title: Bone marrow p16INK4a-deficiency does not modulate obesity, glucose homeostasis or atherosclerosis development.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Bone marrow p16(INK4a)-deficiency does not affect plasma lipids, obesity, glucose tolerance or atherosclerosis in mice.
authors.affiliation: Univ Lille Nord de France, Lille, France.
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Wouters
authors.forename: Céline
authors.initials: C
authors.lastname: Cudejko
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Lucia
authors.initials: L
authors.lastname: Fuentes
authors.forename: Kadiombo
authors.initials: K
authors.lastname: Bantubungi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vanhoutte
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dièvart
authors.forename: Charlotte
authors.initials: C
authors.lastname: Paquet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bouchaert
authors.forename: Sarah Anissa
authors.initials: SA
authors.lastname: Hannou
authors.forename: Florence
authors.initials: F
authors.lastname: Gizard
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Réjane
authors.initials: R
authors.lastname: Paumelle
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D001853:Bone Marrow / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency*; D059305:Diet, High-Fat / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D011973:Receptors, LDL; D005947:Glucose