Obesity and reproduction

Regulatory Peptides + Hypothalamic Growth Regulatory peptides, both hormones and neurotransmitters, are the key expertise of this group of about 30 scientists and scientists in training. These signals are crucial to the control of mammalian energy balance.

We use multiple techniques, from targeted adult gene manipulation through hypothalamic explants to human infusion studies, to demonstrate the workings of the hypothalamic circuits regulating appetite and energy expenditure.

We have discovered the important role of peripheral peptide hormonal signals, for example from the gut, in regulating appetite. This is being exploited to identify the cause of excessive (or deficient) fat stores in man. These gut hormones are being used to develop powerful new ways of regulating appetite. They have the advantage that they appear safe for long term therapy. With over 1,000 people dying prematurely from obesity in the UK each week, and no effective treatment, such original approaches are long overdue and spur on our work.

Our group has performed a number of pioneering 'first-to-man' infusions of peptide hormones, including GLP-1, peptide YY, oxyntomodulin and kisspeptin. The group also has an outstanding track record in performing basic scientific research in molecular biology (Gardener, Kong Biochem Biophys Res com, 2005) and functional imaging (Chaudhri et al. J Neuroscince, 2007).

Selected publications:

Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin C, Wren AM, Brynes A, Low M, Ghatei M, Cone R & Bloom SR.Gut hormone PYY3-36 physiologically inhibits food intake.Nature2002, 418:650-654.

Dhillo WS, Small CJ, Jethwa PH, Russell SH, Gardiner JV, Bewick GA, Seth A, Murphy KG, Ghatei MA, Bloom SR. Paraventricular nucleus administration of calcitonin gene-related peptide inhibits food intake and stimulates the hypothalamo-pituitary-adrenal axis. Endocrinology 2003 Apr;144(4):1420-5

Lord G, Matarese-G, Howard JK, Baker RJ, Lechler-RI. Leptin modulates the T-cell immune response and reverses starvation induced immunosuppreression. Nature

Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Ghatei,MA, Bloom,SR role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379(6560):69-72

Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy, K. G., Dhillo, W. S., Ghatei, M. A., and Bloom, S. R. Ghrelin enhances appetite and increases food intake in humans. J.Clin.Endocrinol.Metab2001, 86: 5992-5995.

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