Research Groups > Genes and Metabolism Metabolic Signalling

“Our research focuses on the roles of hormone and nutrient-regulated signalling pathways in type II diabetes, obesity and age-related diseases”

Our work investigates the signalling processes in the central nervous system that regulate energy homeostasis and their contribution to diseases such as obesity and type II diabetes. For example, we have identified key roles for insulin receptor substrate (IRS) proteins and AMP-activated protein kinase (AMPK) in the regulation of food intake and body-weight. We have also shown that such signalling pathways regulate mammalian longevity and resistance to the diseases of ageing. Our work will continue to identify the cellular and physiological mechanisms that control energy balance and explore the mechanisms by which mammalian longevity is regulated with regards to the pathogenesis of metabolic and age-related disease.

arcuate nucleus of the hypothalamus
Figure: A coronal section through the arcuate nucleus of the hypothalamus showing pro-opiomelanocortin (POMC) neurons expressing green fluorescent protein transduced with an adenovirus expressing channelrhodopsin and mCherry (red). POMC neurons co-expressing the virus appear yellow.

 Metabolic Signalling
Group head

Dominic Withers

Telephone 33014
Group members

Agharul Choudhury (Dr)

Darran Hardy

Elaine Irvine (Dr)

Steve Millership (Dr)

Silvia Pedroni

Kaisa Piipari (Dr)

Marie-Therese Rached

Eleanor Sandhu

Chain-Florey Fellow

Mark Smith (Dr)

Nadia Tyler-Rubinstein

Admin contact

Claire Smith (Miss)

Telephone 38592
Selected publications
Claret, M., Smith, M. A., Knauf, C., Al-Qassab, H., Woods, A., Heslegrave, A., Piipari, K., Emmanuel, J. J., Colom, A., Valet, P., Cani, P. D., Begum, G., White, A., Mucket, P., Peters, M., Mizuno, K., Batterham, R. L., Giese, K. P., Ashworth, A., Burcelin, R., Ashford, M. L., Carling, D., Withers, D. J. (2011). Deletion of lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice. Diabetes 60, 735–745. Abstract

Al-Qassab, H., Smith, M. A., Irvine, E. E., Guillermet-Guibert, J., Claret, M., Choudhury, A. I., Selman, C., Piipari, K., Clements, M., Lingard, S., Chandarana, K., Bell, J. D., Barsh, G. S., Smith, A. J., Batterham, R. L., Ashford, M. L., Vanhaesebroeck, B., Withers, D. J. (2009). Dominant role of the p110β isoform of PI3K over p110α in energy homeostasis regulation by POMC and AgRP neurons. Cell Metabolism 10, 343–354. Abstract

Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., Woods, A., Robinson, I. C. A., Schuster, E., Batterham, R. L., Kozma, S. C., Thomas, G., Carling, D., Okkenhaug, K., Thornton, J. M., Partridge, L., Gems, D., Withers, D. J. (2009). Ribosomal protein s6 kinase 1 signaling regulates mammalian life span. Science 326, 140–144. Abstract

Selman, C., Lingard, S., Choudhury, A. I., Batterham, R. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., Piper, M. D., Al-Qassab, H., Speakman, J. R., Carmignac, D., Robinson, I. C. A., Thornton, J. M., Gems, D., Partridge, L. and Withers, D. J. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. (2008). FASEB J. 22:807–18. Abstract

Claret, M., Smith, M. A., Batterham, R. L., Selman, C., Choudhury, A. I., Fryer, L. G. D., Clements, M., Al-Qassab, H., Heffron, H., Xu, A. W.,. Speakman, J. R., Barsh, G. S., Viollet, B., Vaulont, S., Ashford, M. L. J., Carling, D. and Withers, D. J. (2007). AMPK is essential for energy homeostasis regulation and glucose-sensing by POMC and AgRP neurons. Journal of Clinical Investigation 117, 2325–2336. Abstract

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