Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

6533b854fe1ef96bd12adfda

RESEARCH PRODUCT

Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

Christophe Guissard Cecile Hryhorczuk Caroline Rigault André Colom Emmanuelle Nédélec Luc Pénicaud Anne Lorsignol Claude Knauf Philippe Valet Alexandra Gouazé Xavier Fioramonti Alexandre Benani Rita Gerardy-schahn Alice Krezymon Thibaut Duparc Aleth Lemoine Xavier Brenachot Jean Gascuel

subject

Male MESH: Signal Transduction Pro-Opiomelanocortin [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition SYNAPTIC INPUT ORGANIZATION MESH: Energy Intake Weight Gain MESH: Mice Knockout Mice 0302 clinical medicine MESH : Sialic Acids NPY/AGRP NEURONS MESH: Pro-Opiomelanocortin MESH: Animals MESH : Neuronal Plasticity MESH: Neuronal Plasticity PLASTICITY MESH : Pro-Opiomelanocortin MESH : Adaptation Physiological Mice Knockout FEEDING CIRCUITS MESH : Organ Culture Techniques INSULIN-RESISTANCE 0303 health sciences Neuronal Plasticity POLYSIALIC ACID General Neuroscience Leptin MESH: Energy Metabolism digestive oral and skin physiology INDUCED OBESITY MESH : Sialyltransferases MESH : Weight Gain Articles Adaptation Physiological MESH : Mice Transgenic BODY-WEIGHT MESH: Dietary Fats Hypothalamus CELL-ADHESION MOLECULE MESH: Weight Gain Ghrelin ENERGY-BALANCE Melanocortin hormones hormone substitutes and hormone antagonists Signal Transduction medicine.medical_specialty MESH: Mice Transgenic MESH : Male MESH: Sialyltransferases MESH: Arcuate Nucleus Mice Transgenic MESH : Mice Inbred C57BL Biology MESH : Arcuate Nucleus MESH: Sialic Acids 03 medical and health sciences Organ Culture Techniques Insulin resistance MESH: Mice Inbred C57BL Arcuate nucleus Internal medicine MESH : Mice medicine Animals MESH: Mice 030304 developmental biology MESH : Signal Transduction Arcuate Nucleus of Hypothalamus MESH : Energy Intake medicine.disease Dietary Fats MESH: Adaptation Physiological Sialyltransferases MESH: Organ Culture Techniques MESH: Male Mice Inbred C57BL MESH : Energy Metabolism Endocrinology MESH: Nerve Net Sialic Acids MESH : Nerve Net MESH : Mice Knockout MESH : Animals Nerve Net Energy Intake Energy Metabolism [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition MESH : Dietary Fats 030217 neurology & neurosurgery Homeostasis Hormone

description

International audience; Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticity-driven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.

year	journal	country	edition	language
2012-08-29	The Journal of Neuroscience

https://doi.org/10.1523/jneurosci.0624-12.2012