Decreased energy and phosphorylation status in the liver of lung cancer patients with weight loss

Background/Aims: Altered energy status has been reported in the liver of tumour-bearing animals, but data on energy status in humans are scarce. Therefore, bioenergetics in tumour-free liver of lung cancer patients were monitored using 31P magnetic resonance spectroscopy (MRS) with infusion of L-alanine as a gluconeogenic challenge. Methods: Twenty-one overnight-fasted lung cancer patients without liver metastases, with (CaWL) or without weight loss (CaWS), and 12 healthy control subjects (C) were studied. Hepatic energy status was monitored before and during an i.v. L-alanine infusion of 1.4–2.8 mmol/kg + 2.8 mmol • kg−1 • h−1 for 90 min by 31P MR spectroscopy. Results: Baseline levels of ATP in WL lung cancer patients, expressed relative to total MR-detectable phosphate, were reduced (CaWL, 9.5±0.9% vs. CaWS, 12.6±0.8% and C, 12.4±0.8%; p<0.05) and inversely correlated with the degree of weight loss in lung cancer patients (r=−0.46, p=0.03). Pi/ATP ratios were increased (p<0.05), indicating reduced liver phosphorylation status. During L-alanine infusion, ATP levels decreased in all groups (p<0.05); in CaWL, ATP levels were lower at all time-points between 0–90 min as compared to both CaWS and C (p<0.05). Pi/ATP ratios were significantly higher after 70–90 min of L-alanine infusion in CaWL compared to CaWS and C (p<0.05). Conclusions: Hepatic ATP and phosphorylation status are reduced in WL lung cancer patients, in contrast to WS patients and healthy subjects, and continue to decrease during infusion of a gluconeogenic substrate, suggesting impaired energy regenerating capacity in these patients.