A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice

Rogier L.C. Plas, Mieke Poland, Joyce Faber, Josep Argilès, Miriam van Dijk, Alessandro Laviano, Jocelijn Meijerink, Renger F. Witkamp, Ardy van Helvoort, Klaske van Norren

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

Original languageEnglish
Article number4978
JournalInternational Journal of Molecular Sciences
Volume20
Issue number20
DOIs
Publication statusPublished - 9 Oct 2019

Fingerprint

diets
leucine
Fish Oils
fishes
Hypercalcemia
Parathyroid Hormone-Related Protein
Nutrition
Leucine
Bearings (structural)
Fish
Docosahexaenoic Acids
mice
Tumors
tumors
hormones
oils
Diet
acids
Acids
Eicosapentaenoic Acid

Keywords

  • cachexia
  • fish oil
  • hypercalcemia
  • leucine
  • PTHrP

Cite this

@article{39aa7954818642ea926a3f29cfaab600,
title = "A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice",
abstract = "BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.",
keywords = "cachexia, fish oil, hypercalcemia, leucine, PTHrP",
author = "Plas, {Rogier L.C.} and Mieke Poland and Joyce Faber and Josep Argil{\`e}s and {van Dijk}, Miriam and Alessandro Laviano and Jocelijn Meijerink and Witkamp, {Renger F.} and {van Helvoort}, Ardy and {van Norren}, Klaske",
year = "2019",
month = "10",
day = "9",
doi = "10.3390/ijms20204978",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",
number = "20",

}

A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice. / Plas, Rogier L.C.; Poland, Mieke; Faber, Joyce; Argilès, Josep; van Dijk, Miriam; Laviano, Alessandro; Meijerink, Jocelijn; Witkamp, Renger F.; van Helvoort, Ardy; van Norren, Klaske.

In: International Journal of Molecular Sciences, Vol. 20, No. 20, 4978, 09.10.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice

AU - Plas, Rogier L.C.

AU - Poland, Mieke

AU - Faber, Joyce

AU - Argilès, Josep

AU - van Dijk, Miriam

AU - Laviano, Alessandro

AU - Meijerink, Jocelijn

AU - Witkamp, Renger F.

AU - van Helvoort, Ardy

AU - van Norren, Klaske

PY - 2019/10/9

Y1 - 2019/10/9

N2 - BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

AB - BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

KW - cachexia

KW - fish oil

KW - hypercalcemia

KW - leucine

KW - PTHrP

U2 - 10.3390/ijms20204978

DO - 10.3390/ijms20204978

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 20

M1 - 4978

ER -