Alcoholic myopathy: biochemical mechanisms

Between one- and two-thirds of all alcohol abusers have impairment of muscl e function that may be accompanied by biochemical lesions and/or the presen ce of a defined myopathy characterised by selective atrophy of Type II fibr es. Perturbations in protein metabolism are central to the effects on muscl e and account for the reductions in muscle mass and fibre diameter. Ethanol abuse is also associated with abnormalities in carbohydrate las well as li pid) metabolism in skeletal muscle. Ethanol-mediated insulin resistance is allied with the inhibitory effects of ethanol on insulin-stimulated carbohy drate metabolism. It acutely impairs insulin-stimulated glucose and lipid m etabolism, although it is not known whether it has an analogous effect on i nsulin-stimulated protein synthesis. In alcoholic cirrhosis, insulin resist ance occurs with respect to carbohydrate metabolism, although the actions o f insulin to suppress protein degradation and stimulate amino acid uptake a re unimpaired. In acute alcohol-dosing studies defective rates of protein s ynthesis occur, particularly in Type II fibre-predominant muscles. The rela tive amounts of mRNA-encoding contractile proteins do not appear to be adve rsely affected by chronic alcohol feeding, although subtle changes in muscl e protein isoforms may occur. There are also rapid and sustained reductions in total (largely ribosomal) RNA in chronic studies. Loss of RNA appears t o be related to increases in the activities of specific muscle RNases in th ese long-term studies. However, in acute dosing studies (less than 1 day), the reductions in muscle protein synthesis are not due to overt loss of tot al RNA. These data implicate a role for translational modifications in the initial stages of the myopathy, although changes in transcription and/or pr otein degradation may also be superimposed. These events have important imp lications for whole-body metabolism. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.