The metabolic coregulator RIP140: an update

Fritah, Asmaà; Christian, Mark; Parker, Malcolm G.

doi:10.1152/ajpendo.00243.2010

Cited by 67 publications

(68 citation statements)

References 37 publications

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“…Previous data indicated that RIP140 is a ubiquitously expressed transcription factor (16). By quantitative real-time quantitative PCR (qPCR) analysis, Rip140 mRNA was detected in all the mouse tissues tested and particularly in the intestine and colon (Supplemental Figure 1A; supplemental material available online with this article; doi:10.1172/ JCI65178DS1).…”

Section: Rip140 Expression In the Intestinal Epitheliummentioning

confidence: 97%

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis

Lapierre¹,

Bonnet²,

Bascoul-Mollevi³

et al. 2014

J. Clin. Invest.

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Deregulation of the Wnt/APC/β-catenin signaling pathway is an important consequence of tumor suppressor APC dysfunction. Genetic and molecular data have established that disruption of this pathway contributes to the development of colorectal cancer. Here, we demonstrate that the transcriptional coregulator RIP140 regulates intestinal homeostasis and tumorigenesis. Using Rip140-null mice and mice overexpressing human RIP140, we found that RIP140 inhibited intestinal epithelial cell proliferation and apoptosis. Interestingly, following whole-body irradiation, mice lacking RIP140 exhibited improved regenerative capacity in the intestine, while mice overexpressing RIP140 displayed reduced recovery. Enhanced RIP140 expression strongly repressed human colon cancer cell proliferation in vitro and after grafting onto nude mice. Moreover, in murine tissues and human cancer cells, RIP140 stimulated APC transcription and inhibited β-catenin activation and target gene expression. Finally, RIP140 mRNA and RIP140 protein levels were decreased in human colon cancers compared with those in normal mucosal tissue, and low levels of RIP140 expression in adenocarcinomas from patients correlated with poor prognosis. Together, these results support a tumor suppressor role for RIP140 in colon cancer.

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Section: Rip140 Expression In the Intestinal Epitheliummentioning

confidence: 97%

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis

Lapierre¹,

Bonnet²,

Bascoul-Mollevi³

et al. 2014

J. Clin. Invest.

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“…It has been found that RIP140 binds and represses a number of nuclear receptors, including peroxisome proliferator-activated receptors and estrogen-related receptors (17). Substantial evidence has indicated that RIP140 acts as a corepressor in adipose and skeletal muscle to control the state of adiposity (41), as well as muscle fiber types and metabolism (55).…”

Section: R380 Clenbuterol Reduces Mitochondrial Substrate Oxidationmentioning

confidence: 99%

Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle

Hoshino

Yoshida

Holloway

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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a ␤2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 302: R373-R384, 2012. First published November 9, 2011 doi:10.1152/ajpregu.00183.2011.-Clenbuterol, a ␤2-adrenergic agonist, reduces mitochondrial content and enzyme activities in skeletal muscle, but the mechanism involved has yet to be identified. We examined whether clenbuterol-induced changes in the muscles' metabolic profile and the intrinsic capacity of mitochondria to oxidize substrates are associated with reductions in the nuclear receptor coactivator PGC-1 alpha and/or an increase in the nuclear corepressor RIP140. In rats, clenbuterol was provided in the drinking water (30 mg/l). In 3 wk, this increased body (8%) and muscle weights (12-17%). In red (R) and white (W) muscles, clenbuterol induced reductions in mitochondrial content (citrate synthase: R, 27%; W, 52%; cytochrome-c oxidase: R, 24%; W, 34%), proteins involved in fatty acid transport (fatty acid translocase/CD36: R, 36%; W, 35%) and oxidation [␤-hydroxyacyl CoA dehydrogenase (␤-HAD): R, 33%; W, 62%], glucose transport (GLUT4: R, 8%; W, 13%), lactate transport monocarboxylate transporter (MCT1: R, 61%; W, 37%), and pyruvate oxidation (PDHE1␣, R, 18%; W, 12%). Concurrently, only red muscle lactate dehydrogenase activity (25%) and MCT4 (31%) were increased. Palmitate oxidation was reduced in subsarcolemmal (SS) (R, 30%; W, 52%) and intermyofibrillar (IMF) mitochondria (R, 17%; W, 44%) along with reductions in ␤-HAD activity (SS: R, 17%; W, 51%; IMF: R, 20%; W, 57%). Pyruvate oxidation was only reduced in SS mitochondria (R, 20%; W, 28%), but this was not attributable solely to PDHE1␣, which was reduced in both SS (R, 21%; W, 20%) and IMF mitochondria (R, 15%; W, 43%). These extensive metabolic changes induced by clenbuterol were associated with reductions in PGC-1␣ (R, 37%; W, 32%) and increases in RIP140 (R, 23%; W, 21%). This is the first evidence that clenbuterol appears to exert its metabolic effects via simultaneous and reciprocal changes in the nuclear receptor coactivator PGC-1␣ and the nuclear corepressor RIP140. mitochondria; oxidative capacity CLENBUTEROL, A ␤2-ADRENERGIC agonist, induces skeletal and cardiac muscle hypertrophy, due to increased protein synthesis and a concomitant decrease in protein degradation in this tissue (2,46,50). This ␤2-adrenergic agonist is a commonly prescribed bronchodilator treatment for asthmatic patients, while its anabolic properties have led to its illegal use in animal meat production and doping in sports. Nevertheless, it has been found that the treatment with this clenbuterol provoked deleterious effects on the cardiovascular system (1) and bone mass (12), as well as impairing exercise performance (16,32). The mechanistic bases of the maladaptations induced by clenbuterol in skeletal muscle remain largely unknown.Chronic administration of clenbuterol induces the transition from slow to fast muscle fiber types (35,49,53,56) a...

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“…Recent evidence indicates that RIP140 is a multi-functional coregulator important in regulating gene expression in metabolic tissues, specifically adipose tissue, muscle and liver [160][161][162]. Loss of RIP140 resulted in a lean phenotype, resistance to obesity and increased insulin sensitivity [160].…”

Section: Rip140mentioning

confidence: 99%

Transcriptional co-factors and hepatic energy metabolism

Sommerfeld

Krones-Herzig

Herzig

2011

Molecular and Cellular Endocrinology

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After binding to their cognate DNA-binding partner, transcriptional co-factors exert their function through the recruitment of enzymatic, chromatin-modifying activities. In turn, the assembly of co-factor-associated multi-protein complexes efficiently impacts target gene expression. Recent advances have established transcriptional co-factor complexes as a critical regulatory level in energy homeostasis and aberrant co-factor activity has been linked to the pathogenesis of severe metabolic disorders including obesity, type 2 diabetes and other components of the Metabolic Syndrome. The liver represents the key peripheral organ for the maintenance of systemic energy homeostasis, and aberrations in hepatic glucose and lipid metabolism have been causally linked to the manifestation of disorders associated with the Metabolic Syndrome. Therefore, this review focuses on the role of distinct classes of transcriptional co-factors in hepatic glucose and lipid homeostasis, emphasizing pathwayspecific functions of these co-factors under physiological and pathophysiological conditions.

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The metabolic coregulator RIP140: an update

Cited by 67 publications

References 37 publications

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis

Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle

Transcriptional co-factors and hepatic energy metabolism

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