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PMID: 15155905 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nuclear receptor corepressor RIP140 regulates fat accumulation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 22 ·2004-06-01 ·Pages 8437-42

Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, Bell J, So PW, Medina-Gomez G, Vidal-Puig A, White R, Parker MG

Abstract

Nuclear receptors and their coactivators have been shown to function as key regulators of adipose tissue biology. Here we show that a ligand-dependent transcriptional repressor for nuclear receptors plays a crucial role in regulating the balance between energy storage and energy expenditure. Mice devoid of the corepressor protein RIP140 are lean, show resistance to high-fat diet-induced obesity and hepatic steatosis, and have increased oxygen consumption. Although the process of adipogenesis is unaffected, expression of certain lipogenic enzymes is reduced. In contrast, genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1, are markedly increased. Therefore, the maintenance of energy homeostasis requires the action of a transcriptional repressor in white adipose tissue, and ligand-dependent recruitment of RIP140 to nuclear receptors may provide a therapeutic target in the treatment of obesity and related disorders.

MeSH Terms
Adaptor Proteins, Signal Transducing Adipocytes/cytology,metabolism Adipose Tissue/cytology,metabolism Animals Biomarkers Body Weight Cell Differentiation/physiology Cells, Cultured Dietary Fats Energy Metabolism Fibroblasts/cytology,metabolism Gene Expression Regulation Liver/cytology,metabolism,pathology Magnetic Resonance Imaging Mice Mice, Inbred C57BL Nuclear Proteins/metabolism Nuclear Receptor Interacting Protein 1 Obesity/metabolism Phenotype Repressor Proteins/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Biomarkers Dietary Fats Nuclear Proteins Nuclear Receptor Interacting Protein 1 Repressor Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Leonardsson Göran
Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London W12 ONN, United Kingdom.
Steel Jenny H
Christian Mark
Pocock Victoria
Milligan Stuart
Bell Jimmy
So Po-Wah
Medina-Gomez Gema
Vidal-Puig Antonio
White Roger
Parker Malcolm G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401013101
Published
2004-06-01
Epub
2004-00-20
Pages
8437-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC420412
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0401013101 PMC Full Text View journal details
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