Exercise Training Reduces PGE₂Levels and Induces Recovery from Steatosis in Tumor-bearing Rats

Abstract

The effects of endurance training on PGE (2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO (2) max) for 60 min/day, 5 days/week, for 8 weeks. We examined the mRNA expression (RT-PCR) and maximal activity (radioassay) of the carnitine palmitoyltransferase system enzymes (CPT I and CPT II), as well as the gene expression of fatty-acid-binding protein (L-FABP) in the liver. PGE (2) content was measured in the serum, in tumor cells, and in the liver (ELISA). CPT I and CPT II maximal activity were decreased (p<0.01) in ST when compared with SC. In contrast, serum PGE (2) was increased (p<0.05) in cachectic animals as compared with SC. In the liver, PGE (2) content was also increased (p<0.05) when compared with SC. Endurance training restored maximal CPT I and CPT II activity in the tumor-bearing animals (p<0.0001). Exercise training induced PGE (2) levels to return to control values in the liver of tumor-bearing training rats (p<0.05) and decreased the eicosanoid content in the tumor (p<0.01). In conclusion, endurance training was capable of reestablishing liver carnitine palmitoyltransferase (CPT) system activity associated with decreased PGE (2) levels in cachectic tumor-bearing animals, preventing steatosis.

Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats

“…Corroborating our suggestion, PGE2 decreased CPT1 expression in isolated hepatocytes and the PGE2-dependent repression of CPT1 resulted in inhibition of mitochondrial β-oxidation and triacylglycerol accumulation in hepatocytes [35]. In addition, the exercise training normalized the increased level of PGE2 in the liver of Walker-256 tumor-bearing rats, restored the decreased activity of CPT1 and CPT2 and prevented hepatic steatosis [34]. Moreover, treatment with PGE2 or PGE2 receptor agonist increased the triacylglycerol in the liver [36].…”

“…5B) and the decreased CPT1 expression in the liver of tumor-bearing rats (Fig. 6), suggesting a role of PGE2, which is increased in the liver [34] and blood [15,34] of Walker-256 tumor-bearing rats, in the inhibition of CPT1. Corroborating our suggestion, PGE2 decreased CPT1 expression in isolated hepatocytes and the PGE2-dependent repression of CPT1 resulted in inhibition of mitochondrial β-oxidation and triacylglycerol accumulation in hepatocytes [35].…”

“…Thereby, the lower ATP level in the liver of tumor-bearing rats could be due to reduction in mitochondrial β-oxidation of fatty acids. Really, it was shown that the hepatic capacity of fatty acids oxidation is decreased in Walker-256 tumor-bearing rats [3], a phenomena that seem to be caused by reduction of CPT1 and CPT2 activity, enzymes involved in the transport of fatty acids from cytosol to mitochondria [3,5,34].…”

l-Carnitine induces recovery of liver lipid metabolism in cancer cachexia

“…In addition, L-carnitine supplementation may protect hepatocytes of tumour-bearing rats from oxidative damage, since free fatty acids are able to produce damage on cell and mitochondrial surfaces (Bremer 1981). In addition, we have recently published a study in which we show that increased CPT activity is found in association with reduction in the enhancement in liver prostaglandin E2 content which is related with cachexia (Lira et al 2010). Roy et al (2009) found decreased PGE2 production by Caco-2 cells following treatment with carnitine.…”

Methodological issues when analysing the role of physical activity in gastric cancer prevention: a critical review

“…Thus, exercise could reduce the inflammation of the stomach of epithelium, as it has been previously proposed in other chronic inflammatory digestive disorders [2]. In the same line, the concentration of prostaglandin E 2 , a marker of inflammation that has been associated with gastric cancer risk [17], could be reduced due to the performance of endurance exercise [34]. Regarding the systemic effects, the evidence is based on the influence that the exercise performance seems to have on the immune system, mainly by improving its innate and acquired immune responses when recognising and eliminating cancerous cells [24].…”