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

Cederberg A ¹,

Grønning LM ,

Ahrén B ,

Taskén K ,

Carlsson P ,

Enerbäck S

Affiliations

1. Medical Genetics, Department of Medical Biochemistry, Göteborg University, Box 440, SE-405 30, Göteborg, Sweden.
Authors
Cederberg A¹
(1 author)

ORCIDs linked to this article

Cell, 01 Sep 2001, 106(5):563-573
https://doi.org/10.1016/s0092-8674(01)00474-3 PMID: 11551504

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.

Full text links

Read article at publisher's site: https://doi.org/10.1016/s0092-8674(01)00474-3

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S0092867401004743/pdf

References

Articles referenced by this article (43)

Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children.
Abbott WG, Foley JE
Metabolism, (6):576-579 1987
MED: 3295474
Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.
Boden G
Diabetes, (1):3-10 1997
MED: 8971073
The response to long-term overfeeding in identical twins.
Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Theriault G, Dussault J, Moorjani S, Pinault S, Fournier G
N Engl J Med, (21):1477-1482 1990
MED: 2336074
Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes.
Christy RJ, Yang VW, Ntambi JM, Geiman DE, Landschulz WH, Friedman AD, Nakabeppu Y, Kelly TJ, Lane MD
Genes Dev, (9):1323-1335 1989
MED: 2606350
Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels.
Coe NR, Simpson MA, Bernlohr DA
J Lipid Res, (5):967-972 1999
MED: 10224167
Genetically lean mice result from targeted disruption of the RII beta subunit of protein kinase A.
Cummings DE, Brandon EP, Planas JV, Motamed K, Idzerda RL, McKnight GS
Nature, (6592):622-626 1996
MED: 8757131
Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3',5'-cyclic phosphorothioates.
Dostmann WR, Taylor SS, Genieser HG, Jastorff B, Doskeland SO, Ogreid D
J Biol Chem, (18):10484-10491 1990
MED: 2162349
Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cis-regulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis.
Enerback S, Ohlsson BG, Samuelsson L, Bjursell G
Mol Cell Biol, (10):4622-4633 1992
MED: 1406652
Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese.
Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kozak LP
Nature, (6628):90-94 1997
MED: 9139827
Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism.
Fajas L, Schoonjans K, Gelman L, Kim JB, Najib J, Martin G, Fruchart JC, Briggs M, Spiegelman BM, Auwerx J
Mol Cell Biol, (8):5495-5503 1999
MED: 10409739

Show 10 more references (10 of 43)

Citations & impact

Impact metrics

373

Citations

Jump to Citations

Data citations

Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/3380203

Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/3380203

Article citations

Adipokines in the Crosstalk between Adipose Tissues and Other Organs: Implications in Cardiometabolic Diseases.
Hemat Jouy S, Mohan S, Scichilone G, Mostafa A, Mahmoud AM
Biomedicines, 12(9):2129, 19 Sep 2024
Cited by: 0 articles | PMID: 39335642 | PMCID: PMC11428859
Review
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Identification of potential tissue-specific biomarkers involved in pig fat deposition through integrated bioinformatics analysis and machine learning.
Yang Y, Li M, Zhu Y, Wang X, Chen Q, Lu S
Heliyon, 10(10):e31311, 15 May 2024
Cited by: 1 article | PMID: 38807889 | PMCID: PMC11130688
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming.
Holman CD, Sakers AP, Calhoun RP, Cheng L, Fein EC, Jacobs C, Tsai L, Rosen ED, Seale P
Elife, 12:RP87756, 22 May 2024
Cited by: 13 articles | PMID: 38775132 | PMCID: PMC11111218
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
β-Adrenergic Signal and Epigenomic Regulatory Process for Adaptive Thermogenesis.
Matsumura Y, Osborne TF, Ito R, Takahashi H, Sakai J
Adv Exp Med Biol, 1461:213-227, 01 Jan 2024
Cited by: 0 articles | PMID: 39289284
Review
CDK6 is essential for mesenchymal stem cell proliferation and adipocyte differentiation.
Hu AJ, Li W, Pathak A, Hu GF, Hou X, Farmer SR, Hu MG
Front Mol Biosci, 10:1146047, 16 Aug 2023
Cited by: 0 articles | PMID: 37664186 | PMCID: PMC10469316
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC

Go to all (373) article citations

Other citations

Wikipedia

https://en.wikipedia.org/wiki/FOXC2

Data

Data that cites the article

This data has been provided by curated databases and other sources that have cited the article.

The Rat Genome Database (RGD) was established in 1999 and rapidly became the premier site for genetic, genomic, phenotype, and disease-related data generated from rat research. In addition, RGD has expanded to include a large body of structured and standardized data for eight species (rat, mouse, human, chinchilla, bonobo, 13-lined ground squirrel, dog and pig). Much of this data is the result of manual curation work by RGD curators. In other instances, it has been imported into RGD from other databases through custom ELT (Extract, Load and Transform) pipelines giving RGD users integrated access to a wide variety of data to support their research efforts. RGD also offers a growing suite of innovative tools for querying, analyzing and visualizing this data making it a valuable resource for researchers worldwide. (2)

Search life-sciences literature (45,104,206 articles, preprints and more)

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

Author information