Alcoholic myopathy: biochemical mechanisms.
Between one- and two-thirds of all alcohol abusers have impairment of muscle function that may be accompanied by biochemical lesions and/or the presence of a defined myopathy characterised by selective atrophy of Type II fibres. Perturbations in protein metabolism are central to the effects on muscle and account for the reductions in muscle mass and fibre diameter. Ethanol abuse is also associated with abnormalities in carbohydrate (as well as lipid) metabolism in skeletal muscle. Ethanol-mediated insulin resistance is allied with the inhibitory effects of ethanol on insulin-stimulated carbohydrate metabolism. It acutely impairs insulin-stimulated glucose and lipid metabolism, although it is not known whether it has an analogous effect on insulin-stimulated protein synthesis. In alcoholic cirrhosis, insulin resistance occurs with respect to carbohydrate metabolism, although the actions of insulin to suppress protein degradation and stimulate amino acid uptake are unimpaired. In acute alcohol-dosing studies defective rates of protein synthesis occur, particularly in Type II fibre-predominant muscles. The relative amounts of mRNA-encoding contractile proteins do not appear to be adversely affected by chronic alcohol feeding, although subtle changes in muscle protein isoforms may occur. There are also rapid and sustained reductions in total (largely ribosomal) RNA in chronic studies. Loss of RNA appears to be related to increases in the activities of specific muscle RNases in these 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 total RNA. These data implicate a role for translational modifications in the initial stages of the myopathy, although changes in transcription and/or protein degradation may also be superimposed. These events have important implications for whole-body metabolism.
Preedy
V R
VR
Department of Nutrition and Dietetics, King's College London, 150 Stamford Street, SE1 9NN, London, UK.
Paice
A
A
Mantle
D
D
Dhillon
A S
AS
Palmer
T N
TN
Peters
T J
TJ
D000437:Alcoholism / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism*
D009124:Muscle Proteins; D000431:Ethanol