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Deciphering central role of VMH circuits in regulating energy balance

Objective

Incidence of obesity has been steadily increasing for the last few decades. A corresponding rise in the obesity associated co-morbidities such as cardiovascular diseases and type-2 diabetes makes it an acute priority to understand the mechanisms underlying body weight regulation. It is well established that distributed brain circuits tightly monitor and regulate energy stores. Of particular interest, electrical and pharmacological manipulations to ventromedial portion of the hypothalamus (VMH), results in dramatic alterations in food intake, adiposity and glucose homeostasis in animal models. Furthermore, human genetic screens have shown that, at least for a subset of morbidly obese patients, genes that are heavily expressed in VMH are altered. Collectively these observations point to a central role for VMH in driving negative energy balance, yet relatively little is known how VMH neurons achieve this. To identify novel mechanisms for controlling energy balance, we propose to determine the following: 1) identify signals that regulate VMH neuronal activity, this includes synaptic input as well as circulating signals, 2) dissect out immediate downstream and upstream synaptic targets of VMH neurons mediating food intake and glucose homeostasis. To achieve this, we will use state of the art neuronal circuit mapping techniques involving virus based retrograde tracers and optogenetics. By combining functional electrophysiology and morphological approaches we will determine brain regions that has connections to and from VMH and evaluate behavioral and physiological significance each of these connections in-vivo. Understanding the basics of the functional VMH-wiring diagram will help determine how these neuronal circuits change under the conditions of metabolic and feeding disorders and will provide basis of targeted approaches for treatment.

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MSCA-IF-EF-RI - RI – Reintegration panel

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(opens in new window) H2020-MSCA-IF-2014

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Coordinator

ISTANBUL MEDIPOL UNIVERSITESI
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 145 845,60
Address
ATATURK BULVARI 27 FAITH KASAPDEMIRHUN MAHALLESI
34083 Istanbul
Türkiye

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Region
İstanbul İstanbul İstanbul
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 145 845,60
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