Substrate alterations in a sarcoma-bearing rat model: Effect of tumor growth and resection

Abstract

The time course of plasma substrate level alterations in the tumor-bearing (TB) host and their relationship to tumor burden or weight loss has not been well defined. Plasma glucose, lactate, pyruvate, cholesterol, triglycerides, acetoacetate, β-hydroxy butyrate, and glycerol levels were measured in postabsorptive TB and nontumor-bearing (NTB) male Fisher 344 rats at weekly intervals for 5 weeks. Chronically starved rats (CS) had plasma substrates measured at Week 3 and compared with TB and NTB levels. Tumor burden was 0.5% of body weight at Week 1, 3.5% at Week 2, 12% at Week 3, and 20% at Week 5. Glucose levels were significantly lower in TB versus NTB ( P = 0.01) at Week 1 and progressively declined in TB versus NTB through Week 5 ( P < 0.001). At Week 2, plasma triglycerides, cholesterol, acetoacetate, and β-hydroxy butyrate were significantly elevated in TB versus NTB ( P < 0.001) and increased further to Week 5. The profile of substrate changes in TB and CS, when compared to NTB rats at Week 3, were different, suggesting that the plasma substrate alterations seen in the TB state were not secondary to starvation. In addition, when tumors were excised from TB animals at Week 3 and plasma substrates were determined 1 week later, all substrates that were different between TB and NTB animals, except cholesterol, returned to NTB levels when compared to sham-operated controls. Significant changes in plasma substrate levels occur in the TB host prior to the onset of weight loss or cachexia and appear related to the degree of tumor burden. Furthermore, these substrate alterations are reversible with extirpation of the tumor and appear metabolically distinct from chronic starvation.