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Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle
Author(s) -
Shenkman Boris S.,
Belova Svetlana P.,
Zinovyeva Olga E.,
Samkhaeva Nudlya D.,
Mirzoev Timur M.,
Vilchinskaya Natalia A.,
Altaeva Erzhena G.,
Turtikova Olga V.,
Kostrominova Tatiana Y.,
Nemirovskaya Tatiana L.
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13531
Subject(s) - anabolism , catabolism , endocrinology , medicine , myopathy , skeletal muscle , muscle atrophy , atrophy , metabolism
Background Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross‐sectional area ( CSA ) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Methods Skeletal muscle samples from 7 male patients with chronic alcohol abuse ( AL ; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA , and for the alterations in anabolic and catabolic signaling pathways. Results AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF ‐1 in plasma and IRS ‐1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK 3 β , and p90 RSK 1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP 70 and HSP 90. A marker of anabolic pathway p‐4E‐ BP 1 was decreased, while catabolic markers (Mu RF ‐1, MAF bx, ubiquitinated proteins) were increased in AL patients when compared with C group. Conclusions At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.