Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus

DE Ganella; GE Callander; S Ma; AL Gundlach; RAD Bathgate; CR Bye

Journal article

Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus

DE Ganella, GE Callander, S Ma, AL Gundlach, RAD Bathgate, CR Bye

Gene Therapy | Published : 2012

DOI: 10.1038/gt.2012.83

Abstract

Relaxin-3 is a neuropeptide that is abundantly expressed by discrete brainstem neuron populations that broadly innervate forebrain areas rich in the relaxin-3 G-protein-coupled-receptor, RXFP3. Acute and subchronic central administration of synthetic relaxin-3 or an RXFP3-selective agonist peptide, R3/I5, increase feeding and body weight in rats. Intrahypothalamic injection of relaxin-3 also increases feeding. In this study, we developed a recombinant adeno-associated virus 1/2 (rAAV1/2) vector that drives expression and constitutive secretion of bioactive R3/I5 and assessed the effect of intrahypothalamic injections on daily food intake and body weight gain in adult male rats over 8 weeks. ..

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University of Melbourne Researchers

Andrew Gundlach Author

Ross Bathgate Author

Chris Bye Author

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Grants

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

We thank Dr Melanie White, Tania Ferraro and Professor Michael McKinley for technical assistance, Dr Changlu Liu (Johnson & Johnson Pharmaceutical Research and Development LLC, San Diego, CA, USA) for provision of the pCMVSportR3/I5 construct, Professor Thomas McCown (University of North Carolina, Chapel Hill, NC, USA) for the kind gift of the TR-FIB-GFP construct, Dr Michael Mathai (Victoria University, Melbourne, VIC, Australia) for the use of the Echo-MRI Body Composition Analyser and Prof. Geoffrey Tregear for his continuing support. This research was supported by National Health and Medical Research Council of Australia Project Grants 509246 (ALG) and 1005988 (ALG, RADB), and by the Victorian Government Operational Infrastructure Support Programme. DEG is the recipient of Commonwealth Australian Postgraduate Award and GEC was the recipient of a University of Melbourne Research Scholarship. SM and ALG and RADB are recipients of NHMRC (Australia) Training and Research Fellowships, respectively.