title: Nonalcoholic fatty liver disease and reduced serum vitamin D(3) levels.
abstract: Nonalcoholic fatty liver disease (NAFLD) and vitamin D3 deficiency are two highly prevalent pathologic conditions worldwide that share several cardiometabolic risk factors. In addition to its traditional calcium-related effects on the skeleton, vitamin D3 deficiency has now been recognized to exert nonskeletal adverse effects on several other organ systems. Accumulating epidemiological evidence suggests that low levels of serum 25-hydroxyvitamin D3 are associated with the presence and severity of NAFLD, independently of several potential confounders, including features of the metabolic syndrome. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a hepato-protective role for the active metabolite of vitamin D3. 1α,25-dihydroxyvitamin D3 modulates the insulin signaling pathway/insulin resistance, suppresses fibroblast proliferation and collagen production, exerts anticoagulant and profibrinolytic effects, and modulates macrophage activity and inflammatory cytokine generation. Overall, the high prevalence of vitamin D3 deficiency and the plausible biological mechanisms linking this to NAFLD suggest that treatment of vitamin D3 deficiency to prevent and/or treat NAFLD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D3 supplementation could have any potential benefit in reducing the development and progression of NAFLD.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. giovanni.targher@univr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Targher
authors.forename: Eleonora
authors.initials: E
authors.lastname: Scorletti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mantovani
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Byrne
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002762:Cholecalciferol / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D005234:Fatty Liver / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease; D012307:Risk Factors; D015398:Signal Transduction; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000453:epidemiology
chemical_list: D001647:Bile Acids and Salts; D007155:Immunologic Factors; D002762:Cholecalciferol