieckol also enhanced lipolytic signaling and glycerol release, activated ERK1/2- and p38-dependent MAPK signaling, and promoted nuclear translocation of Nrf2 with increased activities of SOD, GPx, and CAT. Inhibition of MAPK signaling, particularly ERK1/2, attenuated dieckol-induced thermogenesis-associated modulation and lipid metabolic regulation. In conclusion, dieckol promotes thermogenic markers in differentiating 3T3-L1 adipocytes through coordinated ERK/p38 MAPK and Nrf2 signaling, enhancing UCP1 expression and lipolysis while suppressing lipid accumulation and adipogenic markers.