Metabolic Regulation by Fibroblast Growth Factor 21
type: CreativeWork
description: Fibroblast growth factor 21 (FGF21) is a secreted hormone that can beneficially regulate glucose and lipid homeostasis. Through a reverse endocrinology approach, we uncovered that FGF21 expression is transcriptionally regulated by the peroxisome proliferator activated-receptor alpha (PPARa) in liver. PPARa is a member of the nuclear hormone receptor superfamily that is physiologically activated by increased fatty acid mobilization to liver during fasting, and regulates the genetic program whereby lipids are converted to ketone bodies through a process known as ketogenesis. Here, I show the effects of FGF21 as a fasting hormone that is expressed in liver and contributes to the regulation of adipose tissue and hepatic ketogenesis during the fasted state. Using in vitro and in vivo methods to investigate the effects of FGF21, a model whereby FGF21 stimulates lipolysis in adipose tissue was generated. Intriguingly, using our FGF21 transgenic mice, I observed the expression of many genes involved in lipogenesis was highly induced in adipose tissue in an FGF21-dependent manner. Moreover, many of these lipogenic genes were found to be down-regulated in adipose of the FGF21 knockout mouse. The inhibition of lipogenic genes in adipose tissue was associated with increased SUMOylation of PPARg protein in this tissue. Using a feeding-fasting paradigm, I found that FGF21 expression in the liver and adipose tissue was rhythmic, peaking in liver prior to feeding and peaking in the adipose after feeding. Furthermore, the induction of FGF21 by PPARg ligands suggested a unique function for this protein in adipose, independent from its role in the fasted state. To assess the contribution of FGF21 to the anti-diabetic properties of PPARg agonists (ie. thiazolidinediones), diet-induced obese wild type and Fgf21-/- mice were treated with the TZD rosiglitazone. Rosiglitazone produced a significant increase in adipose FGF21 expression, but decreased hepatic FGF21 mRNA and circulating FGF21…
abstract: Fibroblast growth factor 21 (FGF21) is a secreted hormone that can beneficially regulate glucose and lipid homeostasis. Through a reverse endocrinology approach, we uncovered that FGF21 expression is transcriptionally regulated by the peroxisome proliferator activated-receptor alpha (PPARa) in liver. PPARa is a member of the nuclear hormone receptor superfamily that is physiologically activated by increased fatty acid mobilization to liver during fasting, and regulates the genetic program whereby lipids are converted to ketone bodies through a process known as ketogenesis. Here, I show the effects of FGF21 as a fasting hormone that is expressed in liver and contributes to the regulation of adipose tissue and hepatic ketogenesis during the fasted state. Using in vitro and in vivo methods to investigate the effects of FGF21, a model whereby FGF21 stimulates lipolysis in adipose tissue was generated. Intriguingly, using our FGF21 transgenic mice, I observed the expression of many genes involved in lipogenesis was highly induced in adipose tissue in an FGF21-dependent manner. Moreover, many of these lipogenic genes were found to be down-regulated in adipose of the FGF21 knockout mouse. The inhibition of lipogenic genes in adipose tissue was associated with increased SUMOylation of PPARg protein in this tissue. Using a feeding-fasting paradigm, I found that FGF21 expression in the liver and adipose tissue was rhythmic, peaking in liver prior to feeding and peaking in the adipose after feeding. Furthermore, the induction of FGF21 by PPARg ligands suggested a unique function for this protein in adipose, independent from its role in the fasted state. To assess the contribution of FGF21 to the anti-diabetic properties of PPARg agonists (ie. thiazolidinediones), diet-induced obese wild type and Fgf21-/- mice were treated with the TZD rosiglitazone. Rosiglitazone produced a significant increase in adipose FGF21 expression, but decreased hepatic FGF21 mRNA and circulating FGF21…
author: Dutchak, Paul Anthony
language: en
keywords: Fibroblast Growth Factor, Liver, Peroxisome Proliferator-Activated Receptors
date published: 2011-12-13T02:04:32Z
date modified: 2026-07-24T05:52:34Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/935