FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance.
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.
Cederberg
A
A
Medical Genetics, Department of Medical Biochemistry, Göteborg University, Box 440, SE-405 30, Göteborg, Sweden.
Grønning
L M
LM
Ahrén
B
B
Taskén
K
K
Carlsson
P
P
Enerbäck
S
S
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001823:Body Composition; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004032:Diet; D004789:Enzyme Activation; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D007527:Isoenzymes / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D010101:Oxygen Consumption; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D007527:Isoenzymes; D008055:Lipids; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases