While chemotherapy remains a common cancer treatment, it is associated with debilitating side effects (e.g., anorexia, weight loss, and fatigue) that adversely affect patient quality of life and increase mortality. However, the mechanisms underlying taxane chemotherapy-induced side effects, and effective treatments to ameliorate them, are not well-established. Here, we tested the longitudinal relationship between a clinically-relevant paclitaxel regimen, inflammation, and sickness behaviors (loss of body mass, anorexia, fever, and fatigue) in adult, female mice. Furthermore, we sought to identify the extent to which voluntary exercise (wheel running) attenuates paclitaxel-induced sickness behaviors and underlying central pathways. Body mass and food intake decreased following six doses of chemotherapy treatment relative to vehicle controls, lasting less than 5 days after the last dose. Paclitaxel treatment also transiently decreased locomotion (open field test), voluntary wheel running, home-cage locomotion, and core body temperature without affecting motor coordination (rotarod task). Circulating interleukin (IL)-6 and hypothalamic Il1b gene expression remained elevated in chemotherapy-treated mice at least 3 days after the last dose. Exercise intervention did not ameliorate fatigue or inflammation, but hastened recovery from paclitaxel-induced weight loss. Body mass recovery was associated with the wheel running-induced recovery of body composition, paclitaxel-induced alterations to hypothalamic melanocortin signaling, and associated peripheral circulating hormones (ghrelin and leptin). The present findings demonstrate the benefits of exercise on faster recovery from paclitaxel-induced body mass loss and deficits in melanocortin signaling and suggests the development of therapies targeting the melanocortin pathway to reduce paclitaxel-induced weight loss.

虽然化疗仍然是一种常见的癌症治疗方法，但它会产生使人衰弱的副作用（例如厌食、体重减轻和疲劳），从而对患者的生活质量产生不利影响并增加死亡率。然而，紫杉烷化疗引起的副作用的机制以及改善这些副作用的有效治疗方法尚未明确。在这里，我们在成年雌性小鼠中测试了临床相关紫杉醇治疗方案、炎症和疾病行为（体重减轻、厌食、发烧和疲劳）之间的纵向关系。此外，我们试图确定自愿运动（跑轮）在多大程度上减轻紫杉醇引起的疾病行为和潜在的中枢通路。相对于赋形剂对照组，经过六剂化疗治疗后，体重和食物摄入量有所下降，并在最后一次给药后持续不到 5 天。紫杉醇治疗还暂时降低运动（旷场测试）、自愿轮跑、家笼运动和核心体温，而不影响运动协调性（旋转任务）。在接受化疗的小鼠中，在最后一次给药后至少 3 天，循环白细胞介素 (IL)-6 和下丘脑Il1b基因表达仍然升高。运动干预并不能改善疲劳或炎症，但可以加速紫杉醇引起的体重减轻的恢复。体重恢复与车轮行驶引起的身体成分恢复、紫杉醇引起的下丘脑黑皮质素信号改变以及相关的外周循环激素（生长素释放肽和瘦素）相关。 目前的研究结果表明，运动有助于从紫杉醇引起的体重减轻和黑皮质素信号传导缺陷中更快恢复，并建议开发针对黑皮质素途径的疗法以减少紫杉醇引起的体重减轻。