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.
Med Hypotheses 1980 Sep
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

Fatty liver syndrome or hepatic lipidosis (HL) is a condition thought to contribute to an increased incidence of peripartum disease, reduced response to therapy and decreased fertility in dairy cows. This syndrome is characterized by excess triglyceride (TG) accumulation in the liver and apparent decreased hepatic lipoprotein output. In lactating rats, a similar condition results from feeding an inositol-deficient diet. It is also characterized by excess hepatic TG accumulation and decreased hepatic lipoprotein output. Myo-inositol is a necessary component of the phospholipid phosphatidyl-inositol, which is an important membrane constituent. Myo-inositol occurs in feed mainly as the inositol hexaphosphate phytic acid. Phytic acid is undigestible by the monogastric but rumen phytases are assumed to adequately hydrolyze it. In early lactation dairy cows, lipid mobilization is intense, and the myo-inositol requirement may exceed the dietary supply or availability. Myo-inositol is being tested in a field trial as a potential lipotropic agent for dairy cows. Preliminary results suggest no lipotropic benefit from added myo-inositol.
J Anim Sci 1984 Sep
PMID:Inositol as a lipotropic agent in dairy cattle diets. 638 80

Needle biopsy specimens of liver were obtained from six control subjects with histologically normal liver and 11 chronic alcoholics with fatty liver. Micro- and macro-lipid droplet fractions were isolated by differential flotation. These fractions, together with the sedimenting membranes, were assayed for cholesterol, cholesteryl ester, phospholipid, free fatty acids and triglyceride. Electron microscopy demonstrated marked differences in the range of lipid droplet sizes in the two fractions and biochemical analysis suggested that the microdroplet lipid corresponded to pre-very low density lipoprotein (VLDL) particles. Studies on biopsies from patients with alcoholic fatty liver showed a 2-3-fold increase in triglyceride in both lipid droplet fractions but most of the accumulating triglyceride was sedimentable and membrane-bound. Needle biopsy specimens from two patients with alcoholic fatty liver were fractionated with a vertical pocket re-orientating rotor. The principal organelles were separated and the subcellular distribution of triglyceride, phospholipid and free cholesterol determined. Triglyceride showed a bimodal distribution to a particulate fraction tentatively located to Golgi particles and to droplet-lipid remaining in the sample layer.
Clin Sci (Lond) 1984 Sep
PMID:Isolation of micro- and macro-droplet fractions from needle biopsy specimens of human liver and determination of the subcellular distribution of the accumulating liver lipids in alcoholic fatty liver. 646 37

Chicks were given biotin-deficient diets containing either suboptimal (low) or supraoptimal (high) concentrations of protein from 1-d-old until they were used during their fourth week of life. The low-protein diet predisposed chicks to develop fatty liver and kidney syndrome and the high-protein diet to develop classical biotin deficiency signs. Two other groups, as controls, received biotin-supplemented rations. Low dietary protein increased lipogenesis by isolated hepatocytes but had little effect on gluconeogenesis compared to high dietary protein. Low dietary protein decreased activities of hepatic isocitrate dehydrogenase (EC 1.1.1.42), fructose-1,6-bisphosphatase (EC 3.1.3.11) and glucose-6-phosphatase (EC 3.1.3.9; GP) and increased activities of fatty acid synthase (FAS), citrate cleavage enzyme (EC 4.1.3.8; CCE) and malate dehydrogenase (decarboxylating) (EC 1.1.1.39). When biotin deficiency was superimposed, the rate of lipogenesis by isolated hepatocytes (from fed birds) was decreased. Gluconeogenesis from lactate and glycerol was also depressed. Activity of GP was further decreased by biotin deficiency on the low-protein regimen and FAS and CCE were further increased. PK activity was increased by biotin deficiency.
Br J Nutr 1983 Sep
PMID:The effect of biotin deficiency and dietary protein content on lipogenesis, gluconeogenesis and related enzyme activities in chick liver. 661 62

Fatty liver was induced in the rats shortly after administration of cycloheximide, ethionine, orotic acid, monensin or colchicine. It was strongly suggested that derangements in one or more of the hepatic lipoprotein metabolic steps, which occur at the levels of endoplasmic reticulum, Golgi apparatus and secretory vacuoles lead to an accumulation of triglyceride within hepatocytes.
Acta Pathol Jpn 1983 Sep
PMID:Ultrastructural changes of hepatocyte organelles induced by chemicals and their relation to fat accumulation in the liver. 665 Jan 71

