Obesity is a disease of brain pathways regulating appetite and metabolism. Our aim is to help characterise these pathways to eventually develop safe and efficient therapies promoting satiety and weight loss.
PhD/MPhil projects available within the Blouet team
Techniques we use
We employ a multi-disciplinary approach to identify and characterise metabolic- and nutrient-sensing cells in the brain, perform discrete molecular manipulations of these cells, and decipher the downstream behavioural, metabolic and neuroendocrine circuits.
- We use molecular genetics and neurosurgery in model organisms to label molecularly- or activity-defined brain cell populations that are engaged during specific nutritional or metabolic contexts.
- We map the connectivity of these populations using viral neurotracing approaches.
- We determine how these cells and circuits are working in normal physiology and impaired in obesity and metabolic diseases.
- We characterise their functions using neuroanatomical and cell-specific inducible and reversible gain- and loss-of-function models (knock-out, DREADDs, neuronal silencing, etc). These models are combined with refined neuroendocrine, behavioural and metabolic assessments in behaving animals.
- We identify druggable targets to manipulate these cells and circuits in obese animals and test the efficiency of these approaches to treat obesity and metabolic diseases.
Congratulations to Sophie Buller who successfully defended her thesis recently, leading to the award of her PhD and she is now a postdoctoral research associate within the group.
Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence. Kohnke S, Buller S, Nuzzaci D, Ridley K, Lam B, Pivonkova H, Bentsen MA, Alonge KM, Zhao C, Tadross J, Holmqvist S, Shimizo T, Hathaway H, Li H, Macklin W, Schwartz MW, Richardson WD, Yeo GSH, Franklin RJM, Karadottir RT, Rowitch DH, Blouet C. Cell Reports, 2021
Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding. W Cheng, I Gonzalez, W Pan, AH Tsang, J Adams, E Ndoka, D Gordian, B Khoury, K Roelofs, S Evers, A MacKinnon, S Wu, H Frikke-Schmidt, JN Flak, JL Trevaskis,CJ Rhodes, S Fukada, RJ Seeley, DA Sandoval, DP Olson, C Blouet, MG MyersJr. Cell Metab. 2020 Jan.
Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons. Tsang AH, Nuzzaci D, Darwish T, Samudrala H, Blouet C.Mol Metab. 2020
Behavioural and neurochemical mechanisms underpinning the feeding-suppressive effect of GLP-1/CCK combinatorial therapy. Roth E, Benoit S, Quentin B, Lam B, Will S, Ma M, Heeley N, Darwish T, Shrestha Y, Gribble F, Reimann F, Pshenichnaya I, Yeo G, Baker DJ, Trevaskis JL, Blouet C.Mol Metab. 2021
Our highlight publication
Recently, we have shown that neurons of the nucleus of the solitari tract (NTS) expressing Calcitonin Receptor (CalR) and Prolactin Releasing Hormone (Prlrh) sense the amino acid Leucine, a signal for body’s protein availability. We found that these leucine-sensing neurons have unique properties, making them excellent candidates for appetite-suppressive drugs.
First, unlike many of appetite-regulating neurons in the NTS, activation of CalR/Prlrh neurons do not produce aversion (Cheng W, Cell Metabolism, 2020). This is important because nausea is one of the most common side-effect of current anti-obesity drugs.
Second, they project to and inhibit Agrp neurons in the hypothalamus, thus directly reducing hunger (Tsang A, Molecular metabolism, 2020), leading to negative energy balance.
Circulating metabolic hormones access the brain via the circumventricular organs, including the median eminence and the area postrema (© Blouet Lab).