Bone Marrow p16(INK4a)-Deficiency Does Not Modulate Obesity, Glucose Homeostasis or Atherosclerosis Development

Kristiaan Wouters*, Celine Cudejko, Marion J. J. Gijbels, Lucia Fuentes, Kadiombo Bantubungi, Jonathan Vanhoutte, Rebecca Dievart, Charlotte Paquet, Emmanuel Bouchaert, Sarah Anissa Hannou, Florence Gizard, Anne Tailleux, Menno P. J. de Winther, Bart Staels, Rejane Paumelle

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

Objective: A genomic region near the CDKN2A locus, encoding p16(INK4a), has been associated to type 2 diabetes and atherosclerotic vascular disease, conditions in which inflammation plays an important role. Recently, we found that deficiency of p16(INK4a) results in decreased inflammatory signaling in murine macrophages and that p16(INK4a) influences the phenotype of human adipose tissue macrophages. Therefore, we investigated the influence of immune cell p16(INK4a) on glucose tolerance and atherosclerosis in mice. Methods and Results: Bone marrow p16(INK4a)-deficiency in C57Bl6 mice did not influence high fat diet-induced obesity nor plasma glucose and lipid levels. Glucose tolerance tests showed no alterations in high fat diet-induced glucose intolerance. While bone marrow p16(INK4a)-deficiency did not affect the gene expression profile of adipose tissue, hepatic expression of the alternative markers Chi3l3, Mgl2 and IL10 was increased and the induction of pro-inflammatory Nos2 was restrained on the high fat diet. Bone marrow p16(INK4a)-deficiency in low density lipoprotein receptor-deficient mice did not affect western diet-induced atherosclerotic plaque size or morphology. In line, plasma lipid levels remained unaffected and p16w(INK4a)-deficient macrophages displayed equal cholesterol uptake and efflux compared to wild type macrophages. Conclusion: Bone marrow p16(INK4a)-deficiency does not affect plasma lipids, obesity, glucose tolerance or atherosclerosis in mice.
Original languageEnglish
Pages (from-to)e32440
JournalPLOS ONE
Volume7
Issue number3
DOIs
Publication statusPublished - 5 Mar 2012

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