Loss of acetoacetate coenzyme A transferase activity in tumours of peripheral tissues

Tisdale, M. J.; Brennan, R A

doi:10.1038/bjc.1983.38

Cited by 90 publications

(69 citation statements)

References 19 publications

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“…However, no activity of the enzyme 3-ketoacid CoA transferase was detected. A similar distribution of enzyme activities has been reported for other tumours of the peripheral tissues (Tisdale & Brennan, 1983). Since activity of the enzyme 3-ketoacid CoA transferase determines the extent to which 3-hydroxybutyrate is used as a metabolic fuel (Williamson et al, 1971) it might be expected that the Walker 256 carcinosarcoma would be unable to metabolize ketone bodies.…”

Section: Discussionmentioning

confidence: 68%

“…Determination of tumour enzyme activities The activities of 3-hydroxybutyrate dehydrogenase, acetyl CoA acetyltransferase and 3-ketoacid CoA transferase were determined spectrophotometrically as described previously (Tisdale & Brennan, 1983 Food intakes were measured daily and all animals had attained a stable food intake by the seventh day. On the eighth day, total body nitrogen was determined by neutron activation analysis in vivo and this was followed by either tumour implantation (Groups A, B, C) or sham operation (Group D).…”

Section: Animalsmentioning

confidence: 99%

“…Tumour cells are known to have a high rate of glucose consumption, show increased rates of anaerobic glycolysis, and to be susceptible to carbohydrate deprivation (see Demetrakopoulos & Brennan, 1982). Alternatively, many poorly differentiated tumours lack certain key mitochondrial enzymes and have thus largely lost the ability to use fat or ketone bodies for energy production (Cederbaum & Rubin, 1976, Tisdale & Brennan, 1983. Thus it has been proposed that ketone bodies might be administered as a "host- specific" energy substrate (Tisdale & Brennan, 1983).…”

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confidence: 99%

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Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Fearon¹,

Tisdale²,

Preston³

et al. 1985

Br J Cancer

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Section: Discussionmentioning

confidence: 68%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

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Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Fearon¹,

Tisdale²,

Preston³

et al. 1985

Br J Cancer

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“…It is clear that the wasting seen in association with cancer is different from uncomplicated starvation (Stein, 1978;Conyers et al, 1979a,b;Magee et al, 1979;Brennan, 1981) but little is known about the role of ketone bodies in this state. The host's ability to become ketonaemic may well influence his survival in terms of energy conservation, as in uncomplicated starvation, and decreased tumour progression due to either the inability of tumours to use ketone bodies as fuels or the inhibitory effects of ketone bodies on malignant cell growth (Conyers et al, 1979a;Magee et al, 1979;Tisdale & Brennan, 1983).…”

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confidence: 99%

The metabolic response of tumour-bearing mice to fasting

Rofe¹,

Porter²,

Bais³

et al. 1985

Br J Cancer

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Summary The suggestion that the ketonaemic response to fasting may be altered in the tumour-bearing state was investigated by studying the metabolism of fasted C57/BL6j mice bearing transplanted B16 melanomas. Ketone body (D-3-hydroxybutyrate and acetoacetate) concentrations in the blood of the tumour-bearing mice were significantly increased after a 24h fast compared to control mice with identical dietary histories. Hepatic glycogen levels were lower at the start of the fasting period in the tumour-bearing mice as were the fat stores. The loss of adipose tissue during the fasting period was greater in the tumour-bearing mice. After 48 h of fasting, the ketonaemia was significantly lower in the tumour-bearing mice compared to the appropriate controls. Two distinct metabolic states are indicated in these fasted tumour-bearing mice, one characterised by accelerated ketonaemia, and a later, near terminal stage, where fat deposits are markedly depleted and ketonaemia is decreased.

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“…Ketone bodies might be expected to preserve lean body mass during periods of weight loss and to be poor metabolic substrates for the tumour (Tisdale & Brennan, 1983;Rofe et al, 1986). Additional rationalization for the use of a ketogenic diet for the reversal of the weight loss in cancer cachexia has come from recent studies showing inhibition of lipolytic and proteolytic factors produced by the MAC16 tumour by sodium D-(-)3-hydroxybutyrate (Beck & Tisdale, 1987).…”

Section: Discussionmentioning

confidence: 99%

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

Tisdale

Brennan²

1988

Br J Cancer

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Summary A comparison has been made between the ability of long-chain triglycerides (LCT) and mediumchain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size.Weight loss is a common feature of many neoplastic diseases (De Wys, 1986) and appears to be independent of the tumour burden and often precedes clinical diagnosis. The end result of the continuing decline in nutritional status is the clinical syndrome of cancer cachexia. Patients with weight loss have a poorer response to chemotherapy and a shorter survival time than those without weight loss (De Wys et al., 1980).We have utilized the MAC 16 adenocarcinoma of the mouse colon as an experimental model of human cachexia, where weight loss arises from the metabolic effects of the tumour on the host (Bibby et al., 1987). Animals bearing the MAC16 tumour show weight loss at small tumour burdens (less than 1% of the host weight) and without a reduction in either food or water intake. Weight loss is characterized by a progressive loss of both body fat and muscle dry weight, which increases in direct proportion to the tumour burden (Beck & Tisdale, 1987). Although there is extensive mobilization of body fat reserves ketosis does not occur (Bibby et al., 1987). Ketonuria has also been shown not to occur in cancer patients . Since ketone bodies are believed to play an important role in the regulation of lean body mass during starvation we and others (Tisdale, 1982;Magee et al., 1979;Williamson & Matthaei, 1981) have suggested that a high fat/low carbohydrate ketogenic diet should also preserve lean body mass during cancer cachexia, and would not be expected to be utilized by a poorly vascularized tumour, which would depend primarily on glucose as an energy source. In addition 3-hydroxybutyrate has recently been shown to inhibit the lipolytic and proteolytic factors produced by the MAC16 tumour and which may be responsible for the cachexia (Beck & Tisdale, 1987). Such an approach has been vindicated since mice bearing the MAC16 tumour fed a diet in which up to 80% of the energy was supplied as medium-chain triglycerides (MCT) show a reduction in both the extent of weight loss and tumour weight . A ketogenic diet containing 70% MCT and supplemented with D-3-...

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Loss of acetoacetate coenzyme A transferase activity in tumours of peripheral tissues

Cited by 90 publications

References 19 publications

Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

Failure of systemic ketosis to control cachexia and the growth rate of the Walker 256 carcinosarcoma in rats

The metabolic response of tumour-bearing mice to fasting

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

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