Diet-induced
obesity is strongly associated with
nonalcoholic fatty-liver disease (
NAFLD) and
insulin resistance. We aimed to investigate the in vivo therapeutic value of
tetrahydrocurcumin (
THC) intervention in high-fat-diet (HFD)-induced
obesity and hepatic steatosis. C57BL/6 mice were fed an HFD for 10 weeks, and then they received 20 or 100 mg/kg
THC along with the HFD for another 10 weeks. Mice fed an HFD for 20 weeks experienced
obesity, hepatic steatosis,
hyperlipidemia, and
insulin resistance.
Tetrahydrocurcumin (
THC) intervention for 10 weeks significantly reduced adiposity (epididymal-fat weights of 6.6 ± 0.4 g for the HFD-only group and 5.3 ± 0.8 and 5.6 ± 0.7 g for the HFD with 20 mg/kg
THC and HFD with 100 mg/kg
THC groups, respectively; p < 0.05) via downregulation of adipogenic factors. Inflammatory macrophage infiltration and polarization were decreased by
THC in mouse epididymal adipose tissues. In the liver,
THC markedly alleviated steatosis by approximately 28-37% ( p < 0.05) via the downregulation of lipogenesis, the activation of
AMP-activated protein kinase (AMPK), and the increase of
fatty acid oxidation. Elevated
blood glucose and
insulin resistance were also improved by
THC, which might be caused by regulation of the hepatic
insulin signaling cascade, gene transcription involved in
glucose metabolism, and reduced macrophage infiltration in the liver and adipose tissue. Our results demonstrated the beneficial effects of
THC-mediated intervention against
obesity and
NAFLD as well as other
metabolic syndromes, revealing a novel
therapeutic use of
THC in obese populations.