α‐ and γ‐Tocopherol protect against lipopolysaccharide (LPS) induced hepatic injury in leptin deficient obese mice

Abstract

Hepatic steatosis is an obesity‐triggered fatty liver disease in which the liver becomes vulnerable to oxidative insults resulting in nonalcoholic steatohepatitis (NASH). We hypothesized that α‐ or γ‐tocopherol (α‐ or γ‐T) supplementation during hepatic steatosis would decrease the progression towards LPS‐induced NASH. Five‐wk old obese (ob/ob) and lean littermate mice were fed a control, α‐T, or γ‐T supplemented diet (1000 mg/kg) for 5 wk (18 mice/genotype/diet) and then injected with LPS prior to sacrifice at 0, 1.5 or 6 h. Obese compared to lean mice had ∼40% greater (p<0.05) body weight and >3‐times hepatic lipid which were unaffected by Ts or LPS. Obese compared to lean mice had greater hepatic Ts. T supplementation further increased hepatic α‐ and γ‐T by 9.7 and 10.1‐times respectively, compared to respective obese controls. LPS reduced hepatic Ts at 6 h compared to 0 and 1.5 h in obese mice. Obese mice had higher serum alanine aminotransferase (ALT) and α‐ and γ‐T supplementation in obese mice similarly reduced LPS‐induced increases in ALT at 1.5 and 6 h. α‐ and γ‐T supplementation decreased hepatic ascorbic acid (AA) in obese mice and LPS increased AA at 6 h. These data suggest that α‐ or γ‐T protected against LPS‐induced hepatic injury in obese mice likely through a common mechanism not involving AA. Additional study is underway to define the protective mechanism of T supplementation against NASH.