Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes.
Yasmina KahoulFrédérik OgerJessica MontaignePhilippe FroguelChristophe BretonJean-Sébastien AnnicottePublished in: Biomolecules (2020)
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 p16INK4a-CDK4-E2F1/pRB and p19ARF-P53 (p14ARF 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.
Keyphrases
- insulin resistance
- adipose tissue
- type diabetes
- cell cycle
- high fat diet induced
- high fat diet
- metabolic syndrome
- genome wide association study
- skeletal muscle
- glycemic control
- weight loss
- cell proliferation
- genome wide association
- weight gain
- oxidative stress
- systematic review
- cardiovascular disease
- transcription factor
- fatty acid
- case control
- signaling pathway
- single cell
- mesenchymal stem cells
- risk factors