Depot- and sex-specific differences in human leptin mRNA expression - Implications for the control of regional fat distribution

Montague, CT, Prins, JB, Sanders, L, Digby, JE and ORahilly, S (1997) Depot- and sex-specific differences in human leptin mRNA expression - Implications for the control of regional fat distribution. Diabetes, 46 3: 342-347. doi:10.2337/diabetes.46.3.342


Author Montague, CT
Prins, JB
Sanders, L
Digby, JE
ORahilly, S
Title Depot- and sex-specific differences in human leptin mRNA expression - Implications for the control of regional fat distribution
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
Publication date 1997-03-01
Year available 1997
Sub-type Article (original research)
DOI 10.2337/diabetes.46.3.342
Open Access Status DOI
Volume 46
Issue 3
Start page 342
End page 347
Total pages 6
Publisher AMER DIABETES ASSOC
Language eng
Abstract Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders.
Keyword Obese Gene-Expression
Adipose-Tissue
Messenger-Rna
Body-Weight
Ob Protein
Women
Rats
Metabolism
Cloning
Mouse
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 20000
PG/12/78/29862
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 428 times in Thomson Reuters Web of Science Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 23 Nov 2013, 04:18:24 EST by System User