Hypothalamic food intake regulation in a cancer‐cachectic mouse model

Journal of Cachexia, Sarcopenia and Muscle

Dwarkasing Jvalini T.²  van Dijk Miriam⁵  Dijk Francina J.⁵  Boekschoten Mark V.⁴  Faber Joyce⁵  Argilès Josep M.³  Laviano Alessandro¹  Müller Michael⁴  Witkamp Renger F.² 

[1] Department of Clinical Medicine, Sapienza University, Rome;Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Wageningen;Cancer Research Group, Departament de Bioquímica i Biologia Molecular, University of Barcelona, Barcelona;Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen;Nutricia Advanced Medical Nutrition, Nutricia Research for Specialised Nutrition, Utrecht

关键词: Cancer;    Hypothalamus;    Appetite;    Serotonin;    Transcriptomics;    Anorexia;   

DOI  :  10.1007/s13539-013-0121-y

来源: Wiley

【 摘 要 】

Abstract

Background

Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore, studying changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite-regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth.

Methods

C26-colon adenocarcinoma cells were subcutaneously inoculated in 6 weeks old male CDF1 mice. Body weight and food intake were measured three times a week. On day 20, hypothalamus was dissected and used for transcriptomics using Affymetrix chips.

Results

Food intake increased significantly in cachectic tumour-bearing mice (TB), synchronously to the loss of body weight. Hypothalamic gene expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls.

In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake.

Conclusions

Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Further research has to reveal whether targeting these systems will be a good strategy to avoid the development of cancer-induced eating disorders.

Electronic supplementary material

The online version of this article (doi:10.1007/s13539-013-0121-y) contains supplementary material.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.