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At least 793 records · Page 44Linked to original sources
PubMed2001

Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.

Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

Adipose Tissue↗
PubMed1992

A review of cancer cachexia and abnormal glucose metabolism in humans with cancer.

In 1919, glucose intolerance became the earliest recognized metabolic abnormality in cancer patients. Prior to the development of severe malnutrition, colon, gastric, sarcoma, endometrial, prostate, localized head, neck, and lung cancer patients had many of the metabolic abnormalities of type II (noninsulin dependent) diabetes mellitus. These metabolic abnormalities include glucose intolerance, an increase in both hepatic glucose production (HGP) and glucose recycling, and insulin resistance. In a study of over 600 cancer patients, a diabetic pattern of glucose tolerance test was noted in over one-third of the patients. An increased rate of HGP, commonly seen in diabetics, has been noted in almost all types of cancer patients studied to date. Etiology of the increased glucose production in the cancer patient is not known, but abnormalities in the counter regulatory hormones, especially growth hormone, may contribute to the development of abnormal glucose metabolism. A second possible stimulus for the increase in HGP could be the glucose needs of the tumor. Abnormally high glucose utilization rates in small amounts of tumor tissue have recently been described. This suggests that small tumors may have large needs for glucose calories. An increase in anaerobic glycolysis in the tumor tissue can increase lactate production in the tumor-bearing human, thus supplying substrate to the liver to increase glucose production rates. In this paper, the nature of abnormal glucose metabolism in cancer patients is described.

Cachexia↗
PubMed1996

Studies on the lipid metabolism of Walker 256 tumour-bearing rats during the development of cancer cachexia.

Aspects of the lipid metabolism of Walker 256 carcinosarcoma-bearing cachectic rats (TB) were investigated during a 14 day interval of tumour growth. Food intake and body weight of the TB rats were reduced by 18% and 13%, respectively, on day 14, as compared with non-tumour-bearing animals. The tumour burden then, corresponded to 19% of total body weight. The total fat content was not different in the liver, heart, carcass, epididymal (EAT) and retroperitoneal (RPAT) adipose tissues of the two groups. The brown adipose tissue (BAT) and skeletal muscle (gastrocnemius-SM) of the TB rats had increased levels of fat (23% and 200%, respectively). Enteral absorption of 14C-triolein was decreased in the TB rats, but the liver, heart, and SM of these animals incorporated more radiolabelled lipid than the control animals, while the adipose tissues exhibited a decreased incorporation of radioactivity in relation to controls. More lipid was incorporated into the VLDL fraction secreted by the liver of TB rats, which exhibited a different distribution of the incorporated 14C-oleate in the various lipid subfractions. Ultrastructural studies showed that the hepatocytes of the TB rats had a greater incidence of lipid droplets in the cytoplasm.

Adipose Tissue↗
PubMed1988

Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism.

The aim of this study was to determine whether a ketogenic diet could decrease nitrogen losses in cachectic cancer patients and at the same time reduce the supply of glucose for tumor energy metabolism. Five patients with malignant disease and severe weight loss (mean 32%) were fed via a fine bore nasogastric tube. A normal diet was given for 6 d and this was followed by 7 d of an isonitrogenous, isocaloric, ketogenic diet. Both diets were well tolerated. At 7 d the mean ketone body concentration in the blood of patients fed the ketogenic diet was 1.21 +/- 0.33 mM. This ketosis was associated with a significant reduction of the concentration in blood of glucose, lactate, and pyruvate (p less than 0.05). There was, however, no significant alteration in host N balance or whole-body protein synthesis, degradation, or turnover rates. Whether the change from glucose- to fat-derived energy substrates might reduce tumor growth rates in the long term remains to be determined.

Acidosis↗
PubMed1995

The use of bioelectrical impedance analysis to predict total body water in patients with cancer cachexia.

The applicability of bioelectrical impedance analysis (BIA) to predict total body water (TBW) was assessed in 16 underweight [< 95% of ideal body weight (IBW)] and 25 normal-weight (> 95% of IBW) cancer patients. Although height2/resistance (ht2/R) proved to be a strong single predictor of TBW measured by deuterium dilution in both groups (normal-weight patients: r2 = 0.85, SEE 2.16 L; underweight patients: r2 = 0.86, SEE 2.24 L), TBW would be significantly overestimated in the underweight group if the prediction formula developed in the normal-weight group was used [bias 1.67 L (5%), 95% CI 0.20-3.15 L]. A systematic overestimation of TBW in the underweight patients was also found when TBW was predicted in our two patient groups by several previously published BIA formulas developed in normal-weight individuals. We conclude therefore, that although a similar relationship is found between ht2/R and TBW in normal-weight and underweight cancer patients, single-frequency BIA overestimates TBW in underweight patients when prediction formulas are used that have been developed in normal-weight subjects.

Adenocarcinoma↗
PubMed1992

Cachexia and cancer: a clinician's view.

The cancer-related cachexia/anorexia syndrome is not well understood. It is related to several factors like metabolic changes, tumor types, and disease extent and is frequently accompanied by decreased performance status. An important aspect of anorexia is the psychosocial problem: the patient is unable to join the family for meals precisely when he or she most needs familial support. Several randomized studies have shown that megestrol acetate, possibly in a dose-dependent fashion, can improve appetite and lead to weight gain. This effect seems to be most prevalent in patients with breast cancer and also occurs in the absence of a tumor response. We have retrospectively analyzed 176 patients with cancer types other than breast cancer who received only palliative treatment. The patients were treated with megestrol acetate (160 mg tid) because they complained of anorexia. After 10 days of treatment, megestrol acetate was continued only in those patients whose appetite and/or general well-being improved. Fifty-seven patients (32%) experienced such an improvement and asked for continuation of therapy. Many basic questions are still unanswered; nonetheless, from a practical clinical view it seems worthwhile to offer anorectic patients a chance to improve, especially since side effects of megestrol acetate are absent or mild, and the distinction between responders and nonresponders can be made by 10 days of treatment.

Anorexia↗
PubMed1995

Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support.

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing either ornithine alpha-ketoglutarate, which has been used in other catabolic states (i.e. injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progressive anorexia, negative nitrogen balance, and body and tissue wasting. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the tumor on its host. We hypothesized that capture of amino acids by the tumor limited the efficacy of supplemental nutrition here and in published reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that a 3-wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equivalent to approximately 70% of the host's daily protein intake. To parallel the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treated by excision of the tumor at a limited stage of the disease. Rats received 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively. Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed rats showed a more positive nitrogen balance, higher concentrations of glutamine and branched-chain amino acids in muscle, and accelerated protein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underline the need for clinically relevant animal models for further studies.

Amino Acids↗
PubMed1997

Inflammatory and hormonal mediators of cachexia.

Body composition is a reflection of the metabolic state of the organism. However, because the time course of change in body composition is slower than that of metabolic processes, measurement of body composition offers a unique way of assessing the organism's physiologic status. The hormonal and immune mediators that control metabolism, and thus body composition, can be divided into three categories: day-to-day regulators (insulin and glucagon), life cycle-related hormones (estrogens and androgens, growth hormone, prolactin, thyroid hormones, catecholamines, corticosteroids) and immunologic mediators (the cytokines interleukin-1, tumor necrosis factor, and interleukin-6). Although the cytokines can clearly drive metabolism and thus body composition in various illnesses, it is not yet clear whether they also play a homeostatic role in the age-related changes in body composition that we now call sarcopenia.

Aging↗