Reversed glucose and fatty acids transporter expression in human endometrial cancer.

Cancer cells exhibit accelerated rates of metabolism favoring glucose over fatty acid (FA) utilization. For both energy substrates, protein-mediated transport plays an essential role in facilitating glucose or FA movement across plasma membrane into the cells. Scarce data exist regarding the expression of glucose and/or FA transporter in cancer tissue. Therefore, we examined glucose (GLUT-1, GLUT-3, GLUT-4) and FA (FAT/CD36, FABPpm, FATP-1) transporter expressions at the protein and post-transcript (mRNA) levels in 35 endometrial carcinomas (G1, type endometrioid, FIGO I) and compared them with normal endometrial mucosa (n=10). Endometrial cancer tissue had significantly greater protein expression of GLUT-1, GLUT-3, and GLUT-4 (+ 40%; + 20%; + 24%; p<0.05, respectively) and, conversely, lower fatty acid (FAT/CD36 and FATP-1) transporter expression ( - 25%; p<0.05 and - 15%, p>0.05 respectively). Interestingly, mRNA content closely mirrors the changes, but only for glucose transporters and not fatty acid transporters. These results suggest the presence of metabolic switch of energy utilization in endometrial cancers favoring glucose consumption as the major source of energy.

Liver X receptor agonist T0901317 enhanced peroxisome proliferator-activated receptor-delta expression and fatty acid oxidation in rat skeletal muscle.

Liver X receptors (LXR) have been characterized as key transcriptional regulators of hepatic lipid and carbohydrate metabolism. LXR are expressed also in skeletal muscle, however, their role in this tissue is poorly investigated and the vast majority of available data comes from studies on cultured myotubes. Therefore, we aimed to examine effects of in vivo LXR activation on muscle lipid metabolism. The experiments were performed on male Wistar rats fed on a standard rodent chow. The animals were divided into two groups (n=10) receiving either LXR activator (T0901317, 10 mg/kg/day) or vehicle for one week. Samples of the soleus as well as red and white sections of the gastrocnemius muscle were excised. T0901317 increased muscle expression of peroxisome proliferator-activated receptor-δ and its target genes involved in fatty acid uptake and oxidation. In addition, LXR agonist enhanced palmitate oxidation (by 55%) in isolated soleus muscle. However, palmitate incorporation into triacylglycerol was decreased (by 38%), which was associated with reduced diacylglycerol acyltransferase expression (by 66%). Despite markedly increased plasma lipid concentration upon T0901317 treatment, muscle triacylglycerol level was elevated only in the red section of the gastrocnemius muscle. We conclude that T0901317 enhances muscle fatty acid oxidation, which prevents overt accumulation of intramuscular lipids that could be expected considering T0901317-induced hyperlipidemia.

LXR activation prevents exhaustive exercise-induced hypoglycaemia and spares muscle glycogen but does not enhance running endurance in untrained rats.

AIM: Liver X receptors (LXRs) are ligand-activated transcription factors that play an important role in regulation of hepatic lipid and carbohydrate metabolism. However, to date there is very few information on the role of LXRs in skeletal muscle. Moreover, it remains obscure whether LXR activation affects physical endurance. Therefore, we aimed to examine effects of selective LXR activator--T0901317--on running endurance and skeletal muscle exercise metabolism in rats. METHODS: The animals were assigned to two groups (n=20) receiving either vehicle or T0901317 (10 mg kg(-1) day(-1) ) for 1 week. One day after the final administration, half of the rats in each group were exercised until exhaustion on the electrically driven treadmill. All animals were then anaesthetized and samples of the soleus, red and white sections of the gastrocnemius muscle, epididymal fat pad and liver were excised. RESULTS: We found that LXR activation prevented exhaustive exercise-induced hypoglycaemia. T0901317 also shifted substrate utilization in working muscles in favour of fatty acids as indicated by its glycogen sparing effect, enhanced consumption of intramuscular triacylglycerol and upregulation of genes promoting fatty acid oxidation and suppressing carbohydrate oxidation. However, running time to exhaustion was not improved. CONCLUSION: We conclude that LXR activation increases fatty acid utilization during exercise which, however, does not translate into measurable enhancement of exercise endurance.