Nutrient sensing in the brain
Lead Research Organisation:
University of Cambridge
Department Name: UNLISTED
Abstract
The aim of this research is to better understand the brain pathways regulating appetite, to design better drugs that would decrease hunger and help treat obesity. We focus on brain pathways sensing protein, because proteins are really efficient at suppressing hunger. We are identifying and characterising specialized cells in the brain that can tell how much protein we’ve eaten and in response to that, make us fell hungrier or more sated.
Technical Summary
Growing evidence indicates that human obesity is a disease of brain pathways regulating appetite. The characterization of these pathways to eventually develop safe and efficient therapies mitigating hyperphagia is one of the top priorities in obesity research. Although protein is known to be the most potent appetite suppressant among all macronutrients, little is known about how the mammalian brain senses protein availability to create neural representations that guide behaviour and modulate metabolism. The goal of this programme is to characterise the central representation of protein abundance and determine whether brain protein sensing pathways can be targeted to produce satiety and improve energy balance.
We hypothesise that the branched-chain amino acid leucine signals protein abundance to brain circuits controlling appetite and metabolism. During the past 5-yrs, we have characterised hypothalamic leucine-sensing neurons and are developing strategies to specifically target these neurons using molecular genetics. We are developing gain- and loss-of-function approaches to test the role of discrete leucine-sensing neuronal populations in the control of appetite and energy balance in mice. Using these models, we are testing the role of specific neuronal populations in leucine and protein sensing, in the regulation of energy balance and in the response to diets with varying protein contents. We are planning to characterise the neural circuits downstream from leucine sensing neurons , and determine how these circuits are intergrated with energy sensing neural circuits controlling appetite and weight.
We hypothesise that the branched-chain amino acid leucine signals protein abundance to brain circuits controlling appetite and metabolism. During the past 5-yrs, we have characterised hypothalamic leucine-sensing neurons and are developing strategies to specifically target these neurons using molecular genetics. We are developing gain- and loss-of-function approaches to test the role of discrete leucine-sensing neuronal populations in the control of appetite and energy balance in mice. Using these models, we are testing the role of specific neuronal populations in leucine and protein sensing, in the regulation of energy balance and in the response to diets with varying protein contents. We are planning to characterise the neural circuits downstream from leucine sensing neurons , and determine how these circuits are intergrated with energy sensing neural circuits controlling appetite and weight.
People |
ORCID iD |
Clemence Blouet (Principal Investigator) |
Publications
Tsang A
(2020)
Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons
in Molecular Metabolism
Tsang A
(2023)
A pipeline for identification and validation of brain targets for weight loss.
in Nature reviews. Endocrinology
Roth E
(2021)
Behavioural and neurochemical mechanisms underpinning the feeding-suppressive effect of GLP-1/CCK combinatorial therapy.
in Molecular metabolism
Romero-Picó A
(2018)
Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake.
in Neuropharmacology
Hornigold D
(2018)
A GLP-1:CCK fusion peptide harnesses the synergistic effects on metabolism of CCK-1 and GLP-1 receptor agonism in mice
in Appetite
Cheng W
(2020)
Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.
in Cell metabolism
Buller S
(2023)
Median eminence myelin continuously turns over in adult mice.
in Molecular metabolism
Buller S
(2023)
Median eminence myelin continuously turns over in adult mice.
Buller S
(2023)
Median eminence myelin continuously turns over in adult mice.
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00014/1 | 01/04/2018 | 31/03/2024 | £2,995,583 | ||
MC_UU_00014/2 | Transfer | MC_UU_00014/1 | 01/04/2018 | 31/03/2024 | £2,871,979 |
MC_UU_00014/3 | Transfer | MC_UU_00014/2 | 01/04/2018 | 31/03/2024 | £1,667,444 |
MC_UU_00014/4 | Transfer | MC_UU_00014/3 | 01/04/2018 | 31/03/2024 | £1,743,788 |
MC_UU_00014/5 | Transfer | MC_UU_00014/4 | 01/04/2018 | 31/03/2024 | £3,355,490 |
MC_UU_00014/6 | Transfer | MC_UU_00014/5 | 01/04/2018 | 31/03/2024 | £1,325,715 |
Description | Enabling technologies |
Amount | £1,000,000 (GBP) |
Funding ID | MC_UU_00014/5 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2018 |
End | 03/2024 |
Description | Programme Leader Track position at the MRC Metabolic Disease Unit |
Amount | £16,560,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2018 |
End | 04/2023 |
Description | John Apergis-Schoute, University of Leicester |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provide a new research model to our collaborator |
Collaborator Contribution | The collaborator performs experiments for us. |
Impact | Research data |
Start Year | 2019 |
Description | Martin Myers |
Organisation | University of Michigan |
Country | United States |
Sector | Academic/University |
PI Contribution | Research models |
Collaborator Contribution | Research animals |
Impact | 1 publication in Cell Metabolism |
Start Year | 2019 |
Description | cacna1g KO tissues |
Organisation | University of Southern Denmark |
Country | Denmark |
Sector | Academic/University |
PI Contribution | analysis |
Collaborator Contribution | samples |
Impact | data |
Start Year | 2018 |