Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.
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PMID:A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. 625 73

Five groups of NMRI mice were fed ethanol or sucrose in a nutritionally adequate liquid diet for 9 days. The dietary fat consisted of olive oil with the fatty acid composition 18:1 77%, 18:2 10%, 18:0 and 16:0 12%. The ethanol treated groups received 5% w/v ethanol (E) or isocaloric sucrose (S). Two groups (S- and E-) received the diet without supplement. In two groups (S+ and E+) 7% of the fat was exchanged for arachidonic acid (20:4). In a fifth group (IE+) treated with ethanol and arachidonic acid the diet also contained indomethacin (10 mg/l). The mean intake of ethanol was about 20 g/kg/day. After 9 days animals were killed and liver lipids analyzed after Folch extraction. The post mortem accumulation of prostaglandin E2 in the kidney was measured by GC-MS. Dietary 20:4 was found to protect mice against fatty liver caused both by a high fat diet alone and in combination with ethanol. The liver triglycerides were 30.7 +/- 4.3 (S-), 46.1 +/- 6.9 (E-), 6.8 +/- 0.4 (S+) and 19.4 +/- 1.8 (E+). Prostaglandin levels in the kidney were depressed by ethanol treatment. Indomethacin gave variable degrees of PG synthesis inhibition. The degree of liver triglyceride accumulation in the IE+ group was inversely proportional to the degree of PG synthesis. The data suggest a role for liver 20:4 cyclooxygenase metabolites in fatty liver caused by high fat diets and ethanol.
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PMID:Dietary arachidonic acid protects mice against the fatty liver induced by a high fat diet and by ethanol. 643 43