Human obesity is predominantly a disease of brain pathways regulating appetite. Our aim is to help characterize these pathways to eventually develop safe and efficient therapies promoting satiety.
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. Data obtained across taxa from flies to humans indicate that evolutionary-conserved homeostatic mechanisms tightly control protein intake, and that this control is prioritized over the control of carbohydrate, fat or energy intake. Targeting protein-sensing mechanisms could therefore represent a novel avenue for the development of anti-obesity drugs.
The Blouet Lab employs a multi-disciplinary approach coupling calcium imaging to characterize the neurophysiology of metabolic-sensing neurons, discrete manipulations of brain neurocircuits and nutrient sensing pathways using cutting-edge molecular genetics, and refined functional assessments in behaving rodents to characterize how proteins are detected by the brain to maintain energy homeostasis in health and disease.
Our current research focuses on the following questions:
Can we target hypothalamic protein-sensing cells to produce satiety and improve energy balance?
What is the neuronal representation of central protein abundance?
Are protein-sensing circuits integrated with neurocircuits sensing gut-derived and adiposity signals? Can we target the integration mechanisms to maximise beneficial outcomes on appetite and weight control?
Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons. Anthony H Tsang , Danae Nuzzaci, Tamana Darwish, Havish Samudrala, Clémence Blouet. Mol Metab 2020 PMID: 32898712 PMCID: PMC7549147
Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding. Cheng W, Gonzalez I, Pan W, Tsang AH, Adams J, Ndoka E, Gordian D, Khoury B, Roelofs K, Evers SS, MacKinnon A, Wu S, Frikke-Schmidt H, Flak JN, Trevaskis JL, Rhodes CJ, Fukada SI, Seeley RJ, Sandoval DA, Olson DP, Blouet C, Myers MG Jr. Cell Metab. 2020 PMID: 31955990 PMCID: PMC7104375
Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake.Adriaenssens AE, Biggs EK, Darwish T, Tadross J, Sukthankar T, Girish M, Polex-Wolf J, Lam BY, Zvetkova I, Pan W, Chiarugi D, Yeo GSH, Blouet C, Gribble FM, Reimann F. Cell Metab. 2019 PMID: 31447324 PMCID: PMC6838660
Mapping neuronal inputs to Kiss1 neurons in the arcuate nucleus of the mouse.Yeo SH, Kyle V, Blouet C, Jones S, Colledge WH. PLoS One. 2019 PMID: 30917148 PMCID: PMC6436706
Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights. Nicholas Heeley, Peter Kirwan, Tamana Darwish, Marion Arnaud, Mark L Evans, Florian T Merkle, Frank Reimann, Fiona M Gribble, Clemence Blouet . Mol Metab. 2018 PMID: 29439854 PMCID: PMC5985239
mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice. Luke K Burke, Tamana Darwish, Althea R Cavanaugh , Sam Virtue , Emma Roth , Joanna Morro , Shun-Mei Liu , Jing Xia, Jeffrey W Dalley , Keith Burling , Streamson Chua, Toni Vidal-Puig , Gary J Schwartz , Clémence Blouet. eLife, 2017 PMID: 28532548 PMCID: PMC5441868