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Plasticity of feeding circuits


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Researchers

A. Lemoine.

Enginneers and technicians

F. Liénard, E. Nedelec.

PhD students

S. Ben Fradj.

Trainees

L. Guenot.

The melanocortin system is one of the most important neuronal pathways involved in the regulation of energy balance and is probably the best characterized. Orexigenic Agouti-related peptide (AgRP)- and anorexigenic proopiomelanocortin (POMC)-expressing neurons are key elements of this system. These neurons are sensitive to circulating molecules and receive many excitatory and inhibitory inputs from various brain areas. According to sensory and metabolic information they integrate, these neurons control different aspects of feeding behavior. Interestingly, composition and abundance of pre-synaptic inputs onto AgRP and POMC neurons can vary in the adult hypothalamus of mice in response to changes in the metabolic state. Lack of plasticity in this circuit might confer risk for obesity.

Key words : Neuroendocrinology, Hypothalamus, Synaptic plasticity, Melanocortin system, Food intake, Obesity research, Obesity predisposition, Epigenetics.

Thematic : Coupling molecular analysis, brain histology, pharmacology and gene manipulation in experimental murine models to investigate the neurobiological bases of feeding behavior and to identify molecules involved in energy homeostasis.

Research group in detail Open all the tabs

Little is known about the plasticity of brain feeding circuits and its exact role in the maintenance of energy homeostasis, except that the synaptic plasticity in response to changes in the metabolic state is coordinated by hormonal signals and that altered connectivity is found in obese mice.

    Sub-topics:
  • - What is the exact role of plasticity-related processes in eating behavior?
  • - Does inadequacy for rewiring feeding circuits underlies the obese phenotype or develops along with metabolic imbalance?
  • - What are the regulatory mechanisms driving the rewiring of feeding circuits during overfeeding?
  • - Can stimulation of plasticity be considered as a strategy for accelerating body weight loss and improving metabolic performance in the management of obesity?

Responses to dietary interventions are examined at the molecular and neuroanatomical levels while metabolic consequences are measured through behavioral and physiological studies. We monitor food intake in real-time to study meal structure. We perform extractions from micro-dissected biopsies and in vivo chromatin-immunoprecipitation (ChIP) for epigenetic and gene expression studies. We develop electron microscopy and 3D confocal imaging to assess morphological plasticity. We manipulate brain molecular targets to link molecular and histological correlates to behavior. We use stereotactic surgery, pharmacology, viral vectors, cre-lox system and transgenic mice to reach spatial, temporal, or cell-specific resolution.

Rodent

We have expertise in dietary manipulation and metabolic assessment in mice. We perform targeted (or not) gene manipulation, neuroanatomical studies and cell-specific (or not) molecular studies.

Modèle

Project ANR NCAM2 : « Neural control of appetite and metabolism by neural cell adhesion molecule » (ANR- 13-JSV1-0003-01).

Research award from the Institut Benjamin Delessert

Research award from the Société de Nutrition

« Bonus Qualité Recherche » Université de Bourgogne-Franche Comté

Incitative funds from INRA « métaprogramme SweetLipKid »

Nuzzaci D, Laderrière A, Lemoine A, Nédélec E, Pénicaud L, Rigault C and Benani A. Plasticity of the melanocortin system: determinants and possible consequences on food intake. Front. Endocrinol. 2015, 6:143.

Brenachot X, Rigault C, Nédélec E, Laderrière A, Khanam T, Gouazé A, Chaudy S, Lemoine A, Datiche F, Gascuel J, Pénicaud L, Benani A. The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice. Mol Metab. 2014 Jun 13;3(6):619-29.

Maurin AC, Benani A, Lorsignol A, Brenachot X, Parry L, Carraro V, Guissard C, Averous J, Jousse C, Bruhat A, Chaveroux C, B'chir W, Muranishi Y, Ron D, Pénicaud L, Fafournoux P. Hypothalamic eIF2a signaling regulates food intake. Cell Rep. 2014 Feb 13;6(3):438-44.

Drougard A, Duparc T, Brenachot X, Carneiro L, Gouazé A, Fournel A, Geurts L, Cadoudal T, Prats AC, Pénicaud L, Vieau D, Lesage J, Leloup C, Benani A, Cani PD, Valet P, Knauf C. Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose metabolism in the onset of diabetes. Antioxid Redox Signal. 2014 Feb 1;20(4):557-73.

Gouazé A, Brenachot X, Rigault C, Krezymon A, Rauch C, Nédélec E, Lemoine A, Gascuel J, Bauer S, Pénicaud L, Benani A. Cerebral cell renewal in adult mice controls the onset of obesity. PLoS One. 2013 Aug 13;8(8):e72029.

Matarazzo V, Schaller F, Nédélec E, Benani A, Pénicaud L, Muscatelli F, Moyse E, Bauer S. Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. J Neurosci. 2012 Nov 28;32(48):17097-107.

Benani A, Hryhorczuk C, Gouazé A, Fioramonti X, Brenachot X, Guissard C, Krezymon A, Duparc T, Colom A, Nédélec E, Rigault C, Lemoine A, Gascuel J, Gerardy-Schahn R, Valet P, Knauf C, Lorsignol A, Pénicaud L. Food intake adaptation to dietary fat involves PSA-dependent rewiring of the arcuate melanocortin system in mice. J Neurosci. 2012 Aug 29;32(35):11970-9.

Attané C, et al. Apelin treatment increases complete Fatty Acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice. Diabetes. 2012 Feb;61(2):310-20.

  • Région Bourgogne
  • FEDER
  • ANR
  • Société Française de Nutrition
  • Institut Benjamin Delessert