Alcohol intake aggravates adipose browning and muscle atrophy in cancer-associated cachexia
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Bo Wang1,2,*, Faya Zhang3,*, Hui Zhang3, Zhixiu Wang2, Yan-Nan Ma2,5, Mei-Jun Zhu3 and Min Du1,2
1Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing 100094, P. R. China
2Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA
3Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99210, USA
4School of Food Science, Washington State University, Pullman, WA 99164, USA
5Department of Chemistry and Lifer Sciences, Gansu Normal University for Nationalities, Hezuo 747000, P. R. China
*These authors have contributed equally to this work
Min Du, email: email@example.com
Hui Zhang, email: firstname.lastname@example.org
Keywords: alcohol; cachexia; adipose browning; muscle atrophy; retinoic acid
Received: August 24, 2017 Accepted: October 13, 2017 Published: November 01, 2017
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.
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