Celastrol alleviates high-fat diet-induced hepatic steatosis in wild type mice. Celastrol improves anti-inflammatory and antioxidant status in wild type mice. Celastrol induces the expression of hepatic Sirt1 in wild type mice. Celastrol promotes AMPKα phosphorylation in liver specific Sirt1-deficient mice. Celastrol increases the activity of NFκB in liver specific Sirt1-deficient mice.