Curcumin, recognized for its antioxidant and anti-inflammatory properties, is a promising dietary supplement for liver protection. However, its role in preventing obesity-induced hepatic steatosis is not fully understood. This study aims to show that curcumin mitigates hepatic steatosis and promotes browning and thermogenesis in white adipose tissue (WAT) under obesity. Male C57BL/6 mice were assigned to four groups: standard diet (STD), STD supplemented with 100 mg/kg curcumin, high-fat diet (HFD), or HFD supplemented with 100 mg/kg curcumin, administered for 4 weeks. Compared to STD mice, HFD-fed mice exhibited significantly greater body weight, epididymal fat mass, liver weight, postprandial blood glucose (PBG), insulin, and plasma/hepatic alanine aminotransferase (ALT) and triglyceride (TG) levels, alongside an inflammatory response and macrophage infiltration. Additionally, HFD-fed mice showed reduced adiponectin, adiponectin receptor-1, and PI3K/AKT phosphorylation in liver tissue. Except for liver weight, these effects were reversed in curcumin-treated HFD mice. Curcumin inhibited adipocyte hypertrophy and elevated the expression of PGC-1α, PPARγ, and UCP-1 proteins, as well as Zic1, Prdm16, Tnfrsf9, and Tmem26 genes in epididymal fat pads (EFPs). It also significantly altered gut microbiota composition, reducing pro-inflammatory bacteria such as Helicobacter, Oscillospira, Parabacteroides, and Alistipes, thereby alleviating intestinal dysbiosis and improving obesity-related metabolic parameters. In conclusion, curcumin's protective effects against hepatic steatosis and adiposity in HFD-fed mice stem from its ability to upregulate adiponectin, enhance insulin signaling, promote WAT browning, increase thermogenesis, and modulate intestinal dysbiosis.
