Vitamin D improves hepatic steatosis in NAFLD via regulation of fatty acid uptake and β-oxidation

Abstract

IntroductionThe study aimed to explore the association of serum 25(OH)D3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway.MethodsThe study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro, HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot.ResultsNAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D3. VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD.ConclusionThe study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.

Vitamin D3 exacerbates steatosis while calcipotriol inhibits inflammation in non-alcoholic fatty liver disease in Sod1 knockout mice: a comparative study of two forms of vitamin D

“…Interventions with 500–1000 IU per kg body weight of VD 3 mitigated liver fat accumulation induced by HFD in rats. 36,37 A preventive treatment with a diet containing 10 000 U kg −1 of VD 3 reduced liver fat accumulation in C57BL/6 mice, but interventional VD 3 had no evident effect. 38 However, the findings of Bozic et al support our experimental results, showing an increase in hepatic Vdr mRNA expression in ApoE knockout mice induced by HFD and those on a methionine and choline-deficient (MCD) diet; meanwhile, VDR knockout could reverse early-stage NAFLD steatosis.…”

Effects of plant natural products on metabolic-associated fatty liver disease and the underlying mechanisms: a narrative review with a focus on the modulation of the gut microbiota

“…The biological roles of VD include not only maintaining the balance of calcium and phosphorus metabolism in the body and participating in bone reconstruction but also reducing insulin resistance, modulating immunity, protecting cardiovascular health, and exerting antifibrosis and anti-inflammation effects ( Chun et al., 2019 ; Whiting and Calvo, 2021 ). Numerous epidemiological investigations have shown that VD deficiency is closely associated with MAFLD, cirrhosis and obesity, and there is also evidence that VD has a protective effect against MAFLD ( Tian et al., 2020 ; Du et al., 2023 ; Barchetta et al., 2011 ; Ciardullo et al., 2023 ; Barchetta et al., 2020 ; Barchetta et al., 2017 ; Pop et al., 2022 ). Furthermore, VD supplementation can alter the abundance and diversity of the gut microbiota.…”