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Conférence mensuelle - Marc Claret / PhD seminar seriesQualitatively-different mitochondrial fusion in POMC neurons divergently regulates energy balance and glucose homeostasis

Abstract :

Marc Claret, head of the IDIBAPS Group Neuronal Control of Metabolism, has received a Consolidator Grant from the European Research Council (ERC) to study the populations of neurons that regulate the body’s energy status.

Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus are critical regulators of appetite, energy expenditure and glucose metabolism. POMC neurons are able to sense circulating hormones and nutrients informing about the energy status of the organism. However the molecular mechanisms underlying nutrient-sensing in POMC neurons remain incompletely understood. Mitochondria are key organelles implicated in cellular nutrient/energy management and are able to bioenergetically adjust to different metabolic situations. A remarkable feature of mitochondria is their capacity to change their morphology through coordinated fusion and fission events, a mechanism that links nutrient availability with bioenergetic adaptations. Mitochondrial fusion is a process that requires the GTPases mitofusin (Mfn) 1, Mfn2 and OPA1.

We hypothesized that mitochondrial fusion in hypothalamic POMC neurons may represent primary nutrient/energy-sensing processes implicated in the hypothalamic regulation of energy balance and metabolism. To test this hypothesis we have generated mice lacking the main fusogenic proteins specifically in POMC neurons and conducted detailed phenotyping and molecular studies. Our data demonstrate divergent metabolic outcomes depending on the deleted fusion protein, which are mediated by different tissues and molecular processes.
These results suggest that mitochondrial dynamics in POMC neurons is a critical mechanism implicated in the maintenance of systemic energy balance and glucose homeostasis.

Selected publications

Recent relevant publications

- Ramirez S et al. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control. Cell Metab 25(6):1390-1399 (2017).

- Schneeberger M et al. Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis. Cell Reports 12(3):361-70 (2015).

- Schneeberger M et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155(1):172-87 (2013).

Scientific focus :

Research conducted over the last 10 years has firmly established the mediobasal hypothalamus as a critical central nervous system area in the regulation of whole-body energy homeostasis and metabolism. Marc Claret’s general research interests are focused on the study of the molecular mechanisms by which particular hypothalamic neural networks control food intake, body weight and glucose metabolism. To achieve this aim, his group uses genetic approaches to manipulate defined populations of neurons in order to correlate the function of a particular protein with specific physiological and behavioral outputs. This approach is further complemented with a wide range of additional techniques from different disciplines, such as physiology, molecular biology, cellular biology and imaging amongst others. Understanding the physiological mechanisms controlling energy balance and the pathophysiological alterations leading to obesity and type-2 diabetes, are the first steps towards developing new and more effective therapeutic approaches for the treatment of these metabolic conditions.

PhD seminar series

La Fédération Bordeaux Neurocampus, en concertation avec l'Ecole Doctorale SVS, met en place une série de conférences destinée à l'ensemble des étudiants effectuant leur thèse dans les laboratoires de neurosciences de Bordeaux Neurocampus. Les doctorants Neuroscience in Bordeaux Association (NBA) sont chargés de l'organisation. 

Modalités : tous les premiers vendredi de chaque mois à 11h30 (durée : 1h), puis pizzas avec les étudiants et rencontres avec les personnes intéressées l'après-midi

If you are interested to share pizzas and a good moment with him (12h30 - 14h), please register on this Doodle : soon) (maximum 15 people, first-come-first-served!)

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