Vitamin D: a new player in non-alcoholic fatty liver disease?

Abstract

Vitamin D through its active form 1a-25-dihydroxyvtamin D [1,25(OH)2D] is a secosteroid hormone that plays a key role in mineral metabolism. Recent years have witnessed a significant scientific interest on vitamin D and expanded its actions to include immune modulation, cell differentiation and proliferation and inflammation regulation. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency has become one of the most prevalent micronutrient deficiencies worldwide. Concomitantly, non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in western countries. NAFLD and vitamin D deficiency often coexist and epidemiologic evidence has shown that both of these conditions share several cardiometabolic risk factors. In this article we provide an overview of the epidemiology and pathophysiology linking NAFLD and vitamin D deficiency, as well as the available evidence on the clinical utility of vitamin D supplementation in NAFLD.

Keywords: Fatty liver; Non-alcoholic fatty liver disease; Steatohepatitis; Vitamin D.

Figure 1

Vitamin D synthesis and metabolism. DBP: D binding protein; VDRE: Vitamin D response element.

Figure 2

Schematic representation of metabolic, anti-inflammatory and anti-fibrotic effects of vitamin D on hepatocytes and non-parenchymal hepatic cells (hepatic stellate cells, Kupffer cells) in non-alcoholic fatty liver disease. Left: At the initial stage of lipogenesis, 1,25(OH)₂D acts on adipocytes and inhibits NF-κB transcription, known as the pro-inflammatory “master switch”, and thus inhibits the expression of the inflammatory cytokines IL-6, TNF-α and IL-1β. It also increases adiponectin secretion from adipoycytes and enhances GLUT-4 receptor expression in myocytes, both of which improve insulin resistance; Middle: Increased gut permeability allows translocation of bacterial pathogens which can activate Toll like receptors on Kupffer cells. 1,25(OH)₂D downregulates the expression of TLR-2, TLR-4 and TLR-9 in these cells and thus ameliorates inflammation; Right: 1,25(OH)₂D acts on hepatic stellate cells by binding to VDR and reduces proliferation of these cells that play a major role in inducing fibrosis. VDR: Vitamin D receptor; TLR: Toll like receptor; LPS: Lipopolysacharides.