FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance

A Cederberg; L M Grønning; B Ahrén; K Taskén; P Carlsson; S Enerbäck

doi:10.1016/s0092-8674(01)00474-3

FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance

Cell. 2001 Sep 7;106(5):563-73. doi: 10.1016/s0092-8674(01)00474-3.

Authors

A Cederberg¹, L M Grønning, B Ahrén, K Taskén, P Carlsson, S Enerbäck

Affiliation

¹ Medical Genetics, Department of Medical Biochemistry, Göteborg University, Box 440, SE-405 30, Göteborg, Sweden.

PMID: 11551504
DOI: 10.1016/s0092-8674(01)00474-3

Abstract

Obesity, hyperlipidemia, and insulin resistance are common forerunners of type 2 diabetes mellitus. We have identified the human winged helix/forkhead transcription factor gene FOXC2 as a key regulator of adipocyte metabolism. Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene expression, which leads to a lean and insulin sensitive phenotype. FOXC2 affects adipocyte metabolism by increasing the sensitivity of the beta-adrenergic-cAMP-protein kinase A (PKA) signaling pathway through alteration of adipocyte PKA holoenzyme composition. Increased FOXC2 levels, induced by high fat diet, seem to counteract most of the symptoms associated with obesity, including hypertriglyceridemia and diet-induced insulin resistance--a likely consequence hereof would be protection against type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / metabolism*
Adipose Tissue / drug effects
Adipose Tissue / metabolism
Adipose Tissue / ultrastructure
Adrenergic beta-Agonists / pharmacology
Adult
Animals
Blood Glucose / metabolism
Blotting, Northern
Body Composition
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / chemistry
Cyclic AMP-Dependent Protein Kinases / metabolism
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism*
Diet
Enzyme Activation
Forkhead Transcription Factors
Gene Expression
Gene Expression Regulation
Genes, Reporter
Humans
Hypertriglyceridemia / genetics*
Hypertriglyceridemia / metabolism
Insulin / blood
Insulin Resistance / genetics*
Isoenzymes / metabolism
Lipids / blood
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Obesity / genetics*
Obesity / metabolism
Organ Size
Oxygen Consumption
Transcription Factors / genetics*
Transcription Factors / metabolism*

Substances

Adrenergic beta-Agonists
Blood Glucose
DNA-Binding Proteins
Forkhead Transcription Factors
Insulin
Isoenzymes
Lipids
Transcription Factors
mesenchyme fork head 1 protein
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases