Active form of vitamin D ameliorates non-alcoholic fatty liver disease by alleviating oxidative stress in a high-fat diet rat model

[摘要] The purpose of this study was to determine whether treatment using the active form of vitamin D (1,25(OH)2D3) could protect against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats and ameliorate oxidative stress.Male Sprague-Dawley rats were divided into three groups and treated with standard chow, HFD, or HFD plus intraperitoneal injection of 1,25(OH)2D3 (5 μg/kg body weight, twice per week), respectively, for 16 weeks.Serum lipid profiles, hepatic function, intrahepatic lipid, and calcium levels were determined.Hepatic histology was examined using hematoxylin/eosin, Masson’s trichrome, and Oil Red O staining.Oxidative stress was assessed by measuring hepatic malondialdehyde (MDA) and F2α-isoprostane content.Expression of nuclear factor-erythroid-2-related factor 2 (Nrf2) and downstream target genes was analyzed using quantitative RT-PCR.1,25(OH)2D3 treatment improved the serum lipid profile, reduced intrahepatic lipid levels, and attenuated hepatic steatosis and inflammation in HFD rats.Furthermore, MDA and F2α-isoprostane levels in liver tissue were reduced by 1,25(OH)2D3 administration.Although 1,25(OH)2D3 did not regulate the expression of Nrf2 mRNA, it did induce Nrf2 nuclear translocation.The expression of Nrf2 target genes, including Gclc, Nqo1, Sod2, and Cat, was up-regulated by 1,25(OH)2D3.We conclude that 1,25(OH)2D3 protects against HFD-induced NAFLD by attenuating oxidative stress, inducing NRF2 nuclear translocation, and up-regulating the expression of genes encoding antioxidant enzymes.

[学科分类] 内分泌与代谢学

[关键词] Calcitriol;Non-alcoholic fatty liver disease;Nuclear factor-erythroid-2-related factor 2;Oxidative stress