LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion
Data(s) |
03/02/2015
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Resumo |
Summary 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. © 2015 The Authors. |
Formato |
application/pdf |
Identificador | |
Publicador |
Cell Press |
Relação |
http://eprints.qut.edu.au/94197/1/94197_pubVersion.pdf DOI:10.1016/j.cmet.2015.01.009 Loh, Nellie Y., Neville, Matt J., Marinou, Kyriakoula, Hardcastle, Sarah A., Fielding, Barbara A., Duncan, Emma L., McCarthy, Mark I., Tobias, Jonathan H., Gregson, Celia L., Karpe, Fredrik, & Christodoulides, Constantinos (2015) LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion. Cell Metabolism, 21(2), pp. 262-272. |
Direitos |
Copyright 2015 The Authors |
Fonte |
Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #beta catenin #insulin #low density lipoprotein receptor related protein 5 #abdominal obesity #adipocyte #adipogenesis #adipose derived stem cell #adult #anthropometry #Article #body fat #body fat distribution #bone mass #cell differentiation #cell immortalization #cell proliferation #controlled study #ex vivo study #female #gain of function mutation #gene expression #human #human experiment #human tissue #intraabdominal fat #lipid storage #male #normal human #priority journal #protein function #regulatory mechanism #Wnt signaling pathway |
Tipo |
Journal Article |