Document Detail


Hypomorphism for RPGRIP1L, a Ciliary Gene Vicinal to the FTO Locus, Causes Increased Adiposity in Mice.
MedLine Citation:
PMID:  24807221     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Common polymorphisms in the first intron of FTO are associated with increased body weight in adults. Previous studies have suggested that a CUX1-regulatory element within the implicated FTO region controls expression of FTO and the nearby ciliary gene, RPGRIP1L. Given the role of ciliary genes in energy homeostasis, we hypothesized that mice hypomorphic for Rpgrip1l would display increased adiposity. We find that Rpgrip1l(+/-) mice are hyperphagic and fatter, and display diminished suppression of food intake in response to leptin administration. In the hypothalamus of Rpgrip1l(+/-) mice, and in human fibroblasts with hypomorphic mutations in RPGRIP1L, the number of AcIII-positive cilia is diminished, accompanied by impaired convening of the leptin receptor to the vicinity of the cilium, and diminished pStat3 in response to leptin. These findings suggest that RPGRIP1L may be partly or exclusively responsible for the obesity susceptibility signal at the FTO locus.
Authors:
George Stratigopoulos; Jayne F Martin Carli; Diana R O'Day; Liheng Wang; Charles A Leduc; Patricia Lanzano; Wendy K Chung; Michael Rosenbaum; Dieter Egli; Daniel A Doherty; Rudolph L Leibel
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell metabolism     Volume:  19     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-05-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  767-79     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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