Shedding new light on vitamin D and fatty liver disease

Abstract

Vitamin D in its active form, 1,25-(OH)2 vitamin D, has been shown to play a role in various diseases, such as different types of infectious and autoimmune diseases as well as cancers [1]. It is estimated that one billion people worldwide are vitamin D deficient or insufficient [2]. Sources of vitamin D are diet and dietary supplements as well as endogenously synthesised vitamin D from 7-dehydrocholesterol following exposure to ultraviolet B radiation [1]. To achieve the biologically active form, vitamin D3 undergoes 25-hydroxylation in the liver and subsequent 1hydroxylation in the kidneys [3]. Meanwhile vitamin D has been reported to control over 200 genes in a direct or indirect way. Among those are genes regulating angiogenesis, apoptosis, cell growth, proliferation and differentiation [4], mainly reducing cell proliferation and inducing terminal differentiation [4,5]. Furthermore, immunomodulatory effects of 1,25-(OH)2 vitamin D are well described, as monocytic cells upregulate vitamin D receptor upon antigen exposure, enhancing innate immune responses. In this view, vitamin D may also favour immune tolerance towards the liver allograft as early vitamin D supplementation in patients post-transplantation was associated with a reduced rate of acute cellular rejection [6]. In the view of bile acid-dependent uptake of vitamin D and its hepatic metabolism, it is reasonable to expect an association between vitamin D status and both cholestatic and non-cholestatic chronic liver disease. Indeed, serum concentrations of 1,25-(OH)2 vitamin D are decreased in patients with cirrhosis versus noncirrhotic patients [7,8] and a gradual decline has been observed in cirrhotic patients according to increasing Child-Pugh class [7] and clinical decompensation [9]. Recently, a significant correlation between lower 25-OH vitamin D levels and an increasing stage of fibrosis and severity of necroinflammatory activity was observed in a population with genotype 1 chronic hepatitis C [10]. Interestingly, reduced 25-OH vitamin D levels can be found in patients with non-alcoholic fatty liver disease (NAFLD) compared to controls with a close association to the histological severity of hepatic steatosis, necroinflammation and fibrosis [11]. Since in this study 25-OH vitamin D was inversely associated with NAFLD features independent of insulin resistance