Title |
LRP5 Regulates Human Body Fat Distribution by Modulating Adipose Progenitor Biology in a Dose- and Depot-Specific Fashion
|
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Published in |
Cell Metabolism (Science Direct), February 2015
|
DOI | 10.1016/j.cmet.2015.01.009 |
Pubmed ID | |
Authors |
Nellie Y. Loh, Matt J. Neville, Kyriakoula Marinou, Sarah A. Hardcastle, Barbara A. Fielding, Emma L. Duncan, Mark I. McCarthy, Jonathan H. Tobias, Celia L. Gregson, Fredrik Karpe, Constantinos Christodoulides |
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. |
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Country | Count | As % |
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United States | 3 | 30% |
United Kingdom | 3 | 30% |
Netherlands | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
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Members of the public | 5 | 50% |
Scientists | 5 | 50% |
Mendeley readers
Geographical breakdown
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United States | 1 | <1% |
China | 1 | <1% |
Unknown | 111 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 22 | 19% |
Researcher | 17 | 15% |
Professor > Associate Professor | 9 | 8% |
Student > Bachelor | 8 | 7% |
Other | 6 | 5% |
Other | 20 | 18% |
Unknown | 31 | 27% |
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Medicine and Dentistry | 23 | 20% |
Agricultural and Biological Sciences | 19 | 17% |
Social Sciences | 3 | 3% |
Engineering | 2 | 2% |
Other | 7 | 6% |
Unknown | 31 | 27% |