Using fractionation, subcellular pathogenesis of the fatty liver was investigated. Floating lipids were isolated from a small amount of the liver obtained by needle biopsy. The volume of the floating lipids was correlated to the grading of fat infiltration of the intact tissue. Of lipid-rich particles bound by membranous structures, the volume of lipolysosomes in the patients with liver damage associated with diabetes mellitus was greater than that of alcoholics. Hypercholesterolemia was another feature characteristic of the liver disease exhibiting lipolysosome proliferation. These observations suggest a lysosomal involvement in fatty degeneration of the liver in diabetics through an overload of cholesterol.
Acta Pathol Jpn 1983 Sep
PMID:Electron microscopic study on the floating lipids of human liver. Lysosomal involvement in the fatty liver associated with diabetes mellitus. 665 Jan 72

The role of the Ito cells in perivenular and intralobular scarring in alcoholic liver disease was examined morphologically. There was a substantial decrease in the number of Ito cells in the midzone of the hepatic lobule in both fatty liver and alcoholic hepatitis as judged by light microscopy. By electron microscopy, however, an increase in "activated" Ito cells or a few fibroblasts were found in small foci of fibrosis in association with inflammation and hepatocellular degenerative changes in most cases of alcoholic hepatitis. Cytoplasmic protrusions of activated Ito cells extended to the hepatocytes undergoing degenerative changes including Mallory body formation. There was an apparent transition from Ito cells to activated Ito cells and to fibroblasts. It is suggested that Ito cells may play a role in perivenular and intralobular fibrosis in alcoholic hepatitis.
Arch Pathol Lab Med 1983 Sep
PMID:The role of the Ito cell in perivenular and intralobular fibrosis in alcoholic hepatitis. 668 40

Drug damage to the liver can be divided into two types: Type I damage is predictable, dose-dependent and appears in most patients treated. Type II lesions are not predictable, are not dose-dependent and occur in only a small percentage of patients. Clinically they can be differentiated into (1) a cytotoxic form (clinical picture: fatty liver, virus hepatitis), (2) a cholestatic form (clinical picture: obstructive jaundice) and (3) a mixed form. In the present study, liver damage due to the following drugs, as important examples of the different types of damage, are dealt with in greater detail: isoniazid (unpredictable damage of the cytotoxic type), methotrexate (predictable damage of the cytotoxic type) chlorpromazine (unpredictable damage of the cholestatic type) and finally estrogens or oral contraceptives (damage of the cholestatic type and other damage to the hepatobiliary system).
MMW Munch Med Wochenschr 1980 Sep 05
PMID:[Damage to liver and biliary tracts by long-term drug therapy (author's transl)]. 677 79

Excessive alcohol ingestion results in profound derangements of lipid and lipoprotein metabolism, reflecting the effects of ethanol on peripheral and hepatic lipid metabolism and its toxic effects on hepatic function. The alterations in plasma lipids and lipoproteins are secondary to complex abnormalities of lipoprotein synthesis, secretion and catabolism. The major effects of alcohol include fatty liver secondary to excessive triglyceride synthesis, resulting in an imbalance between synthesis and hepatic secretion; hypertriglyceridemia and hypercholesterolemia; defective plasma cholesterol esterification; and decreased high-density lipoprotein cholesterol. In patients with severe alcoholic hepatitis, the plasma lipoproteins have an abnormal structure and apoprotein composition. Although these changes are usually reversible with abstinence from alcohol (if liver function returns to normal), they indicate serious effects of alcohol on the liver, which may culminate in cirrhosis and hepatic insufficiency. These effects of alcohol on lipids and lipoproteins should be contrasted with the elevation in high-density lipoprotein cholesterol concentration produced by moderate alcohol intake and the possibility that this increase may protect against the development of atherosclerotic disease.
Circulation 1981 Sep
PMID:Lipid and lipoprotein abnormalities in alcoholic liver disease. 702 Sep 88

Among 112 patients with alcoholic liver injury, 45 had alcoholic fibrosis. The incidence of alcoholic fibrosis was 40.2% which was the highest among various types of alcoholic liver injury (fatty liver; 3.6%, alcoholic hepatitis; 2.7% and liver cirrhosis; 31.3%). Clinical features of alcoholic fibrosis were milder than those of liver cirrhosis and more severe than those of fatty liver. The mean laboratory values in alcoholic fibrosis were significantly different from those in fatty liver and liver cirrhosis. The laboratory data were well correlated with the presence of pericellular fibrosis and thickening of the terminal hepatic venule, but only partially with hepatic cell necrosis and not with fatty metamorphosis. Two patients with alcoholic fibrosis who developed cirrhosis without any clinical and histological features of hepatitis were observed during 5-yr follow-up. These results indicate that alcoholic fibrosis is the most common type of alcoholic liver injury in Japan and is an independent clinicopathological entity distinct from the classical types of alcoholic liver injury. Pericellular fibrosis and thickening of the terminal hepatic venule which are the main histological features of alcoholic fibrosis may play an important role in its transition to liver cirrhosis.
Am J Gastroenterol 1982 Sep
PMID:Clinicopathological study of alcoholic fibrosis. 711 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>