Poster Presentation The International Congress of Neuroendocrinology 2014

Investigating the contribution of altered metabolic gene expression in obese Kiss1r KO mice. (#153)

Julie-Ann P De Bond 1 , Kristin P Tolson 2 , Alexander S Kauffman 2 , Jeremy T Smith 1
  1. School of Human Sciences, University of Western Australia, Perth, Australia
  2. Department of Reproductive Medicine, University of California San Diego, La Jolla, CA, USA

Kisspeptin controls reproduction by stimulating GnRH neurons via Kiss1r, its receptor. Kiss1r is expressed in other areas of the brain and in peripheral tissues predicating a non-reproductive role. However, this has not been extensively investigated. We have recently examined the role of kisspeptin in energy balance by characterising the metabolic profile of Kiss1r KO mice. These mice developed an obese and diabetic phenotype compared to wild type (WT) littermates. Our aim was to investigate why these Kiss1r KOs develop this phenotype. We hypothesised that expression of hypothalamic metabolic genes will be altered in Kiss1r KOs. Genes examined were neuropeptide Y (Npy), agouti-related protein (Agrp)(both orexigenic neuropeptides), pro-opiomelanocortin (Pomc) and cocaine and amphetamine-related transcript (Cart)(both anorexigenic neuropeptides). Leptin receptor (Lepr), ghrelin receptor (Ghsr) and melanocortin receptor 3 and 4 (Mc3r, Mc4r) were also examined. Hypothalamic samples were obtained from both genders in gonadectomised obese Kiss1r KO and WT mice (20 week old) and also in gonad intact (8 week old) mice at obesity onset. Relative gene expression was quantified by qRT-PCR. There was no significant genotype difference in any of the hypothalamic genes tested. However, there was a trend in female Kiss1r KO mice for a decrease in Pomc gene expression compared to WT females (p=0.07). We subsequently examined key metabolic genes in peripheral tissues of gonad intact mice. In the liver, genes implicated in gluconeogenesis and glycogenolysis were investigated. In both male and female Kiss1r KO mice, there was a significant decrease (p<0.05) in the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase (Pck1) compared to WT. Thus, it is possible that the obesity in Kiss1r KO mice is due in part to altered liver glucose metabolism. Overall, these data reveal either a direct or indirect mechanism of kisspeptin signalling on peripheral glucose metabolism with probable implications to energy balance and obesity.