Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in white adipose tissue

Beck, S. A.; Tisdale, Michael J.

doi:10.1007/s11745-004-1346-8

Cited by 31 publications

(24 citation statements)

References 5 publications

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“…Cancer cachexia is characterized by the uncontrolled loss of adipose and muscle mass (27). Compared with non-tumor-bearing animals, the rate of triglyceride production increased almost threefold in animals bearing the MAC13 tumor (28). In our study, the PKRI, MPA, and PKRI+MPA groups had a significantly lower level of triglyceride than the placebo group.…”

Section: Discussionsupporting

confidence: 41%

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

Chen

Zhang²

2011

Oncol Rep

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Abstract. Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare these two drugs, alone or in combination, in cancer cachexia in mice. Forty male BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo, and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma and fed for 12 days and then treated with PKRI and MPA alone or in combination for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were measured. The tumor growth (volume and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that of placebo group. Wet weight of gastrocnemius muscle was significantly higher in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing mice had a significantly lower level of blood glucose, higher level of serum triglyceride and lower level of serum albumin compared with healthy control (P<0.001). However, PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose and lower level of serum triglyceride compared with placebo group (P<0.001). All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 and IL-6 compared with healthy control (P<0.001). Serum level of TNF-α and IL-6 was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may alleviate cachexia.

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Section: Discussionsupporting

confidence: 41%

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

Chen

Zhang²

2011

Oncol Rep

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“…There have been few measurements of this cycle in cancer patients or animal tumor models. In one of the few studies in murine tumor-bearing animals, the rate of TAG/FA cycling was increased over that found in nontumor-bearing animals, irrespective of the development of cachexia (16). However, cachectic animals did show an elevated de novo synthesis of TAG/FA.…”

Section: Role Of Futile Cyclesmentioning

confidence: 88%

Mechanisms of Cancer Cachexia

Tisdale

2009

Physiological Reviews

994

1,061

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Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the α-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NFκB. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-α, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment.

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“…22 Stimulation of lipolysis alone would not deplete body fat stores, as without an energy sink, the liberated NEFA would be resynthesized back into triglycerides in adipocytes. 23 To reduce body fat, ZAG not only increases lipolysis, as shown by an increase in plasma glycerol, but also increases the lipid utilization, as shown by the decrease in plasma levels of triglycerides and NEFA. This energy is channelled into heat, as evidenced by the 0.4 1C rise in body temperature in rats treated with ZAG.…”

Section: Discussionmentioning

confidence: 99%

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

Russell

Tisdale

2010

Int J Obes

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Objective: To investigate the anti-obesity effect of the adipokine zinc-a 2 -glycoprotein (ZAG) in rats and the mechanism of this effect. Subjects: Mature male Wistar rats (540±83 g) were administered human recombinant ZAG (50 mg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). Results: Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 1C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. Conclusion: These results show that ZAG produces increased lipid mobilization and utilization in the rat.

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Effect of cancer cachexia on triacylglycerol/fatty acid substrate cycling in white adipose tissue

Cited by 31 publications

References 5 publications

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate

Mechanisms of Cancer Cachexia

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

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