![]() Additionally, FGF21 improved the diabetic phenotypes of these animals by decreasing hyperglycemia, hyperinsulinemia, glucose intolerance, and increasing peripheral and hepatic insulin sensitivity. In these different models, FGF21 reduced body weight, plasma and hepatic cholesterol and triglycerides levels, and increased oxygen consumption. Recombinant FGF21 therapy corrected many metabolic perturbations in diseased rodent models and non-human primates. ![]() Pharmacologically, FGF21 has become recognized as a modulator of glucose and lipid homeostasis in vivo. ![]() In response to fasting or a ketogenic diet, FGF21 expression is induced primarily in the liver through the action of PPARα. It is expressed predominantly in liver, white and brown adipose tissues (WAT & BAT) and pancreas. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.įibroblast growth factor 21 (FGF21) regulates energy homeostasis in mammals. gave permission to publish.Ĭompeting interests: All authors are employees and own shares in Amgen Inc. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: Amgen Inc. Received: FebruAccepted: JPublished: July 6, 2012Ĭopyright: © 2012 Véniant et al. PLoS ONE 7(7):Įditor: Britta Siegmund, Charité-Universitätsmedizin Berlin, Germany (2012) FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice. Together these data suggest that adipose tissue is required for the triglyceride and glucose, but not the cholesterol lowering efficacy of FGF21, and that leptin and FGF21 exert additive anti-diabetic effects in Tg mice.Ĭitation: Véniant MM, Hale C, Helmering J, Chen MM, Stanislaus S, Busby J, et al. Impaired FGF21-induced signaling indicated that residual adipose tissue of Tg mice was resistant to FGF21, whilst normal FGF21 signaling was observed in Tg livers. Molecular analyses of Tg mice revealed normal adipose expression of Fgfr1, Klb and an 8-fold over-expression of Fgf21. Further, leptin treatment alone was sufficient to restore the anti-diabetic effects of rmuFGF21 in Tg mice. After transplantation, FGF21 responsiveness was completely restored in WAT transplanted Tg mice compared to sham Tg mice. To determine if adipose mass was critical for these effects, we transplanted WT white adipose tissue (WAT) into Tg mice and treated the mice with rmuFGF21. Unlike wildtype (WT) mice, Tg mice were refractory to the beneficial effects of rmuFGF21 on body weight, adipose mass, plasma insulin and glucose tolerance. To delineate if adipose tissue is the predominant organ responsible for anti -diabetic effects of FGF21, we treated mice with reduced body fat (lipodystrophy mice with adipose specific expression of active sterol regulatory element binding protein 1c Tg) with recombinant murine FGF21 (rmuFGF21). Fibroblast growth factor 21 (FGF21) is a potent metabolic regulator, and pharmacological administration elicits glucose and lipid lowering responses in mammals.
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