The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.
Keywords: Adipose tissue; Body wasting; Chemotherapy; Lipolysis; Thermogenesis.
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