Tetrahydrocurcumin ameliorates metabolic disorders associated with obesity by regulating gut microbiota homeostasis

Obesity, a global health crisis, demands novel therapeutic strategies. Tetrahydrocurcumin (THC), a natural compound, shows promise in mitigating obesity by regulating gut microbiota and lipid metabolism. Using in vitro (Hepa1-6 cells) and in vivo (C. elegans and HFD C57BL/6 J mice) models, we evaluated THC's effects on lipid accumulation, oxidative stress, and key metabolic markers. In glucose-induced obese C. elegans, THC reduced lipid deposition and enhanced antioxidant capacity. In HFD mice, THC improved hepatic function (reduced AST/ALT), decreased liver fat content, and lowered oxidative stress. Mechanistically, THC downregulated Stearoyl-CoA desaturase-1 (SCD1) and Diacylglycerol O acyltransferase 1 (DGAT1) expression (Western blot/RT-qPCR), pivotal regulators of lipid metabolism. Fecal 16S rRNA sequencing revealed THC-modulated gut microbiota, including reduced Firmicutes/Bacteroidetes ratio and Desulfobacterota abundance, alongside elevated short-chain fatty acids (SCFAs). In vitro, THC suppressed lipid accumulation in Hepa1-6 cells. Collectively, THC alleviates obesity by targeting lipid metabolism, oxidative stress, and gut microbial homeostasis, highlighting its therapeutic potential.