Abstract
Cancer is commonly associated with cachexia, a paraneoplastic syndrome characterized by body weight loss, muscle wasting, adipose tissue atrophy and inflammation. Chronic alcohol consumption increases the risk of multiple types of cancer, and enhances cancer-associated cachexia (CAC), but the underlying mechanisms remain poorly defined. To test, C57BL/6 mice were fed with 0% or 20% (w/v) alcohol for 3 months, then inoculated with B16BL6 melanoma cells subcutaneously in the right side of the hip and continued to feed with/without alcohol for 3 or 4 weeks. Alcohol intake upregulated ALDH1A1 expression and elevated retinoic acid (RA) content in inguinal white adipose tissue (iWAT), which led to enhanced iWAT browning and brown adipose tissue (BAT) activation, accelerating fat loss. Moreover, alcohol increased muscle loss through augmenting muscle protein degradation, cell apoptosis and inflammation. In addition, alcohol reduced satellite cell density and impaired myogenesis in skeletal muscle. Taken together, alcohol aggravates cancer-associated cachexia at least partially through elevating adipose browning and muscle atrophy.
Highlights
Cancer-associated cachexia (CAC) is a paraneoplastic syndrome characterized by body weight loss, muscle wasting, adipose tissue atrophy and inflammation [1,2,3]
Due to the large variations in weight loss among mice inoculated with tumors, the weights of tibialis anterior muscle (TA), gastrocnemius muscle (GA) and vastus lateralis muscle (VA) between mice with/without alcohol did not reach significance (Figure 1E–1G)
We discovered that alcohol consumption aggravates cancer induced cachexia partially via inducing white adipose tissue browning
Summary
Cancer-associated cachexia (CAC) is a paraneoplastic syndrome characterized by body weight loss, muscle wasting, adipose tissue atrophy and inflammation [1,2,3]. Because cachectic patients have reduced food intake [6], nutritional supplementary therapy partially reverses the wasting associated with cachexia [5], but the effectiveness is limited, suggesting the existence of additional mechanisms besides nutrition which are responsible for CAC incidence. Brown adipose tissue (BAT) activation [9,10,11] and beige adipocyte formation [3, 12] in cancer patients and tumorbearing animal models increase energy consumption, which precedes adipose tissue and skeletal muscle atrophy [3]
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