Energy expenditure and protein synthesis rates in an animal model of cancer cachexia

doi:10.1016/0261-5614(91)90077-P

Clinical Nutrition

Volume 10, Issue 1, February 1991, Pages 23-29

https://doi.org/10.1016/0261-5614(91)90077-P Get rights and content

Abstract

Food intake and energy expenditure of cachectic tumour bearing mice were measured during the course of weight loss. Four weeks after implantation of the MAC-16 tumour the body weight was reduced by 20%, there was no significant reduction in food intake, and body composition analysis revealed that both body fat and protein mass were decreased.

Oxygen consumption and carbon dioxide production were measured over a 24h period both before and at weekly intervals after tumour implantation. There was a gradual increase in the rates of both oxygen consumption and carbon dioxide production per gram body weight. Similarly, energy expenditure per gram body weight was increased during the 3rd (11%) and 4th (23%) weeks. In contrast, the food intake per gram body weight was unchanged during the first three weeks and increased by only 8% during the 4th week.

Despite the development of cachexia, rates of protein synthesis in the liver, heart, kidney and skeletal muscle were the same four weeks after tumour implantation as those in non-tumour bearing mice.

Thus, in this murine model of cancer cachexia a negative energy balance resulted from failure of food intake to compensate for increased energy demands. These findings point to the unique pattern of metabolic alterations which occur in different models of cancer cachexia.

References (30)

SD Morrison
Control of food intake in cancer cachexia: A challenge and a tool
Physiology and Behaviour
(1976)
E Eden et al.
Whole body tyrosine flux in relation to energy expenditure in weight-losing cancer patients
Metabolism
(1984)
M Jeevanandam et al.
Cancer cachexia and protein metabolism
Lancet
(1984)
OH Lowry et al.
Protein measurement with folin phenol reagent
Journal of Biological Chemistry
(1951)
L Lindmark et al.
Resting energy expenditure in malnourished patients with and without cancer
Gastroenterology
(1984)
S Warren
The immediate causes of death in cancer
American Journal of Medical Science
(1932)
J Inagaki et al.
Causes of death in cancer patients
Cancer
(1974)
D Heber et al.
Metabolic abnormalities in the cancer patient
Cancer
(1985)
MF Brennan
Uncomplicated starvation versus cancer cachexia
Cancer Research
(1977)
DH Lawson et al.
Metabolic approaches to cancer cachexia
Annual Review of Nutrition
(1982)

RW Begg et al.

Systematic effects of tumours in force fed rats

Cancer Research

(1951)

JF Moley et al.

Body composition changes in rats with experimental cancer cachexia: Improvement with exogenous insulin

Cancer Research

(1988)

M Recheigl et al.

Studies on the cachexia of tumour bearing animals 1. Body weight changes, carcass composition and metabolic studies

Cancer Research

(1961)

SB Heymsfield et al.

Tissue components of weight loss in cancer patients: A new method of study and preliminary observations

Cancer

(1985)

K Lundholm et al.

A comparative study of the influence of malignant tumour on host metabolism in mice and man

Cancer

(1978)

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^†: Present address: University Department of Surgery, Royal Infirmary, Edinburgh, UK

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Energy expenditure and protein synthesis rates in an animal model of cancer cachexia

Abstract

Physiology and Behaviour

Metabolism

Lancet

Journal of Biological Chemistry

Gastroenterology

The immediate causes of death in cancer

American Journal of Medical Science

Causes of death in cancer patients

Cancer

Metabolic abnormalities in the cancer patient

Cancer

Uncomplicated starvation versus cancer cachexia

Cancer Research

Metabolic approaches to cancer cachexia

Annual Review of Nutrition

Systematic effects of tumours in force fed rats

Cancer Research

Body composition changes in rats with experimental cancer cachexia: Improvement with exogenous insulin

Cancer Research

Studies on the cachexia of tumour bearing animals 1. Body weight changes, carcass composition and metabolic studies

Cancer Research

Tissue components of weight loss in cancer patients: A new method of study and preliminary observations

Cancer

A comparative study of the influence of malignant tumour on host metabolism in mice and man

Cancer