Lipid metabolism in cancer cachexia

Mulligan, H. D.; Beck, S. A.; Tisdale, M. J.

doi:10.1038/bjc.1992.216

Cited by 25 publications

(16 citation statements)

References 15 publications

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“…34 Thus, cachectic mice bearing the MAC16 tumour showed an increased rate of release of [U- 14 C] palmitate from epididymal fat pads than either non-tumour-bearing mice or mice bearing the MAC13 tumour, which does not induce cachexia. 21 Using the same technique, this study shows an enhanced rate of loss of radioactivity from [U-…”

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confidence: 87%

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

Russell

Tisdale

2010

Int J Obes

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Objective: To investigate the mechanism of the lipid depletion by zinc-a 2 -glycoprotein (ZAG). Design: Studies were conducted in the ob/ob mouse, or on isolated adipocytes from these animals or their lean counterparts. Results: Treatment of these animals for 15 days with ZAG (100 mg, intravenously, daily) resulted in a reduction of body weight of 6.55 g compared with phosphate-buffered saline-treated controls, without a change in food or water intake, but with a 0.4 1C rise in rectal temperature. ZAG-treated mice had a 30% reduction in carcass fat mass and a twofold increase in weight of brown adipose tissue. Epididymal adipocytes from ZAG-treated mice showed an increased expression of ZAG and hormone-sensitive lipase (HSL), and this was maintained for a further 3 days in the absence of ZAG. There was an increased lipolytic response to isoproterenol, which was retained for 3 days in vitro in the absence of ZAG. Expression of HSL was also increased in subcutaneous and visceral adipose tissue, as was also adipose triglyceride lipase (ATGL). There was a rapid loss of labelled lipid from epididymal adipose tissue of ZAG-treated mice, but not from the other depots, reflecting the difference in sensitivity to lipolytic stimuli. The increased expression of HSL and ATGL may involve the extracellular signal-regulated kinase (ERK) pathway, as the active (phospho) form was upregulated in all adipose depots after ZAG administration, whereas in vitro studies showed induction of HSL and ATGL by ZAG to be attenuated by PD98059, an inhibitor of the ERK pathway. Conclusion: These results suggest that ZAG not only induces direct lipolysis, but also sensitizes adipose tissue to other lipolytic stimuli.

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confidence: 87%

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

Russell

Tisdale

2010

Int J Obes

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“…114 Levels of mRNA for HSL were elevated twofold in adipose tissue of cancer patients. 114,241,242 Hyltander and colleagues 243 believe that increases in both ␤(1) and ␤(2)-adrenoceptor activity are involved in increasing resting energy metabolism. Gambardella et al 244 showed that propranolol can reduce the basal metabolic rate of cancer patients, and Khan and Tisdale 116 found that ␤-blockers can also attenuate LMF-induced lipolysis in vitro.…”

Section: Fatty Tissue Oxidationmentioning

confidence: 97%

The Cytokine Basis of Cachexia and its Treatment: Are They Ready for Prime Time?

Yeh

Blackwood

Schuster

2008

Journal of the American Medical Directors Association

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“…14 C] triolein (Mulligan et al, 1992b) indicative of an increase in lipid utilisation. Hypoglycaemia induced by LMF arises from an increased glucose consumption by the brain, heart, BAT and gastrocnemius muscle.…”

Section: Discussionmentioning

confidence: 99%

Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo

Russell

Tisdale

2002

Br J Cancer

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Treatment of ex-breeder male NMRI mice with lipid mobilising factor isolated from the urine of cachectic cancer patients, caused a significant increase in glucose oxidation to CO 2, compared with control mice receiving phosphate buffered saline. Glucose utilisation by various tissues was determined by the 2-deoxyglucose tracer technique and shown to be elevated in brain, heart, brown adipose tissue and gastrocnemius muscle. The tissue glucose metabolic rate was increased almost threefold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels. Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of Loss of whole body fat is a prominent feature of cancer cachexia, with losses of up to 85% being reported (Fearon, 1992) in lung cancer patients, who had lost 30% of their pre-illness stable weight. Most studies suggest that loss of fat arises as a result of an increased lipolysis, together with increased whole body fatty acid oxidation. Thus increased plasma concentrations of glycerol, free fatty acids (FFA) and triglycerides were observed in a heterogeneous group of cancer patients with an average loss of 13% of their original body weight (Legaspi et al, 1987). Basal fatty acid turnover was elevated by 25% above that for controls, and was found to be similar to the rate observed for patients with severe burns. Lipolysis was increased by 40% in patients in whom complete triglyceride hydrolysis without re-esterification was observed, and there was a 20% increase in fatty acid oxidation.Upregulation of catabolism, rather than defects in anabolism, appear to be most important in the loss of lipid from human adipose tissue in cancer cachexia. Thus Thompson et al (1993) have shown a two-fold increase in the relative level of mRNA for triglyceride lipase, while the relative levels of mRNA for lipoprotein lipase (LPL) and fatty acid synthase were not significantly different between cancer patients and controls. This suggests that cytokines such as tumour necrosis factor-a (TNF-a), interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-g (IFN-g) and leukaemiainhibitory factor (LIF), which have been proposed to decrease adipose tissue mass by decreasing synthesis of triglycerides through inhibition of LPL (Berg et al, 1994) probably play a minor role in the loss of lipid from human adipose tissue. It therefore seems more likely that lipid mobilisation in cancer cachexia can be attributed to tumour catabolic factors, such as lipid mobilising factor (LMF), which acts directly on adipose tissue with the release of FFA and glycerol in a manner similar to that of lipolytic hormones (Beck and Tisdale, 1987). LMF has been purified from the urine of patients with cancer cachexia using a combination of ion exchange, exclusion and hydrophobic interaction chromatographies (Todorov et al, 1998). Unlike polypeptide hormones stimulating lipolysis which are basic, LMF is acidic and showed homology in amino acid sequence, electrophoretic mobility and immunore...

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Lipid metabolism in cancer cachexia

Cited by 25 publications

References 15 publications

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

Studies on the antiobesity effect of zinc-α2-glycoprotein in the ob/ob mouse

The Cytokine Basis of Cachexia and its Treatment: Are They Ready for Prime Time?

Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo

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