title: Hepatokines: unlocking the multi-organ network in metabolic diseases.
abstract: In the face of urbanisation, surplus energy intake, sedentary habits and obesity, type 2 diabetes has developed into a major health concern worldwide. Commonly overlooked in contemporary obesity research, the liver is emerging as a central regulator of whole body energy homeostasis. Liver-derived proteins known as hepatokines are now considered attractive targets for the development of novel type 2 diabetes treatments. This commentary presents examples of three leading hepatokines: fetuin-A, the first to be described and correlated with increased inflammation and insulin resistance; angiopoietin-like protein (ANGPTL)8/betatrophin, initially proposed for its action on beta cell proliferation, although this effect has recently been brought into question; and fibroblast growth factor 21 (FGF21), an insulin-sensitising hormone that is an appealing drug target because of its beneficial metabolic actions. Novel discoveries in hepatokine research may lead to promising biomarkers and treatments for metabolic disorders and type 2 diabetes. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).
authors.affiliation: Inserm U1016 Institut Cochin, 24 rue du Faubourg Saint Jacques, 75014, Paris, France.
authors.forename: Alison
authors.initials: A
authors.lastname: Iroz
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Couty
authors.forename: Catherine
authors.initials: C
authors.lastname: Postic
mesh_terms: D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008659:Metabolic Diseases / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D036361:Peptide Hormones; D060749:alpha-2-HS-Glycoprotein; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors