Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia

Objective: Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Methods: Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Results: Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P <0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Conclusions: Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function.