Role of Foxa-2 in adipocyte metabolism and differentiation

Christian Wolfrum; David Q Shih; Satoru Kuwajima; Andrew W Norris; C Ronald Kahn; Markus Stoffel

doi:10.1172/JCI18698

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Role of Foxa-2 in adipocyte metabolism and differentiation

Journal article

Open access

Peer reviewed

Role of Foxa-2 in adipocyte metabolism and differentiation

Christian Wolfrum, David Q Shih, Satoru Kuwajima, Andrew W Norris, C Ronald Kahn and Markus Stoffel

The Journal of clinical investigation, Vol.112(3), pp.345-356

08/2003

DOI: 10.1172/JCI18698

PMCID: PMC166300

PMID: 12865419

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https://doi.org/10.1172/JCI18698View

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Abstract

Hepatocyte nuclear factors-3 (Foxa-1-3) are winged forkhead transcription factors that regulate gene expression in the liver and pancreatic islets and are required for normal metabolism. Here we show that Foxa-2 is expressed in preadipocytes and induced de novo in adipocytes of genetic and diet-induced rodent models of obesity. In preadipocytes Foxa-2 inhibits adipocyte differentiation by activating transcription of the Pref-1 gene. Foxa-2 and Pref-1 expression can be enhanced in primary preadipocytes by growth hormone, suggesting that the antiadipogenic activity of growth hormone is mediated by Foxa-2. In differentiated adipocytes Foxa-2 expression leads to induction of gene expression involved in glucose and fat metabolism, including glucose transporter-4, hexokinase-2, muscle-pyruvate kinase, hormone-sensitive lipase, and uncoupling proteins-2 and -3. Diet-induced obese mice with haploinsufficiency in Foxa-2 (Foxa-2+/-) develop increased adiposity compared with wild-type littermates as a result of decreased energy expenditure. Furthermore, adipocytes of these Foxa-2+/- mice exhibit defects in glucose uptake and metabolism. These data suggest that Foxa-2 plays an important role as a physiological regulator of adipocyte differentiation and metabolism.

3T3 Cells

Adipocytes - cytology

Adipocytes - metabolism

Animals

Base Sequence

Binding Sites - genetics

Cell Differentiation

DNA - genetics

DNA - metabolism

DNA-Binding Proteins - genetics

DNA-Binding Proteins - physiology

Glucose - metabolism

Hepatocyte Nuclear Factor 3-beta

Intercellular Signaling Peptides and Proteins

Membrane Proteins - genetics

Membrane Proteins - physiology

Mice

Mice, Inbred C57BL

Mice, Mutant Strains

Mice, Obese

Nuclear Proteins - genetics

Nuclear Proteins - physiology

Repressor Proteins - genetics

Repressor Proteins - physiology

Transcription Factors

Transcriptional Activation

Details

Title: Subtitle: Role of Foxa-2 in adipocyte metabolism and differentiation
Creators: Christian Wolfrum - Rockefeller University
David Q Shih
Satoru Kuwajima
Andrew W Norris
C Ronald Kahn
Markus Stoffel
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.112(3), pp.345-356
DOI: 10.1172/JCI18698
PMID: 12865419
PMCID: PMC166300
ISSN: 0021-9738
eISSN: 1558-8238
Grant note: R01 DK055033 / NIDDK NIH HHS GM07739 / NIGMS NIH HHS R01 DK55033-04 / NIDDK NIH HHS T32 GM007739 / NIGMS NIH HHS
Language: English
Date published: 08/2003
Academic Unit: Endocrinology and Diabetes; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
Record Identifier: 9984293074902771

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