Improved hepatic γ-tocopherol status limits oxidative and inflammatory stress-mediated liver injury in db/db mice with nonalcoholic steatohepatitis. (January 2018)

• Record Type: Journal Article
• Authors: Dey, Priyankar; Mah, Eunice; Li, Jinhui; Jalili, Thunder; Symons, J. David; Bruno, Richard S.
• Is Part Of: Journal of functional foods. Volume 40(2018)
• Page Start: 670
• Page End: 678
• Publication Date: 2018-01
• Subjects: Diabetes -- Gamma-tocopherol -- iNOS -- Insulin resistance -- Lipid peroxidation -- Nonalcoholic steatohepatitis; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2017.12.007
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: γ-T supplementation increase hepatic γ-T and γ-CEHC in db/db mice with NASH. γ-T improves ALT and insulin resistance without affecting insulin sensitivity. Hepatic lipid peroxidation was lowered independent of Nrf2 expression. Hepatic inflammation (iNOS, MCP-1, CRP) was lowered by γ-T treatment. γ-T mitigates NASH through antioxidant and antiinflammatory activities. Abstract: γ-Tocopherol (γ-T) and its physiological metabolite γ-carboxyethyl-hydroxychroman (γ-CEHC) exhibit antioxidant and anti-inflammatory activities. We hypothesized that improved hepatic γ-T status would protect against NASH in leptin-resistant db/db mice. Wild-type mice were fed a diet without γ-T, and db/db mice were fed the same diet supplemented with or without γ-T for 8 wk. Hepatic γ-T and γ-CEHC levels were increased ( P < .05) compared with db/db controls. Serum ALT and insulin resistance, which were otherwise increased in db/db controls, were 33–38% lower in db/db mice fed γ-T. Increased hepatic lipid peroxidation in db/db mice was attenuated by dietary γ-T, which occurred without increasing hepatic Nrf2 mRNA expression. However, γ-T attenuated hepatic iNOS, MCP-1, TNF-α and CRP expression. Histological assessment showed γ-T-mediated improvements in overall hepatic architecture, specifically by limiting hepatic steatosis. These findings demonstrate that improvements in hepatic γ-T status protect against liver injury during NASH by reducing inflammation and oxidative stress.