Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral Inflammation.
Diabetes. 2016-11-30; 66(4): 908-919
DOI: 10.2337/db16-0586
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1. Diabetes. 2017 Apr;66(4):908-919. doi: 10.2337/db16-0586. Epub 2016 Nov 30.
Inhibiting Microglia Expansion Prevents Diet-Induced Hypothalamic and Peripheral
Inflammation.
André C(1)(2), Guzman-Quevedo O(1)(2)(3), Rey C(4)(5), Rémus-Borel J(4)(5), Clark
S(1)(2), Castellanos-Jankiewicz A(1)(2), Ladeveze E(1)(2), Leste-Lasserre
T(1)(2), Nadjar A(4)(5), Abrous DN(6)(2), Laye S(4)(5), Cota D(6)(2).
Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U1215, Bordeaux, France.
(2)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, U1215, Bordeaux, France.
(3)Facultad de Químico-Farmacobiología, Universidad Michoacána de San Nicolás de
Hidalgo, Morelia, Michoacán, Mexico.
(4)INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
(5)University of Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286,
Bordeaux, France.
(6)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U1215, Bordeaux, France .
Comment in
Diabetes. 2017 Apr;66(4):804-805.
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.
© 2017 by the American Diabetes Association.
DOI: 10.2337/db16-0586
PMID: 27903745 [Indexed for MEDLINE]