Kisspeptin - a dual physiological role in the hypothalamic control of reproduction
Final Report Abstract
The applicant’s main project during her fellowship at Imperial College under the supervision of Dr James Gardiner dealt with the function of thyroid hormone signalling in the hypothalamus on feeding control and energy homeostasis. The work demonstrates the essential role of TRâ in the VMN in the mediation of food intake and body weight. The profound hyperphagia and obesity which arise following intra- VMN TRâ knock down are as pronounced as some of the most prominent transgenic models of disruption within hypothalamic appetite circuits. Although the findings described are not immediately translatable to the treatment of human obesity, as our understanding of the central energy regulating pathways develops, so too does the possibility of targeted anti-obesity drug therapy. Future work will further augment our understanding of the role of TRâ in the VMN as a key player in the regulation of energy homeostasis. Based upon the acquired scientific knowledge and few valuable technical skills during this work, including amongst others the preparation of Cre-expressing recombinant viral vectors and stereotaxic viral microinjections, the applicant was lucky to acquire further funding for a subsequent project attempting to validate and essentially further characterize now the function and underlying mechanisms of thyroid hormone and TRa signalling on hypothalamic control of metabolic action and feeding regulation. In summary, the applicant has acquired during her fellowship some deeper insights into diverse obesity-related scientific approaches, including both the angle of the central nervous feeding centres and of the small intestinal gut hormones and their modifications by bariatric surgery. She intends to deal now with the still widely neglected issue of the underlying mechanisms through which bariatric surgery modifies specific CNS feeding circuits as a postulated prerequisite for sustained weight reduction beyond alimentary restriction and malabsorption.
Publications
- Exogenous Peptide YY 3–36 and Exendin-4 further decrease Food Intake, while Octreotide increases Food Intake in Rats after Roux-en-Y Gastric Bypass. Int J Obes (Lond), 2011 Jun 21
Wiebke Fenske, Marco Bueter, Alexander D. Miras, Mohammed A Ghatei, Stephen R. Bloom, Carel W. le Roux
(See online at https://doi.org/10.1038/ijo.2011.126) - Can a protocol for glycaemic control improve type 2 diabetes outcomes after gastric bypass? Obes Surg, 2012 Jan;22(1):90-6
Wiebke K. Fenske, Dimitri J. Pournaras, Erlend T. Aasheim, Alexander D. Miras, Nicola Scopinaro, Samantha Scholtz, Carel W. le Roux
(See online at https://doi.org/10.1007/s11695-011-0543-6) - Effect of Bariatric Surgery Induced Weight Loss on Renal-, Systemic Inflammation and Blood Pressure: A 12-Month Prospective Study. Surg Obes Relat Dis. 2012 Apr 10. [Epub ahead of print]
Wiebke Fenske, Sukhpreet Dubb, Marco Bueter, Florian Seyfried, Karishma Patel, Frederick W. K. Tam, Andrew H. Frankel, Carel W. le Roux
(See online at https://doi.org/10.1016/j.soard.2012.03.009) - Urinary phenotyping indicates weight loss independent metabolic effects of Roux-en-Y Gastric Bypass in mice. J Proteome Res. 2013 Jan 21. [Epub ahead of print]
Seyfried F, Li JV, Miras AD, Cluny NL, Lannoo M, Fenske WK, Sharkey KA, Nicholson JK, Le Roux CW, Holmes E.
(See online at https://doi.org/10.1021/pr300909v)
