Project description
Gut-brain communication and obesity
Neural gut-brain communication helps to monitor gastrointestinal organs and contributes to energy and glucose homeostasis regulation. Its disruption develops in obesity and correlates with overeating and insulin resistance. This EU-funded project will employ a combination of modern molecular neuroscience tools and mouse genetic approaches to determine the identity of gut-innervating neurons, define their role in feeding behaviour and glucose metabolism, and map the neurocircuitry to downstream brain sites. Successful outcome of the project will help to overcome challenges associated with targeting distinct neurons in a cell-type and organ-specific manner, an important first step to developing new therapies to treat obesity.
Objective
Communication between the gut and the brain is essential for metabolic function. Sensory afferent neurons are key gut-brain connectors that monitor gastrointestinal (GI) tract organs, including the stomach, the duodenum, the liver, and the portal vein area, and thereby critically contribute to systemic energy and glucose homeostasis regulation. Disruption of this neural gut-brain communication develops in obesity and correlates with overeating, body weight gain, and insulin resistance. However, the relevant sensory neuronal populations innervating the GI tract organs along with the pertaining underlying metabolic neurocircuitry still remain to be elucidated. To date, advances in this field have been impeded by the challenges associated with targeting distinct sensory neurons of vagal and spinal origin in a cell-type and organ-specific manner, thereby making the accurate determination of their metabolic function highly difficult. Thus, the proposed comprehensive research program will employ a combinatorial set of modern molecular systems neuroscience tools and novel mouse genetic approaches to (1) elucidate the role of specific sensory neurons in feeding behavior and glucose metabolism, (2) determine the functional metabolic neurocircuitry of GI tract-innervating vagal and spinal afferents in an organ-specific manner, (3) study the effects of obesity on their transcriptomes, and (4) map their functional connectivity as well as synaptic adaptions to downstream brain sites. Collectively, the overarching goals of these four autonomous but complementary projects are to gain greater insights into the integral components of sensory neurons as gut-brain connectors in controlling metabolism as a first step to developing new therapies to treat obesity.
Fields of science
Programme(s)
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Funding Scheme
ERC-STG - Starting GrantHost institution
80539 Munchen
Germany