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

Fearon, K. C. H.; Tisdale, M. J.; Preston, Thomas C.; Plumb, Jane A.; Calman, Kenneth C.

doi:10.1038/bjc.1985.153

Cited by 24 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although blood ketone levels were elevated under restriction of either diet, elevated ketone levels alone could not account for reduced tumour growth because tumour growth was rapid in the UR-KD group despite the presence of high ketone levels. These findings support the previous observations of Fearon et al (1985), who showed that the failure of a KD to restrict growth of the Walker 256 rat tumour resulted from Linear regression analysis of plasma glucose and IGF-1 levels (A), and plasma IGF-1 levels and CT-2A-tumour growth (B) in mice fed with both the SD and KD (n ¼ 23). These analyses included the values for plasma glucose and b-OHB levels of individual mice from both the UR-and R-fed groups.…”

Section: Discussionsupporting

confidence: 90%

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer

et al. 2003

View full text Add to dashboard Cite

Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, b-hydroxybutyrate (b-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

show abstract

Section: Discussionsupporting

confidence: 90%

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Cachexia is a frequent symptom in terminal cancer patients (2). During the establishment of this condition the liver plays some key roles in the induction of the metabolic imbalances of the host, for example by the conversion of lactate to glucose at high rates (29), thereby generating a negative Table 2.…”

Section: Discussionmentioning

confidence: 99%

“…Cachexia is a paraneoplastic syndrome frequently observed in cancer patients (1,2) and tumourbearing animals (3). Its appearance is correlated with the death rate associated with the disease (1).…”

Section: Introductionmentioning

confidence: 99%

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Seelaender¹,

Curi²,

Colquhoun³

et al. 1998

IUBMB Life

View full text Add to dashboard Cite

Summary. The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT IIspecific antibody identified two bands (corresponding to Mr 69,000 and 54,000) in tumourbearing rats whereas only the normal-sized CPT II was present (at the expected Mr 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.

show abstract

“…Such a diet should be achievable clinically since it melanoma deposits in the lungs of C57BL/6 mice by twohas been reported (Phinney et at., 1983) that when normal thirds (Magee et at., 1979) although we have recently human subjects were fed a diet in which 85% of the calories reported a failure of systemic ketosis to control cachexia and were supplied as fat it was well tolerated and there was no growth rate of the Walker 256 carcinosarcoma in rats measurable impairment of hepatic, renal, cardiac or (Fearon et at., 1985). However, the growth of a haemopoietic function.…”

mentioning

confidence: 99%

Reduction of weight loss and tumour size in a cachexia model by a high fat diet

Tisdale¹,

Brennan²,

Fearon³

1987

Br J Cancer

118

View full text Add to dashboard Cite

Summary An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour.

show abstract

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

Cited by 24 publications

References 18 publications

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Reduction of weight loss and tumour size in a cachexia model by a high fat diet

Contact Info

Product

Resources

About