Cerebral cell renewal in adult mice controls the onset of obesity

• Published in: Plos One 8 (8), e72029. (2013)
• Main Authors: Gouazé, Alexandra, Brenachot, Xavier, Rigault, Caroline, Krezymon, Alice, Rauche, Camille, Nedelec, Emmanuelle, Lemoine, Aleth, Gascuel, Jean, Bauer, Sylvian, Pénicaud, Luc
• Format: Publication
• Language: English
• Published: 2013
• Subjects: Alimentation et Nutrition; Food and Nutrition; Neurons and Cognition; Neurosciences

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.