Fat browning and metabolic activation by oleanolic acid through β3-AR and p38 MAPK signaling
Obesity is a global health concern associated with metabolic diseases, highlighting the need for safer treatments. While anti-obesity drugs exist, their side effects have increased interest in natural compounds. Fat browning, the conversion of white to beige adipocytes, enhances energy expenditure via UCP1 and offers a promising strategy. Oleanolic acid (OA), a triterpenoid from olives, is known for its biological properties. This study examined fat browning effects of OA in 3T3-L1 adipocytes. OA reduced lipid droplet size and accumulation while increasing droplet number, as shown by Oil-Red-O staining. OA upregulated browning markers (UCP1, PGC-1α, PPARγ, C/EBPα) and transcription factors Cebpb and Prdm16. It also increased beige-specific genes (Cd137, Cidea, Cited1, Fgf21, Tbx1, Tmem26). Mitochondrial biogenesis genes (Cox4, Nrf1, Tfam) were elevated, and UCP1 expression was confirmed by immunofluorescence. Lipid metabolism improved through AMPK and ACC phosphorylation, reducing lipogenesis and increasing lipolytic genes (HSL, ATGL, PLIN, PKA). OA also enhanced fatty acid oxidation by upregulating Aco1, Cpt1, Ppara and promoting glycerol release. Mechanistically, OA activated β3-adrenergic receptor and p38 MAPK signaling. These findings suggest OA as a potential natural agent for obesity treatment via fat browning and metabolic regulation.
2025 Spring Convention