Loss of adipose tissue and plasma phospholipids: Relationship to survival in advanced cancer patients

Murphy, Rachel A.; Wilke, Michaelann S.; Perrine, Michael; Pawłowicz, Monika; Mourtzakis, Marina; Lieffers, Jessica; Maneshgar, M.; Bruera, Éduardo; Clandinin, Michael T.; Baracos, Vickie E.; Mazurak, Vera C.

doi:10.1016/j.clnu.2009.11.006

Cited by 122 publications

(125 citation statements)

References 25 publications

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“…Changes in triglyceride levels in plasma have been associated with cancers (Ma et al 2011, Fiorenza et al 2000, Ulmer et al 2009). Previous studies have noted a decrease in plasma phospholipids and lysophospholipids in advanced cancer, attributed to a loss of essential fatty acids in the periphery (Murphy et al 2012(Murphy et al , 2010. Hence our observations are consistent with previous studies.…”

Section: Discussionsupporting

confidence: 83%

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

Ravipati

Baldwin²,

Barr

et al. 2015

Metabolomics

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There is a clinical need for reliable biomarkers for lung cancer that permit early diagnosis of the disease and provide prediction of histological phenotype. A prospective study design was used with a study population of patients with suspected lung cancer. Blood samples were collected from 17 patients with histologically confirmed squamous cell lung carcinoma, 17 individuals with adenocarcinoma, and 17 control individuals who did not subsequently have a diagnosis of lung cancer or any other cancer. Blood plasma samples were analysed for their lipid profiles using liquid chromatography coupled with high resolution mass spectrometry. Data were analysed using multivariate statistical methods. There was good separation between histological subtypes and control groups and also between individuals with a subsequent diagnosis of adenocarcinoma and squamous cell carcinoma (sensitivity 80%, specificity 83%, Q 2 =0.70). Alterations in the levels of different classes of lipids including triglycerides (TGs), phosphatidylinositols (PIs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), free fatty acids, lysophospholipids and sphingolipids were observed in squamous carcinoma and adenocarcinoma lung cancer patients when compared with control patients. In conclusion, this study has identified candidate lipid biomarkers of non-small cell lung cancer patients which may be helpful to indicate the tumour subtype and to differentiate them from patients who do not have lung cancer. Measuring these biomarkers has the potential to improve diagnosis in patients with suspected lung cancer and risk stratification in screening.

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Section: Discussionsupporting

confidence: 83%

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

Ravipati

Baldwin²,

Barr

et al. 2015

Metabolomics

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“…6,[11][12][13][14]37,38 Mechanistic studies suggest PKA-induced lipolysis is not enhanced in late stage cachexia; 38 instead, increased expression of lipases may be responsible for lipid catabolism in adipose tissue in these more advanced stages of cachexia. 13,38 Studies have also reported enhanced lipid accumulation in muscle in cachectic patients with increased weight loss 29,39 and hepatic steatosis in fully-established cachexia in experimental tumor-bearing animals.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Fat loss, however, may precede muscle wasting in cachexia 5 and several recent longitudinal studies in cancer patients found accelerated loss of adipose tissue predicted poorer survival. [6][7][8] Moreover, in 2 different murine models of cancer cachexia, preserving fat mass by genetically inhibiting lipolysis also preserved skeletal muscle mass. 9 Thus, unveiling the mechanisms of adipose tissue depletion may contribute to the development of therapies that improve both survival and qualityof-life outcomes in cachectic patients.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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“…In addition, higher plasma phospholipid EPA and DHA concentrations, as observed in the FO group, have been shown to be predictive of increased survival in patients with advanced cancer. 34 A further study by Gogos et al 35 demonstrated increased survival in patients with generalized malignancy when provided with fish oil versus placebo. Although we were unable to calculate overall survival because of the large number of censored patients, we continue to follow the study patients to determine the effect of FO on overall survival.…”

Section: Discussionmentioning

confidence: 99%

Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer

Murphy

Mourtzakis

Chu

et al. 2011

Cancer

194

106

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Loss of adipose tissue and plasma phospholipids: Relationship to survival in advanced cancer patients

Cited by 122 publications

References 25 publications

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

Plasma lipid biomarker signatures in squamous carcinoma and adenocarcinoma lung cancer patients

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer

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