title: Cerebral cell renewal in adult mice controls the onset of obesity.
abstract: The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance.
authors: Centre des Sciences du Goût et de l'Alimentation, Centre National de la Recherche Scientifique - Institut National de la Recherche Agronomique - Université de Bourgogne, Dijon, France.
authors: Alexandra
authors: A
authors: Gouazé
authors: Xavier
authors: X
authors: Brenachot
authors: Caroline
authors: C
authors: Rigault
authors: Alice
authors: A
authors: Krezymon
authors: Camille
authors: C
authors: Rauch
authors: Emmanuelle
authors: E
authors: Nédélec
authors: Aleth
authors: A
authors: Lemoine
authors: Jean
authors: J
authors: Gascuel
authors: Sylvian
authors: S
authors: Bauer
authors: Luc
authors: L
authors: Pénicaud
authors: Alexandre
authors: A
authors: Benani
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D049109:Cell Proliferation; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000209:etiology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D015430:Weight Gain
chemical_list: D011333:Pro-Opiomelanocortin
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