MCH and orexin gene expression in a murine model of cancer anorexia cachexia syndrome

Morden, Caleb Christopher (2021) MCH and orexin gene expression in a murine model of cancer anorexia cachexia syndrome. Masters thesis, Memorial University of Newfoundland.

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Abstract

Cancer anorexia/cachexia syndrome (CACS) is defined as a severe loss of appetite and body weight that results in a significant increase in cancer-related mortality. CACS is thought to involve the hypothalamus, the brain region that controls energy homeostasis. Melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus are involved in regulating appetite and body weight. However, their role in CACS is unclear. Here, the Lewis-Lung Carcinoma (LLC) mouse model was used to characterize CACS. Additionally, using quantitative RT-PCR we investigated the levels of MCH and orexin gene expression in the hypothalami of LLC tumour-bearing mice. We found that injection of 0.5x106 LLC cells results in the most robust CACS with consistent anorexia and cachexia. In these mice, orexin mRNA expression was significantly reduced which correlated with food intake. Alternatively, in mice displaying cachexia only, MCH and orexin gene expression were positively correlated with body weight gain. Specifically, tumour-bearing mice with upregulated MCH or orexin mRNA expression did not lose weight, while those that failed to increase these factors lost weight. These results indicate that MCH and orexin may play a protective role against tumour-induced weight loss, while decreased orexin gene expression may contribute to anorexia in tumour-bearing mice. Overall, these findings support the idea that the MCH and orexin system may provide a potential therapeutic target for CACS.

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