Hypothalamic food intake regulation in a cancer-cachectic mouse model

J.T. Dwarkasing, M. van Dijk, F.J. Dijk, M.V. Boekschoten, J. Faber, J.M. Argiles, A. Laviano, M.R. Müller, R.F. Witkamp, K. van Norren

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)159-169
JournalJournal of cachexia, sarcopenia and muscle
Volume5
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Appetite Regulation
Eating
Neoplasms
Serotonin
Hypothalamus
Hypothalamic Neoplasms
Appetite
Body Weight
Anorexia
Dopamine
Gene Expression
Pro-Opiomelanocortin
Brain
Neuropeptides
Transcriptome
Colon
Adenocarcinoma

Keywords

  • tumor-bearing rats
  • neuropeptide-y
  • colon-26 adenocarcinoma
  • serotonergic system
  • insulin-resistance
  • brain-serotonin
  • murine model
  • amino-acids
  • cachexia
  • mice

Cite this

Dwarkasing, J.T. ; van Dijk, M. ; Dijk, F.J. ; Boekschoten, M.V. ; Faber, J. ; Argiles, J.M. ; Laviano, A. ; Müller, M.R. ; Witkamp, R.F. ; van Norren, K. / Hypothalamic food intake regulation in a cancer-cachectic mouse model. In: Journal of cachexia, sarcopenia and muscle. 2014 ; Vol. 5, No. 2. pp. 159-169.
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title = "Hypothalamic food intake regulation in a cancer-cachectic mouse model",
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",
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Hypothalamic food intake regulation in a cancer-cachectic mouse model. / Dwarkasing, J.T.; van Dijk, M.; Dijk, F.J.; Boekschoten, M.V.; Faber, J.; Argiles, J.M.; Laviano, A.; Müller, M.R.; Witkamp, R.F.; van Norren, K.

In: Journal of cachexia, sarcopenia and muscle, Vol. 5, No. 2, 2014, p. 159-169.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Hypothalamic food intake regulation in a cancer-cachectic mouse model

AU - Dwarkasing, J.T.

AU - van Dijk, M.

AU - Dijk, F.J.

AU - Boekschoten, M.V.

AU - Faber, J.

AU - Argiles, J.M.

AU - Laviano, A.

AU - Müller, M.R.

AU - Witkamp, R.F.

AU - van Norren, K.

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

KW - tumor-bearing rats

KW - neuropeptide-y

KW - colon-26 adenocarcinoma

KW - serotonergic system

KW - insulin-resistance

KW - brain-serotonin

KW - murine model

KW - amino-acids

KW - cachexia

KW - mice

U2 - 10.1007/s13539-013-0121-y

DO - 10.1007/s13539-013-0121-y

M3 - Article

VL - 5

SP - 159

EP - 169

JO - Journal of cachexia, sarcopenia and muscle

JF - Journal of cachexia, sarcopenia and muscle

SN - 2190-5991

IS - 2

ER -