title: Changes in FGF21 serum concentrations and liver mRNA expression in an experimental model of complete lipodystrophy and insulin-resistant diabetes.
abstract: Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Prague, Czech Republic. zelezna@uochb.cas.cz.
authors.forename: A
authors.initials: A
authors.lastname: Spolcová
authors.forename: M
authors.initials: M
authors.lastname: Holubová
authors.forename: B
authors.initials: B
authors.lastname: Mikulášková
authors.forename: V
authors.initials: V
authors.lastname: Nagelová
authors.forename: A
authors.initials: A
authors.lastname: Stofková
authors.forename: Z
authors.initials: Z
authors.lastname: Lacinová
authors.forename: J
authors.initials: J
authors.lastname: Jurčovičová
authors.forename: M
authors.initials: M
authors.lastname: Haluzík
authors.forename: L
authors.initials: L
authors.lastname: Maletínská
authors.forename: B
authors.initials: B
authors.lastname: Zelezná
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1