The tumour suppressor CDKN2A/p16(INK4a) regulates adipogenesis and bone marrow-dependent development of perivascular adipose tissue

Kristiaan Wouters, Yann Deleye, Sarah A. Hannou, Jonathan Vanhoutte, Xavier Marechal, Augustin Coisne, Madjid Tagzirt, Bruno Derudas, Emmanuel Bouchaert, Christian Duhem, Emmanuelle Vallez, Casper G. Schalkwijk, Francois Pattou, David Montaigne, Bart Staels*, Rejane Paumelle

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)


The genomic CDKN2A/B locus, encoding p16(INK4a) among others, is linked to an increased risk for cardiovascular disease and type 2 diabetes. Obesity is a risk factor for both cardiovascular disease and type 2 diabetes. p16(INK4a) is a cell cycle regulator and tumour suppressor. Whether it plays a role in adipose tissue formation is unknown. p16(INK4a) knock-down in 3T3/L1 preadipocytes or p16(INK4a) deficiency in mouse embryonic fibroblasts enhanced adipogenesis, suggesting a role for p16(INK4a) in adipose tissue formation. p16(INK4a)-deficient mice developed more epicardial adipose tissue in response to the adipogenic peroxisome proliferator activated receptor gamma agonist rosiglitazone. Additionally, adipose tissue around the aorta from p16(INK4a)-deficient mice displayed enhanced rosiglitazone-induced gene expression of adipogenic markers and stem cell antigen, a marker of bone marrow-derived precursor cells. Mice transplanted with p16(INK4a)-deficient bone marrow had more epicardial adipose tissue compared to controls when fed a high-fat diet. In humans, p16(INK4a) gene expression was enriched in epicardial adipose tissue compared to other adipose tissue depots. Moreover, epicardial adipose tissue from obese humans displayed increased expression of stem cell antigen compared to lean controls, supporting a bone marrow origin of epicardial adipose tissue. These results show that p16(INK4a) modulates epicardial adipose tissue development, providing a potential mechanistic link between the genetic association of the CDKN2A/B locus and cardiovascular disease risk.

Original languageEnglish
Pages (from-to)516-524
Number of pages9
JournalDiabetes & Vascular Disease Research
Issue number6
Publication statusPublished - Nov 2017


  • p16(INK4a)
  • CDKN2A
  • adipogenesis
  • perivascular adipose tissue
  • bone marrow
  • CDK4

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