Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling

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Abstract

Background. Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.
LanguageEnglish
Pages84-94
JournalJournal of cachexia, sarcopenia and muscle
Volume6
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Serotonin
Eating
Neuropeptide Y
Neoplasms
Lewis Lung Carcinoma
Cachexia
Anorexia
Hypothalamus
Appetite Regulation
Growth
Malnutrition
Colon
Adenocarcinoma
Quality of Life
Gene Expression
Cell Line

Keywords

  • integrin-linked kinase
  • rat skeletal-muscle
  • oxidative stress
  • soleus muscle
  • ubiquitin-proteasome
  • myoblast differentiation
  • apoptotic pathways
  • connective-tissue
  • tibialis anterior
  • atrophy

Cite this

@article{a2475b4ebe1447b1b85996a004947cea,
title = "Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling",
abstract = "Background. Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.",
keywords = "integrin-linked kinase, rat skeletal-muscle, oxidative stress, soleus muscle, ubiquitin-proteasome, myoblast differentiation, apoptotic pathways, connective-tissue, tibialis anterior, atrophy",
author = "J.T. Dwarkasing and M.V. Boekschoten and R.F. Witkamp and {van Norren}, K.",
year = "2015",
doi = "10.1002/jcsm.12008",
language = "English",
volume = "6",
pages = "84--94",
journal = "Journal of cachexia, sarcopenia and muscle",
issn = "2190-5991",
publisher = "Wiley",
number = "1",

}

TY - JOUR

T1 - Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling

AU - Dwarkasing, J.T.

AU - Boekschoten, M.V.

AU - Witkamp, R.F.

AU - van Norren, K.

PY - 2015

Y1 - 2015

N2 - Background. Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.

AB - Background. Anorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.

KW - integrin-linked kinase

KW - rat skeletal-muscle

KW - oxidative stress

KW - soleus muscle

KW - ubiquitin-proteasome

KW - myoblast differentiation

KW - apoptotic pathways

KW - connective-tissue

KW - tibialis anterior

KW - atrophy

U2 - 10.1002/jcsm.12008

DO - 10.1002/jcsm.12008

M3 - Article

VL - 6

SP - 84

EP - 94

JO - Journal of cachexia, sarcopenia and muscle

T2 - Journal of cachexia, sarcopenia and muscle

JF - Journal of cachexia, sarcopenia and muscle

SN - 2190-5991

IS - 1

ER -