Protective effect of alpha-tocopherol on lipogenesis and oxysterol production in hypercholesterolemia-induced nonalcoholic Steatohepatitis


Sahin A., Demirel-Yalciner T., Sozen E., Ozer N. K.

Free Radical Research, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1080/10715762.2024.2421173
  • Dergi Adı: Free Radical Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Nonalcoholic steatohepatitis, oxysterols, fatty acids, alpha-tocopherol
  • Marmara Üniversitesi Adresli: Evet

Özet

Despite limited number of studies, oxysterols are known to contribute to the progression of nonalcoholic steatohepatitis (NASH) by affecting lipid/cholesterol metabolism and elevating proinflammatory and profibrotic processes. Accordingly, we used a high cholesterol-mediated in vivo NASH model and aimed to determine alterations in fatty acid content and oxysterol levels together with their effects on cholesterol/lipid metabolism during the progression of the disease. We further investigated the beneficial role of α-tocopherol. To this end, in our hypercholesterolemic rabbit model, we determined fatty acid profile by GC–MS while 25-, 27-, 4β-, 7α, and 24(S)-Hydroxycholesterol levels by means of LC–MS/MS. Additionally, lipid (SREBP-1c, PPARα, PPARγ) and cholesterol metabolism-related proteins (LXRα, SREBP2 and ABCA1) were determined by immunoblotting. In conclusion, the present findings provide a complete analysis of the hepatic alterations in lipid and oxysterol profiles mediated by a high-cholesterol diet. In addition, this study explains the protective effect of α-tocopherol on lipogenesis and oxysterol production in hypercholesterolemia-induced NASH. We believe that present study will guide to novel theories in the progression and therapeutic targeting of fatty liver diseases.