Departments of Cellular & Molecular Physiology and Medicine (Endocrinology), Yale University School of Medicine, New Haven, Connecticut, United States.
Am J Physiol Endocrinol Metab. 2024 Mar 1;326(3):E290-E307. doi: 10.1152/ajpendo.00378.2023. Epub 2024 Jan 31.
Cancer-related fatigue (CRF) is one of the most prevalent and detrimental complications of cancer. Emerging evidence suggests that obesity and insulin resistance are associated with CRF occurrence and severity in cancer patients and survivors. In this narrative review, we analyzed recent studies including both preclinical and clinical research on the relationship between obesity and/or insulin resistance and CRF. We also describe potential mechanisms for these relationships, though with the caveat that because the mechanisms underlying CRF are incompletely understood, the mechanisms mediating the association between obesity/insulin resistance and CRF are similarly incompletely delineated. The data suggest that, in addition to their effects to worsen CRF by directly promoting tumor growth and metastasis, obesity and insulin resistance may also contribute to CRF by inducing chronic inflammation, neuroendocrinological disturbance, and metabolic alterations. Furthermore, studies suggest that patients with obesity and insulin resistance experience more cancer-induced pain and are at more risk of emotional and behavioral disruptions correlated with CRF. However, other studies implied a potentially paradoxical impact of obesity and insulin resistance to reduce CRF symptoms. Despite the need for further investigation utilizing interventions to directly elucidate the mechanisms of cancer-related fatigue, current evidence demonstrates a correlation between obesity and/or insulin resistance and CRF, and suggests potential therapeutics for CRF by targeting obesity and/or obesity-related mediators.
癌症相关性疲劳（CRF）是癌症最常见和最具危害性的并发症之一。新出现的证据表明，肥胖和胰岛素抵抗与癌症患者和幸存者的 CRF 发生和严重程度有关。在这篇叙述性综述中，我们分析了最近的研究，包括肥胖和/或胰岛素抵抗与 CRF 之间关系的临床前和临床研究。我们还描述了这些关系的潜在机制，但需要注意的是，由于 CRF 的机制尚未完全阐明，肥胖/胰岛素抵抗与 CRF 之间关联的介导机制也同样尚未完全描述。数据表明，肥胖和胰岛素抵抗除了通过直接促进肿瘤生长和转移来加重 CRF 外，还可能通过诱导慢性炎症、神经内分泌紊乱和代谢改变来导致 CRF。此外，研究表明，肥胖和胰岛素抵抗的患者会经历更多的癌症引起的疼痛，并且更有可能出现与 CRF 相关的情绪和行为障碍。然而，其他研究表明肥胖和胰岛素抵抗可能会降低 CRF 症状，这似乎存在矛盾。尽管需要进一步研究利用干预措施来直接阐明癌症相关性疲劳的机制，但目前的证据表明肥胖和/或胰岛素抵抗与 CRF 之间存在相关性，并提示通过针对肥胖和/或肥胖相关介质来治疗 CRF 的潜在疗法。
