FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue

Kathleen R Markan; Meghan C Naber; Sarah M Small; Lila Peltekian; Rachel L Kessler; Matthew J Potthoff

doi:10.1016/j.molmet.2017.03.009

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FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue

Journal article

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FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue

Kathleen R Markan, Meghan C Naber, Sarah M Small, Lila Peltekian, Rachel L Kessler and Matthew J Potthoff

Molecular metabolism (Germany), Vol.6(6), pp.602-610

06/2017

DOI: 10.1016/j.molmet.2017.03.009

PMCID: PMC5444074

PMID: 28580290

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Abstract

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to “FGF21 resistance” during the onset of diet-induced obesity. Here, we sought to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance and whether other mechanisms also contribute to FGF21 resistance in vivo. We generated adipose-specific β-klotho transgenic mice to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance in vivo. β-klotho protein levels are markedly decreased in white adipose tissue, but not liver or brown adipose tissue, during diet-induced obesity. Maintenance of β-klotho protein expression in adipose tissue does not alleviate impaired FGF21 signaling in white adipose or increase FGF21 sensitivity in vivo. In white adipose tissue, downregulation of β-klotho expression is not the major mechanism contributing to impaired FGF21 signaling in white adipose tissue.

Obesity

Resistance

Adipose

Betaklotho

FGF21

Details

Title: Subtitle: FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue
Creators: Kathleen R Markan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Meghan C Naber - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Sarah M Small - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Lila Peltekian - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Rachel L Kessler - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Matthew J Potthoff - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Molecular metabolism (Germany), Vol.6(6), pp.602-610
DOI: 10.1016/j.molmet.2017.03.009
PMID: 28580290
PMCID: PMC5444074
NLM abbreviation: Mol Metab
ISSN: 2212-8778
eISSN: 2212-8778
Publisher: Elsevier GmbH
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: K01DK111758, R01DK106104
Language: English
Date published: 06/2017
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040262402771

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