Bone Marrow P16INK4a-deficiency Does Not Modulate Obesity, Glucose Homeostasis or Atherosclerosis Development

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Mar 10

PMID 22403661

Citations 9

Authors

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

Affiliations

Soon will be listed here.

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 p16(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.

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