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Institute of Metabolic Science

Metabolic Research Laboratories
 

Research Interests:

My broad aim is to identify how the mammalian brain represents internal nutrient and energy availability and orchestrates behavioural, metabolic and endocrine responses for nutritional homeostasis.

Theme 1: Brain nutrient sensing for amino acid homeostasis:

Half of the amino acids cannot be synthesized by mammalian cells and must be obtained through the diet. A shortage of these essential amino acids rapidly drives protein hunger, yet high circulating levels of amino acids is toxic, leading to metabolic and neurological diseases.

We work under the hypothesis that homeostatic mechanisms regulate peripheral amino acid availability to maintain nutritional balance and ensure survival. Impairments in these pathways contribute to the pathophysiology of obesity and metabolic diseases, but little is known about how this is achieved.

Our goal is to understand how the mammalian brain senses peripheral amino acid availability and produces behavioural and metabolic responses that maintain amino acid homeostasis, and how this regulation is integrated with or might conflict with the maintenance of energy homeostasis. Eventually our goal is to determine if brain protein-sensing pathways represent effective targets for weight-loss interventions and restoring metabolic health.

Theme 2: Nutrient sensing in oligodendrocytes

Oligodendrocytes are myelin-forming cells that ensheathe axons to allow rapid saltatory conduction of action potentials. While oligodendrocytes are typically long-lived in a healthy brain, we have found that they rapidly turnover in the median eminence—the brain region through which hypothalamic neurons access blood signals—leading to rapid myelin renewal. This plasticity is regulated by nutritional and metabolic cues. We are actively working on identifying the functional significance of median eminence oligodendrocyte and myelin turnover in neuroendocrine functions and energy and glucose homeostasis.

Theme 3: Targeting brain nutrient sensing for weight loss 

Our third goal is to identify the mechanism of action of GLP-1 based weight-loss drugs.


Group Members:

Dr Thomas Brown, Research Associate - tb807 at medschl.cam.ac.uk 

Dr Anthony Tsang, Research Associate - at783 at medschl.cam.ac.uk 


Funding:

Medical Research Council 

Diabetes UK 

Publications

Key publications: 

Cav3.1 is a leucine sensor in POMC neurons mediating appetite suppression and weight loss. Anthony H. Tsang, Nicholas Heeley, Constanza Alcaino, Eunsang Hwang, Brian Y. Lam, Taufiq Rahman, Tamana Darwish, Danae Nuzzaci, Richard G. Kay, Amar Sarkar, Ruiyan Wang, Nihal Basha, Austin Punnoose, Peter Kirwan, Marcella Ma, Giles S. Yeo, Florian T. Merkle, Fiona M. Gribble, Frank Reimann, Kevin Williams, Clemence Blouet. Preprint. https://doi.org/10.1101/2024.09.13.612843

Adult oligodendrogenesis gates arcuate neuronal glucose sensing through remodelling of the blood-hypothalamus barrier via ADAMTS4. Sophie Buller, Emily Staricoff, Christine Riches, Anthony Tsang, Masa Josipovic, Kentaro Ikemura, Gabriel Opoku, Ikumi Sato, Satoshi Hirohata, Saskia Stenzel, Stuart Nayar, Marta Ramos Vega, Jacob Hecksher-Sorensen, Sebastian Timmler, Georgina Dowsett, Brian Lam, Giles S.H. Yeo, Kimberly M. Alonge, Huiliang Li, William D. Richardson, Mark L. Evans, Clemence Blouet. Preprint.   https://doi.org/10.1101/2024.09.10.612227.

Glucose-Dependent Insulinotropic Polypeptide Receptor Signalling in Oligodendrocytes Increases the Weight Loss Action of GLP-1R Agonism. Robert Hansford, Sophie Buller, Anthony H. Tsang, Simon Benoit, Anna Roberts, Emmy Erskine, Valentina Pirro, Frank Reimann, Noria Harada, Nobuya Inagaki, Alice Adrienssens, Ricardo Samms, Clemence Blouet. Preprint. http://dx.doi.org/10.2139/ssrn.4704168

Median eminence myelin continuously turns over in adult mice. Buller S, Kohnke S, Hansford R, Shimizu T, Richardson WD, Blouet C. Mol Metab, 2023. PMID: 36739968 PMCID: PMC9950957

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 Report, 2021 PMID: 34260928 PMCID: PMC8293628

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. Heeley N,  Kirwan P,   Darwish T,   Arnaud M,  Evans ML,   Merkle FT,   Reimann F,   Gribble FM,   Blouet C. 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. Burke LK,   Darwish T,  Cavanaugh AR ,  Virtue S,  Roth E,  Morro J,  Liu SM ,  Xia J,  Dalley JW,  Burling K ,  Chua S,  Vidal-Puig A ,  Schwartz GJ ,  Blouet C. eLife, 2017 PMID: 28532548 PMCID: PMC5441868

Programme Leader, MRC Metabolic Diseases Unit
Institute of Metabolic Science
Department of Clinical Biochemistry, University of Cambridge
photo of clemence blouet

Contact Details

Classifications: 
College: 
Clare Hall