VMHCIRCUITS · Deciphering central role of VMH circuits in regulating energy balance
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-04-01 → 2017-03-31
- EU contribution
- €145,846
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Deciphering central role of VMH circuits in regulating energy balance
Appetite and feeding behavior is tightly regulated by brain circuits which closely monitor peripheral energy stores and initiate appropriate behavioral responses to procure food. While much have learned about the organization of the neuronal networks that regulate appetite, role of an important brain structure, ventromedial hypothalamus (VMH) in feeding behavior remained elusive. In this project we used state of the art neuronal circuit dissection tools to decipher functional role of VMH in food intake regulation. Obesity remains a leading public health problem due to its association with cardiovascular disease, diabetes, cancer and other comorbidities. It is suggested that chronic imbalances in food intake and energy consumption contribute to excess weight gain. Therefore there is an urgent need to understand the basic brain organization that drives food intake and regulate energy homeostasis to uncover novel pharmacological targets for treatment of obesity and other feeding disorders. VMH region has long been implicated in energy homeostasis and appetite but some of the earlier observation had been controversial and direct evidence for the involvement of this region in feeding have been lacking. We aimed to decipher direct involvement of VMH in appetite regulation. In this project, we aimed to elucidate role of VMH region in appetite regulation and body weight. Our goal was to use state of the art cell type specific neuronal activity manipulation tools to selectively engage VMH neurons and investigate the relationship between their activity and food intake. Our results concluded that VMH activity has a permissive role in suppressing appetite, i.e. inhibition of VMH neurons is necessary but not sufficient to engage food intake.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- ISTANBUL MEDIPOL UNIVERSITESI · IstanbulCoordinatorTürkiye
Links
- View on CORDIS
- DOI: 10.3030/660981
- http://web.archive.org/web/20170422113003/http://denizatasoylab.com/
Data: CORDIS, © European Union