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- Title
Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral Inflammation.
- Authors
André, Caroline; Guzman-Quevedo, Omar; Rey, Charlotte; Rémus-Borel, Julie; Clark, Samantha; Castellanos-Jankiewicz, Ashley; Ladeveze, Elodie; Leste-Lasserre, Thierry; Nadjar, Agnes; Abrous, Djoher Nora; Laye, Sophie; Cota, Daniela
- 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.
- Subjects
MICROGLIA; CELL proliferation; OBESITY; LEPTIN; CYTOKINES; WEIGHT gain; ADIPOSE tissues; ANIMAL experimentation; ANTINEOPLASTIC agents; BODY weight; HUMAN body composition; CELL physiology; CELLS; DIET; HYPOTHALAMUS; INFLAMMATION; INGESTION; INTERLEUKIN-1; MACROPHAGES; MICE; NUCLEOSIDES; TUMOR necrosis factors; DNA-binding proteins; CYTARABINE; PHARMACODYNAMICS
- Publication
Diabetes, 2017, Vol 66, Issue 4, p908
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0586