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

Table 1 Potential mechanisms and evidence to support a benefit for vitamin D in non-alcoholic fatty liver disease

Mechanisms	Evidence
Improvement in insulin secretion and insulin resistance	Presence of VDR in pancreatic beta cells[26]
	Expression of 1-α-hydroxylase enzyme in pancreatic beta cells[79]
	Impaired insulin secretory response in mice lacking a functional VDR[13]
	Transcriptional activation of the human insulin gene by 1,25(OH)2D[80]
	Vitamin D deficiency impairs glucose-mediated insulin secretion from rat pancreatic beta cells in vitro[81] and in vivo[82]
	Vitamin D enhances insulin responsiveness for glucose transport in muscle cells[83]
	Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization in adipocytes[44]
Improvement in adipose tissue inflammation	Higher 25(OH)D concentrations were independently associated with higher adiponectin concentrations in a large cohort of men and women[40]
	Reduction of IL-6 in adipocytes after supplementation of vitamin D in mice fed high fat diet[84]
	1,25-dihydroxyvitamin D treatment in human adipocytes inhibits NF-κB pathway and reduces pro-inflammatory cytokine release[85,86]
	1,25-dihydroxyvitamin D inhibits macrophage recruitment and increases adiponectin expression in preadipocytes[87]
Improvement in hepatic inflammation	Vitamin D deficiency causes TLR activation and exacerbates hepatic inflammation[42]
	Artificial sunlight therapy in rats reduced liver inflammation and apoptosis[43]
	VDR expression on cholangiocytes was inversely correlated with steatosis severity and nonalcoholic fatty liver disease score in NASH patients[31]
Improvement in hepatic fibrosis	Presence of VDR in HSC[24]
	Vitamin D treatment suppresses HSC proliferation in cultured HSC from rats[73]
	Vitamin D treatment downregulates pro-fibrotic marker TIMP-1 and collagen type I production in cultured HSCs[73,74]
	VDR knockout mice develop spontaneous liver injury with fibrosis[30]

VDR: Vitamin D receptor; TLR: Toll-like receptor; IL: Interleukin; TLR: Toll like receptor; NASH: Nonalcoholic steatohepatitis; HSC: Hepatic stellate cells.