Gluconeogenesis, liver energy metabolism and weight loss in lung cancer : dynamic studies using stable isotope tracers and 31P magnetic resonance spectroscopy

Weight loss is a major problem in many types of cancer and is associated with reduced quality of life and a poor prognosis. Weight loss can also interfere with potentially curable treatment [41,561. Many uncertainties remain about the mechanisms underlying weight loss in patients with cancer. This thesis describes a series of studies aimed at defining alterations in metabolic processes that are potentially related with weight loss in lung cancer patients. Although in literature the terms 'cachexia' (~ a syndrome of weight loss and rnalnutrition) and 'weight loss' are often used interchangeably, in this thesis weight loss will be preferentially used. In this chapter, current knowledge on weight loss in cancer and its relation with metabolic alterations are reviewed and the aim of this thesis is presented

Weight loss and elevated gluconeogenesis from alanine in lung cancer patients

BACKGROUND: The role of gluconeogenesis from protein in the pathogenesis of weight loss in lung cancer is unclear. OBJECTIVE: Our aim was to study gluconeogenesis from alanine in lung cancer patients and to analyze its relation to the degree of weight loss. DESIGN: In this cross-sectional study, we used primed-constant infusions of [6,6-(2)H(2)]-D-glucose and [3-(13)C]-L-alanine to assess whole-body glucose and alanine turnover and gluconeogenesis from alanine in weight-losing (WL, n = 9) and weight-stable (WS, n = 10) lung cancer patients and healthy control (n = 15) subjects. RESULTS: Energy intake and plasma alanine concentrations did not differ significantly among the subject groups. Mean (+/-SEM) whole-body glucose production was significantly higher in WL than in WS and control subjects (0.74 +/- 0.06 compared with 0.55 +/- 0.04 and 0.51 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Alanine turnover was significantly elevated in WL compared with WS and control subjects (0.57 +/- 0.04 compared with 0.42 +/- 0.05 and 0.40 +/- 0.03 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Gluconeogenesis from alanine was significantly higher in WL than in WS and control subjects (0.47 +/- 0.04 compared with 0.31 +/- 0.04 and 0.29 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). The degree of weight loss was positively correlated with glucose and alanine turnover and with gluconeogenesis from alanine (r = 0.45 for all, P < 0.01). CONCLUSIONS: Aberrant glucose and alanine metabolism occurred in WL lung cancer patients. These changes were related to the degree of weight loss and not to the presence of lung cancer per se