Fatty Liver Changes Research Articles

Fatty acid changes in liver and plasma lipid fractions after safflower oil was fed to rats deficient in essential fatty acids.

1. Fatty acid patterns of liver and plasma triglycerides, phospholipids and cholesteryl esters were determined at intervals during 24hr. after essential fatty acid-deficient rats were given one feeding of linoleate (as safflower oil). 2. Liver triglyceride, phospholipid and cholesteryl ester fatty acid compositions did not change up to 7hr. after feeding. Between 7 and 10hr., linoleic acid began to increase in all fractions, but arachidonic acid did not begin to rise in the phospholipid until 14-19hr. after feeding. 3. Oleic acid and eicosatrienoic acid in liver phospholipid began to decline at about the time that linoleic acid increased, i.e. about 9hr. before arachidonic acid began to increase. 4. Changes in linoleic acid, arachidonic acid and eicosatrienoic acid in phosphatidylcholine resembled those of the total phospholipid. Phosphatidylethanolamine had a higher percentage content of arachidonic acid before the linoleate was given than did phosphatidylcholine, and after the linoleate was given the fatty acid composition of this fraction was little changed. 5. The behaviour of the plasma lipid fatty acids was similar to that of the liver lipids, with changes in linoleic acid, eicosatrienoic acid and arachidonic acid appearing at the same times as they occurred in the liver. 6. The results indicated that linoleic acid was preferentially incorporated into the liver phospholipid at the expense of eicosatrienoic acid and oleic acid. The decline in these fatty acids apparently resulted from their competition with linoleic acid for available sites in the phospholipids rather than from any direct replacement by arachidonic acid.

Impaired carbohydrate and lipid metabolism and liver fatty change in human viral hepatitis

Impaired carbohydrate and lipid metabolism and liver fatty change in human viral hepatitis

肝疾患における肝Glucose-6-phosphate dehydrogenase, 6-Phosphogluconate dehydrogenaseおよびCitrate cleavage enzyme活性と肝の脂肪沈着について 第1編

The activities of Glucose-6-phosphate dehydrogenase, 6-Phosphogluconate dehydrogenase and Citrate cleavage enzyme, of which increase is known to be associated with an enhanced lipogenesis in experimental animals, were measured in the liver tissues from the patients with liver diseases.1) The activities of these enzymes were significantly increased in the convalescent stage of acute hepatitis, while no significant changes were found in chronic hepatitis (active or inactive), liver cirrhosis and fatty liver.2) No apparent correlation was found between the activities of these enzymes and the degree of hepatic fatty infiltration in these liver diseases, suggesting that hepatic lipogenesis might not play a majar role in fatty change of liver encountered in the course of the liver diseases. Alternatively, the increased enzyme activities might reflect some other metabolic alterations associated with hepatic injury.

Fatty Acid Changes in Liver Produced by Protein Deficiency and by Methionine or Cystine Fed to Rats in a Protein-free Ration

Liver fatty acid changes were studied during the development of an uncomplicated protein deficiency and in protein deficiency complicated by the addition of 0.30% methionine to the protein-free diet. (Only slightly fatty livers are produced in uncomplicated protein deficiency, whereas very fatty livers are produced by including methionine or cystine in a protein-free diet.) In general the fatty acid changes in adult male rats fed either diet followed similar patterns, although the extent of the changes was different. The increase in liver fatty acids could be accounted for almost entirely by elevations in palmitate, oleate, and linoleate. When dietary fat (corn oil) was omitted, however, the contribution by linoleate was depressed almost completely, being substituted for by palmitoleate and oleate. Significant loss of all fatty acids from the phospholipid fraction occurred. The presence of methionine in the protein-free diet in general protected against the loss of fatty acids from this fraction. Palmitoleate and oleate substituted for linoleate in the phospholipid fraction when dietary corn oil was omitted. The fat in the fatty livers produced by methionine or cystine was accounted for almost entirely by marked increases in neutral lipid palmitate, oleate, and linoleate. Cystine, methionine, and valine fed in the protein-free diet increased arachidonate concentration in the neutral lipid fraction, whereas leucine depressed it almost completely. When protein repletion was begun, all fatty acids except linoleate and arachidonate returned to extremely high values in the livers of the protein-free rats and to a much less extent in livers of the rats previously fed methionine in the protein-free diet. These studies suggest the following general conclusions: An as yet unknown mechanism allows the production of fatty livers when methionine is present in a protein-free ration. If linoleate is present in the diet, it accounts for a large part of the fat; but palmitoleate and oleate can substitute for linoleate. An imbalance between fat-synthesizing systems and fat-secreting systems in the liver probably accounts for a very large, transient increase in fatty acid concentrations when protein is reintroduced into the diet of protein-deficient animals. The enzyme systems involved in producing arachidonate from linoleate appear to be sharply impaired by protein deficiency. Methionine fed in a protein-deficient diet, however, almost completely prevents this effect.

