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?
Heeley N, Kirwan P, Darwish T, Arnaud M, Evans ML, Merkle FT, Reimann F, Gribble FM, Blouet C. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights. Mol Metab. 2018 Feb 7. DOI:10.1016/j.molmet.2018.01.021. PMID: 29439854.
Burke LK, Darwish T, Cavanaugh AR, Virtue S, Roth E, Morro J, Liu SM, Xia J, Dalley JW, Burling K, Chua S, Vidal-Puig T, Schwartz GJ, Blouet C. mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice. Elife. 2017 May 23;6. DOI:10.7554/eLife.22848. PMID:28532548 PMCID:PMC5441868.
Cavanaugh AR, Schwartz GJ, Blouet C. High-fat feeding impairs nutrient sensing and gut brain integration in the caudomedial nucleus of the solitary tract in mice. PLoS One. 2015 Mar 16;10(3):e0118888. doi: 10.1371/journal.pone.0118888. PMID: 25774780. PMCID: PMC4361711
Blouet C, Jo YW, Li X, Schwartz GJ. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neuroscience, 29(26):8302-11. 2009. PMID: 19571121. PMCID: PMC2740923.