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

• Main Authors: Yasmina Kahoul, Frédérik Oger, Jessica Montaigne, Philippe Froguel, Christophe Breton, Jean-Sébastien Annicotte
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Biomolecules
• Subjects: adipogenesis; insulin sensitivity; inflammation; obesity; oxidative activity; senescence
• Online Access: https://www.mdpi.com/2218-273X/10/9/1350

Besides its role as a cell cycle and proliferation regulator, the <i>INK4a/ARF</i> (<i>CDKN2A</i>) 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 <i>INK4a/ARF</i> locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis.