title: Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral Inflammation.
abstract: Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. We tested whether the intertwining of these two processes plays a role in the metabolic changes caused by 3 weeks of a high-saturated fat diet (HFD) consumption. Compared with chow-fed mice, HFD-fed mice had a rapid increase in body weight and fat mass and specifically showed an increased number of microglia in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet because feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation. Blocking HFD-induced cell proliferation by central delivery of the antimitotic drug arabinofuranosyl cytidine (AraC) blunted food intake, body weight gain, and adiposity. AraC treatment completely prevented the increase in number of activated microglia in the ARC, the expression of the proinflammatory cytokine tumor necrosis factor-α in microglia, and the recruitment of the nuclear factor-κB pathway while restoring hypothalamic leptin sensitivity. Central blockade of cell proliferation also normalized circulating levels of the cytokines leptin and interleukin 1β and decreased peritoneal proinflammatory CD86 immunoreactive macrophage number. These findings suggest that inhibition of diet-dependent microglia expansion hinders body weight gain while preventing central and peripheral inflammatory responses due to caloric overload.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: André
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|Facultad de Químico-Farmacobiología, Universidad Michoacána de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico.
authors.forename: Omar
authors.initials: O
authors.lastname: Guzman-Quevedo
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rey
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Rémus-Borel
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Samantha
authors.initials: S
authors.lastname: Clark
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Ashley
authors.initials: A
authors.lastname: Castellanos-Jankiewicz
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ladeveze
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Leste-Lasserre
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Nadjar
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France daniela.cota@inserm.fr nora.abrous@inserm.fr.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Djoher Nora
authors.initials: DN
authors.lastname: Abrous
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.|University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laye
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France daniela.cota@inserm.fr nora.abrous@inserm.fr.|University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Bordeaux, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cota
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000276:immunology; D000818:Animals; D050256:Antimitotic Agents / Q000494:pharmacology; D001087:Arabinonucleosides / Q000494:pharmacology; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000276:immunology*; D001835:Body Weight / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D003561:Cytarabine / Q000494:pharmacology; D003562:Cytidine / Q000494:pharmacology; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects / Q000276:immunology*; D007031:Hypothalamus / Q000187:drug effects / Q000276:immunology; D007249:Inflammation; D053583:Interleukin-1beta / Q000187:drug effects / Q000276:immunology; D020738:Leptin / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology; D009765:Obesity / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology; D015430:Weight Gain / Q000187:drug effects / Q000276:immunology*
chemical_list: D050256:Antimitotic Agents; D001087:Arabinonucleosides; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D020738:Leptin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003561:Cytarabine; D003562:Cytidine