Effect of Tumor Burden on Futile Glucose and Lipid Cycling in Tumor-Bearing Animals

Futile cycling of metabolic substrates may play an important role in the development of cancer cachexia. To determine the effect of tumor burden on futile glucose and lipid cycling, 64 female Lewis/Wistar rats were randomized to control (non-tumor-bearing), small tumor burden, or large tumor burden groups (MAC-33 mammary adenocarcinoma). After 5 or 25 days of tumor growth, animals received a 5-day period of parenteral nutrition (158 kcal/kg/day) followed by a 6-hr infusion of the stable isotopes glucose-2-d and glucose-6,6-d2 or [C13]palmitate. The heavy glucose isotopes glucose-2-d and glucose-6,6-d2 are labeled with deuterium at the 2-carbon position and doubly labeled with deuterium at the (6-carbon position, respectively, to obtain differential molecular weights. No increase in glucose or lipid cycling was observed in animals with small tumor burdens. In contrast, a significant increase in plasma rate of appearance (Ra) of glucose-2-d (1377 ± 136 mg/hr vs 947 ± 54 mg/hr), Ra of glucose-6,6-d2 (810 ± 88 mg/hr vs 510 ± 24 mg/hr), and total glucose cycling (548 ± 57 mg/hr vs 416 ± 28 mg/hr) was seen in animals with large tumor burdens compared to control animals (P < 0.05). Although a trend toward increased lipid cycling was seen in tumor-bearing versus control animals, this change was not significant. Thus, futile cycling of glucose was significantly elevated in animals with large tumor burdens and may cause significant energy wasting to contribute to the development of cachexia in the tumor-bearing host.