WNT10B mutations in human obesity
Open Access
- 14 February 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetologia
- Vol. 49 (4), 678-684
- https://doi.org/10.1007/s00125-006-0144-4
Abstract
Aims/hypothesis Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. Subjects and methods We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. Results One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. Conclusions/interpretation These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.This publication has 20 references indexed in Scilit:
- THE WNT SIGNALING PATHWAY IN DEVELOPMENT AND DISEASEAnnual Review of Cell and Developmental Biology, 2004
- Wnt10b Inhibits Development of White and Brown Adipose TissuesJournal of Biological Chemistry, 2004
- Wnt proteins are lipid-modified and can act as stem cell growth factorsNature, 2003
- Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor GeneThe New England Journal of Medicine, 2003
- Regulation of Wnt Signaling during AdipogenesisOnline Journal of Public Health Informatics, 2002
- GSK‐3 inhibition by adenoviral FRAT1 overexpression is neuroprotective and induces Tau dephosphorylation and β‐catenin stabilisation without elevation of glycogen synthase activityFEBS Letters, 2001
- Potentiation of Glucose Uptake in 3T3-L1 Adipocytes by PPAR Agonists Is Maintained in Cells Expressing a PPAR Dominant-Negative Mutant: Evidence for Selectivity in the Downstream Responses to PPAR ActivationMolecular Endocrinology, 2001
- Inhibition of Adipogenesis by Wnt SignalingScience, 2000
- Transmembrane Tumor Necrosis Factor (TNF)-α Inhibits Adipocyte Differentiation by Selectively Activating TNF Receptor 1Journal of Biological Chemistry, 1999
- Undiagnosed Glucose Intolerance in the Community: the Isle of Ely Diabetes ProjectDiabetic Medicine, 1995