High fat diet rapidly induces brain-plasticity-related transcriptomic signature in hypothalamus: role in energy homeostasis

International audienceWe have investigated the early events that are induced by a hypercaloric hyperlipidic diet in mice. The high fat diet rapidly induced metabolic imbalance, as soon as the first day, which is characterized by a large increase in energy intake and several others metabolic alterations such as hypercholesterolemia, and glucose intolerance. However, the diet-induced metabolic imbalance was fully reversed after a week, suggesting that a physiological adaptive response has been then induced, probably in order to counteract the deleterious excessive caloric intake in these normal mice. The hypothalamus, which ensures coordination of endocrine and autonomic functions, and thus long-term stability of the inner milieu, is of major importance in the control of food intake and energy homeostasis. Interestingly, the hypothalamus remains "plastic" in adulthood, meaning that neuronal networks in this structure can undergo functional or morphological remodeling aimed at integrating modifications in environmental conditions and in physiological states. We hypothesized that brain plasticity could occur in hypothalamus after the change in diet condition, to re-wire hypothalamic neuronal networks that control the eating behavior to correctly fit the food intake with the energy expenditure. By the use of a transcriptomic tool, we observed that high fat diet was associated with numerous up-regulation of mRNA, markers of brain plasticity as soon as the first day after the change in diet. This transcriptional modification suggests the initiation of one main feature of brain plasticity that is synaptogenesis. Interestingly, the kinetics of molecular signature anticipates the food behavior restoration, suggesting that a causal relation may exist