OBJECTIVE: Cachexia leads to weight loss and muscle wasting, reducing quality and length of life for advanced cancer patients. There is increasing interest in studying cachexia in the context of obesity due to its increasing worldwide prevalence. C57Bl6 mice are susceptible to diet-induced obesity and Lewis lung carcinoma (LLC)-induced cachexia; however, challenges with this model include large tumor sizes with ulcerations and a mild cachexia phenotype in females. Therefore, this study tested the effect of injecting fewer LLC cells compared to previous studies at either one or two sites in female mice on a Western diet. We hypothesized this would decrease tumor growth rate and ulcerations, enabling longer study duration and overt cachexia development. RESULTS: Contrary to our hypothesis, over half of tumors developed ulcerations, requiring study termination at 19 days. However, mice with one and two tumors still developed mild and severe cachexia, respectively. Total tumor mass was less predictive of cachexia severity than tumor number. These data show bilateral injections of 250,000 LLC cells induced significant cachexia in female mice on a Western diet, despite a shortened study timeline. These findings are important for improving pre-clinical modeling of cachexia in the context of Western-style obesogenic diets and obesity.
Rodriguez et al. (Tue,) studied this question.