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The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function
Author(s) -
Carli Jayne F. Martin,
LeDuc Charles A.,
Zhang Yiying,
Stratigopoulos George,
Leibel Rudolph L.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701216r
Subject(s) - medicine , endocrinology , adipocyte , biology , adipose tissue , cilium , gene knockdown , microbiology and biotechnology , gene , genetics
Genetic variants within the FTO (α‐ketoglutarate‐dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator‐interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l +/ − mice exhibit increased adiposity, in part, as a result of hyperphagia. Here, we describe the effects of Rpgrip1l in adipocytes that may contribute to the adiposity phenotype observed in these animals and possibly in humans who segregate for FTO risk alleles. Loss of Rpgrip1l in 3T3‐L1 preadipocytes increased the number of cells that are capable of differentiating into mature adipocytes. Knockout of Rpgrip1l in mature adipocytes using Adipoq‐Cre did not increase adiposity in mice that were fed chow or a high‐fat diet. We also did not observe any effects of Rpgrip1l knockdown in mature 3T3‐L1 adipocytes. Thus, to the extent that Rpgrip1l affects cell‐autonomous adipose tissue function, it may do so as a result of the effects conveyed in preadipocytes in which the primary cilium is functionally important. We propose that decreased RPGRIP1L expression in preadipocytes in humans who segregate for FTO obesity risk alleles may increase the storage capacity of adipose tissue.—Martin Carli, J. F., LeDuc, C. A., Zhang, Y., Stratigopoulos, G., Leibel, R. L. The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function. FASEB J. 32, 3946–3956 (2018). www.fasebj.org