Elsevier

Journal of Hepatology

Volume 32, Issue 6, June 2000, Pages 887-892
Journal of Hepatology

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

https://doi.org/10.1016/S0168-8278(00)80092-6Get rights and content

Abstract

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.

Section snippets

Subjects

The study was approved by the Medical Ethical Committee of the Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands. Patients with non-small cell lung cancer stage IIIA/B or IV (WHO grading system) attending the outpatient department of the University Hospital Rotterdam, The Netherlands, were recruited. Patients who were in remission or apparently cured were excluded. Additional exclusion criteria were: liver metastases (as checked for by CT/ultrasound); metabolic disease;

Results

Fasting blood glucose levels were similar in lung cancer patients and did not change during L-alanine infusion. Baseline plasma alanine concentrations were similar between lung cancer patients and healthy controls (0.35–0.37 mM) and increased significantly during L-alanine infusion to 5.4±0.1 mM in CaWL, 6.7±0.5 mM in CaWS, and 8.5±0.9 mM in C (change from baseline and difference between all groups: p<0.001).

Discussion

In the present study, bioenergetics in the tumour-free liver of lung cancer patients during an i.v. L-alanine challenge were monitored using 31P MR spectroscopy. Alanine infusion is known to stimulate gluconeogenesis 21., 22., 23., and a standardised dose can be used to investigate gluconeogenic and energy metabolism within the liver by 31P MRS directly and non-invasively (24). In the present study, primed-constant infusion of 1.4–2.8 mmol · kg−1 L-alanine + 2.8 mmol · kg−1 · h−1 induced a

Acknowledgements

We are grateful to C. H. K. Hordijk-Luijk for performing biochemical analyses, and H. J. Agteresch, C. C. M. Bartels, M. Heijsteeg, F. Lagerwaard, A. S. T. Planting, M. J. M. van Mierlo, S. Senan, R. Slingerland, G. Stoter, M. M. A. Tilanus-Linthorst, J. Verweij, and A. G. Zwanenburg for their co-operation in the patient recruitment. We are grateful to W. Schneijderberg and C. Onna for their assistance during the experiments.

This project was supported by a grant from the Dutch Cancer Society

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