Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes

Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphis...

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Autores principales: Kahoul, Yasmina, Oger, Frédérik, Montaigne, Jessica, Froguel, Philippe, Breton, Christophe, Annicotte, Jean-Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563355/
https://www.ncbi.nlm.nih.gov/pubmed/32971832
http://dx.doi.org/10.3390/biom10091350
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author Kahoul, Yasmina
Oger, Frédérik
Montaigne, Jessica
Froguel, Philippe
Breton, Christophe
Annicotte, Jean-Sébastien
author_facet Kahoul, Yasmina
Oger, Frédérik
Montaigne, Jessica
Froguel, Philippe
Breton, Christophe
Annicotte, Jean-Sébastien
author_sort Kahoul, Yasmina
collection PubMed
description Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphisms in this locus are risk factors for obesity and related metabolic diseases including cardiovascular complications and type-2 diabetes (T2D). Recent studies showed that both p16(INK4a)-CDK4-E2F1/pRB and p19(ARF)-P53 (p14(ARF) in humans) related pathways regulate adipose tissue (AT) physiology and adipocyte functions such as lipid storage, inflammation, oxidative activity, and cellular plasticity (browning). Targeting these metabolic pathways in AT emerged as a new putative therapy to alleviate the effects of obesity and prevent T2D. This review aims to provide an overview of the literature linking the INK4a/ARF locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis.
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spelling pubmed-75633552020-10-27 Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes Kahoul, Yasmina Oger, Frédérik Montaigne, Jessica Froguel, Philippe Breton, Christophe Annicotte, Jean-Sébastien Biomolecules Review Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphisms in this locus are risk factors for obesity and related metabolic diseases including cardiovascular complications and type-2 diabetes (T2D). Recent studies showed that both p16(INK4a)-CDK4-E2F1/pRB and p19(ARF)-P53 (p14(ARF) in humans) related pathways regulate adipose tissue (AT) physiology and adipocyte functions such as lipid storage, inflammation, oxidative activity, and cellular plasticity (browning). Targeting these metabolic pathways in AT emerged as a new putative therapy to alleviate the effects of obesity and prevent T2D. This review aims to provide an overview of the literature linking the INK4a/ARF locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis. MDPI 2020-09-22 /pmc/articles/PMC7563355/ /pubmed/32971832 http://dx.doi.org/10.3390/biom10091350 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kahoul, Yasmina
Oger, Frédérik
Montaigne, Jessica
Froguel, Philippe
Breton, Christophe
Annicotte, Jean-Sébastien
Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title_full Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title_fullStr Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title_full_unstemmed Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title_short Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes
title_sort emerging roles for the ink4a/arf (cdkn2a) locus in adipose tissue: implications for obesity and type 2 diabetes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563355/
https://www.ncbi.nlm.nih.gov/pubmed/32971832
http://dx.doi.org/10.3390/biom10091350
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