Changes in FGF21 Serum Concentrations and Liver mRNA Expression in an Experimental Model of Complete Lipodystrophy and Insulin-Resistant Diabetes

0434081 - ÚOCHB 2015 RIV CZ eng J - Journal Article
Špolcová, Andrea - Holubová, Martina - Mikulášková, Barbora - Nagelová, Veronika - Štofková, A. - Lacinová, Z. - Jurčovičová, J. - Haluzík, M. - Maletínská, Lenka - Železná, Blanka
Changes in FGF21 Serum Concentrations and Liver mRNA Expression in an Experimental Model of Complete Lipodystrophy and Insulin-Resistant Diabetes.
Physiological Research. Roč. 63, č. 4 (2014), s. 483-490. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576
Institutional support: RVO:61388963
Keywords : FGF21 * A-ZIP mice * lipodystrophy * insulin resistance * fatty liver * GLUT-1
Subject RIV: CE - Biochemistry
Impact factor: 1.293, year: 2014

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.
Permanent Link: http://hdl.handle.net/11104/0238388