The total body mass of fatty acid ethyl esters in skeletal muscles following ethanol exposure greatly exceeds that found in the liver and the heart.
OBJECTIVE
Skeletal muscle appears to be susceptible to chronic and acute excess alcohol intake, giving rise to alcoholic myopathy, a common disease among alcoholics. Fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol, have been shown to be toxic to cells in vitro and in vivo. We hypothesized that accumulation of FAEE in skeletal muscle could contribute to the development of alcoholic myopathy.


METHODS
Male wistar rats were treated either with 75 mmol ethanol/kg body weight or saline, in the fed state or starved for 1 or 2 days before administration. Rats were thus divided into the following groups: fed-saline (n = 8); fed-ethanol (n = 8); starved 1 day, saline (n = 8); starved 1 day, ethanol (n = 9); starved 2 days, saline (n = 7); and starved 2 days, ethanol (n = 8). At the end of the incubation, skeletal muscles (abdominal and gastrocnemius), liver, and heart were isolated and processed for FAEE isolation and analysis by gas chromatography-mass spectrometry (GC-MS).


RESULTS
Total mass of FAEE in the muscles was much greater than that found in the liver and the heart. In general, the animals that were fasted for 1 day and received ethanol had the highest FAEE levels among the three groups of animals. The major ethyl ester species in all cases were ethyl 16:0, ethyl 18:0, ethyl 18:1 n-9, and ethyl 18:2 n-6. Ethyl 20:4 n-6 and ethyl 22:6 n-3 were also present, except in the fasted 1-day group, where ethyl 22:6 disappeared, though it reappeared in the fasted 2-day group.


CONCLUSIONS
These findings demonstrate that skeletal muscles contain high levels of FAEE that are synthesized in the body after ethanol exposure. The concentration of FAEE in skeletal muscle in this study was very similar to FAEE concentration in the liver. This differs from previous studies suggesting a low concentration of skeletal muscle FAEE with ethanol exposure.
Salem
Raneem O
RO
Massachusetts General Hospital and Harvard Medical School, Division of Laboratory Medicine, Boston, MA 02114, USA.
Laposata
Michael
M
Rajendram
Rajkumar
R
Cluette-Brown
Joanne E
JE
Preedy
Victor R
VR
D000009:Abdominal Muscles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000428:Alcohol Drinking; D000818:Animals; D015992:Body Mass Index; D001835:Body Weight; D002492:Central Nervous System Depressants / Q000378:metabolism*; D004952:Esters / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005227:Fatty Acids / Q000096:biosynthesis* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006321:Heart / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004952:Esters; D005227:Fatty Acids; D000431:Ethanol