Cancer cachexia and the rate of whole body lipolysis in man

Jeevanandam, Malayappa; Horowitz, Glenn D.; Lowry, Stephen F.; Brennan, Murray F.

doi:10.1016/0026-0495(86)90145-9

Cited by 47 publications

(15 citation statements)

References 27 publications

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“…Our cachectic patients displayed a marked increase in in vivo lipolysis, in accordance with previous observations. [3][4][5][6][7]13 In contrast, adipocyte lipogenesis was unaltered. The latter finding rules out lipogenesis as a factor responsible for the reduced fat cell volume in cancer cachexia.…”

Section: Discussionmentioning

confidence: 99%

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Lipolysis—Not inflammation, cell death, or lipogenesis—Is involved in adipose tissue loss in cancer cachexia

Rydén

Agustsson

Laurencikiene

et al. 2008

Cancer

148

124

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BACKGROUND.Cancer cachexia is an important, negative prognostic marker that has been linked to systemic inflammation and cell death through unclear mechanisms. A key feature of cancer cachexia is loss of white adipose tissue (WAT) because of increased adipocyte lipolysis and possibly reduced lipid synthesis (lipogenesis). In this study, the authors investigated whether alterations in fat cell numbers, lipogenesis, or cytokine and/or leukocyte infiltration could account for some of the functional changes observed in WAT in cancer cachexia.METHODS.Blood and subcutaneous WAT samples were obtained from a 10 weight‐stable patients, from 13 weight losing (cachexia) patients with cancer, and from 5 patients without cancer (noncancer patients) who initially were classified with cancer.RESULTS.Systemic inflammation (increased circulating levels of interleukin 6 [IL‐6]) and enhanced lipolysis were confirmed in the cachectic patients compared with the other patients. However, the messenger RNA expression of IL‐6 and other cytokine or leukocyte markers, as well as WAT secretion of IL‐6, were not altered in the patients with cachexia. Thus, the elevated serum levels of IL‐6 that were observed in cachexia were not derived from WAT. Insulin‐induced lipogenesis in adipocytes from patients with cachexia was the same as that in adipocytes from patients with weight‐stable cancer and from noncancer patients (2.5‐fold maximal stimulation; half‐maximum effective concentration, ∼0.03 nmol/L). Fat cell size was decreased but adipocyte numbers were normal in cancer patients with cachexia, suggesting that there was no major fat cell death.CONCLUSIONS.The current findings indicated that subcutaneous WAT does not contribute to the systemic inflammatory reaction and does not induce adipocyte insulin resistance in cancer cachexia. Moreover, increased fat cell lipolysis, not reduced lipogenesis or adipocyte cell death, appeared to be the primary cause of fat loss in this condition. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

“…5 Conversely, it has been demonstrated that increased in vivo lipolysis, resulting in loss of lipids from adipose tissue, is a key factor promoting adipose cachexia in cancer patients 3,4,6,7 that is independent of malnutrition. [8][9][10][11] Several mechanisms promoting adipocyte lipolysis have been proposed.…”

mentioning

confidence: 99%

Lipolysis—Not inflammation, cell death, or lipogenesis—Is involved in adipose tissue loss in cancer cachexia

Rydén

Agustsson

Laurencikiene

et al. 2008

Cancer

148

124

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“…Thus the elaboration of a lipolytic factor may be essential for the growth and reproduction of neoplastic cells. However, measurement of the rate of whole body lipolysis in man using the glycerol turnover rate has shown no difference between cancer patients and controls (Jeevanandam et al, 1986), although another study using the same technique reported an elevated glycerol turnover in progressive cancer (Eden et al, 1985). Thus, whether the loss of body fat in patients with cancer cachexia is due to a reduced rate of lipogenesis or an augmented lipolysis still remains controversial, although our results would support the latter hypothesis.…”

Section: Serum Lipolytic Activitymentioning

confidence: 99%

Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients

Groundwater

Beck²,

Barton³

et al. 1990

Br J Cancer

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“…Cancer cachexia results in an increase of whole-body lipolysis by an average of 50% [25][26][27][28][29] and the whole-body proteolysis rate is enhanced by an average of 40% [30][31][32][33][34]. To simulate these changes, the model's equations for the lipolysis and proteolysis rates, D F and D P respectively, were adapted as follows:…”

Section: Simulation Of Cancer Cachexiamentioning

confidence: 99%

“…Lipolysis Rate + 50 ± 30% [25][26][27][28][29] Proteolysis Rate + 40 ± 10% [30][31][32][33][34] Cori Cycle + 300 ± 100% [35] Liver Mass Maintained at 1.8 kg [36] Tumor Mass 200 ± 100 g [38,39] …”

Section: Model Parameter Change Versus Normal Referencesmentioning

confidence: 99%

Computational modeling of cancer cachexia

Hall¹,

Baracos²

2008

Current Opinion in Clinical Nutrition and Metabolic Care

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Purpose of review-Measurements of whole-body energy expenditure, body composition, and in vivo metabolic fluxes are required to quantitatively understand involuntary weight loss in cancer cachexia. Such studies are rare because cancer cachexia occurs near the end of life where invasive metabolic tests may be precluded. Thus, models of cancer-associated weight loss are an important tool for helping to understand this debilitating condition.Recent findings-A computational model of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to semi-starvation and re-feeding. Here, this model was used to integrate data on the metabolic changes in patients with cancer cachexia and the resulting computer simulations show how the known metabolic derangements synergize with reduced energy intake to result in a progressive loss of body weight (BW), fat mass (FM), and fat-free mass (FFM). The model was also used to simulate the effects of nutritional support and investigate inhibition of lipolysis versus proteolysis as potential therapeutic approaches for cancer cachexia.Summary-Computational modeling is a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provides a conceptual framework to help understand involuntary weight loss and predict the effects of potential therapies.

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Cancer cachexia and the rate of whole body lipolysis in man

Cited by 47 publications

References 27 publications

Lipolysis—Not inflammation, cell death, or lipogenesis—Is involved in adipose tissue loss in cancer cachexia

Lipolysis—Not inflammation, cell death, or lipogenesis—Is involved in adipose tissue loss in cancer cachexia

Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients

Computational modeling of cancer cachexia

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