Homocystinuria: Clinical and pathological review of ten cases

Homocystinuria is an inborn error on the pathway of the metabolism of methionine due to an absence of cystathionine synthetase in brain and liver. Clinical experience with ten cases occurring in seven families shows a consistent picture characterized by mental retardation, ectopia lentis, fine, fair hair, malar flush, thromboembolic and cardiovascular disease, skeletal deformities, and fatty change of liver. Family pedigrees suggest an autosomal recessive mode of inheritance. There are increased amounts of methionine and homocystine in the plasma and cerebrospinal fluid with increased excretion of homocystine in the urine. Fragmentation of the elastic tissue of large arteries is accompanied by a decrease in the glycoprotein and protein polysaccharide matrix. The fatty change of liver is due to a twofold increase in the neutral lipids. The brain shows focal necrosis and gliosis, and there are degenerative changes of the zonular fibers of the lens on light and electron microscopy. Homocystinuria is an inborn error on the pathway of the metabolism of methionine due to an absence of cystathionine synthetase in brain and liver. Clinical experience with ten cases occurring in seven families shows a consistent picture characterized by mental retardation, ectopia lentis, fine, fair hair, malar flush, thromboembolic and cardiovascular disease, skeletal deformities, and fatty change of liver. Family pedigrees suggest an autosomal recessive mode of inheritance. There are increased amounts of methionine and homocystine in the plasma and cerebrospinal fluid with increased excretion of homocystine in the urine. Fragmentation of the elastic tissue of large arteries is accompanied by a decrease in the glycoprotein and protein polysaccharide matrix. The fatty change of liver is due to a twofold increase in the neutral lipids. The brain shows focal necrosis and gliosis, and there are degenerative changes of the zonular fibers of the lens on light and electron microscopy.

Biochemical changes in fatty liver induced by choline or threonine deficiency. Part II. Various hepatic enzymic activities during the development of fatty livers in rats

The activities of various hepatic enzymes were determined in choline-deficient rats over an 8-day experimental period and in rats fed a low-protein diet primarily deficient in threonine over a 30-day experimental period. Supernatant fractions (10,000 g) prepared from rat liver homogenates were assayed for glucose-6-phosphate (+6-phosphogluconate) dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase, α-glycerophosphate dehydrogenase, malic dehydrogenase, and glucose-6-phosphatase. Mitochondria isolated from rat liver homogenates were assayed for the electron transport system which catalyzes the DPN-mediated oxidation of TPNH by cytochrome c, isocitrate dehydrogenase, and α-glycerophosphate dehydrogenase. Of the enzymes assayed in the supernatant fractions (10,000 g) of rat liver homogenates, only the dehydrogenases of the pentose phosphate pathway were significantly altered. A general increase in the specific activities of these enzymes occurred in all groups of rats irrespective of diet. It was concluded that the alteration in activity of these dehydrogenases may be indirectly related to the development of fatty liver by providing a source of available TPNH which could be utilized in the reductive reactions accompanying fat synthesis. Of the mitochondrial enzymes studied, only the electron transport system which catalyzes the DPN-mediated oxidation of TPNH was significantly decreased in fatty livers. The data did not permit assigning a direct cause or effect relationship between the lowered specific activity of this electron transport system and increased hepatic fat deposition; however, the correlation of lowered activity for this electron transport pathway and increased hepatic fat content was consistent.

Biochemical changes in fatty liver induced by choline or threonine deficiency. Part I. Levels of individual pyridine nucleotides

The amounts of DPN, DPNH, TPN, and TPNH expressed as mμmoles per milligram of liver nitrogen or mμmoles per liver of choline- or threonine-deficient rats were not significantly different from amounts observed in control rats receiving adequate dietary choline or threonine. In accord with results previously reported by others, mμmoles of total pyridine nucleotidcs per gram of fresh liver were decreased by either choline or threonine deficiency. A 24-hour period of fasting resulted in a significant decrease in the mμmoles of DPN and TPNH per milligram of liver nitrogen.

Chronic oral toxicity of aldrin and dieldrin in rats and dogs

The results of feeding rats and dogs diets containing aldrin and dieldrin for 2 yr are reported. When groups of 24 (12 male and 12 female) rats were placed on diets containing 0 (controls), 0·5, 2, 10, 50, 100 or 150 ppm of aldrin or dieldrin at 3 weeks of age and continued on their respective diets for 2 yr, neither aldrin nor dieldrin affected growth. Survival was markedly decreased among rats on either supplement at 50 ppm or greater, and a dose-response relationship occurred. Liver weight to body weight ratios were significantly increased in rats at all levels of aldrin and dieldrin fed, although not necessarily for both sexes at each level. Both gross and microscopic changes were caused by aldrin and dieldrin at all levels given. In rats on the higher dose levels distended and haemorrhagic urinary bladders, enlargement of the liver, and an increased incidence of nephritis occurred. Rats, fed smaller amounts of either insecticide, showed a general increase in tumour incidence, which was almost doubled. In rats on all dose levels the characteristic microscopic liver lesions, which occur in rodents given any of a number of chlorinated insecticides, were found. Such liver change was minimal in rats on 0·5 ppm of dieldrin, and especially, of aldrin. Among rats on 50 ppm or more this change was generally pronounced. In a total of 26 dogs, fed aldrin or dieldrin at 0·2–10 mg/kg/day for up to 25 months, those on 0·5 mg or more showed gross toxic effects, including loss of weight and convulsions, and they died progressively earlier with increasing dose level. Microscopic effects were limited to fatty degenerative changes in liver and kidney and bone marrow changes (reduced cellularity, particularly in the erythroid line) in those dogs on 1 mg/kg/day or more of either insecticide. Similar effects occurred in dogs on 0·5 mg dieldrin; however, no microscopic change was noted in dogs on 0·5 mg aldrin. No effect, gross or microscopic, was seen in dogs on 0·2 mg of either insecticide.

Serum enzyme and histopathologic changes in rats after cold exposure.

SummaryExposure of 2 groups of dry rats 16 hours to 1.7 and −5°C and a third group of wet rats 5 hours to 1.7°C on 2 successive days significantly increased levels of serum glutamic oxalacetic transaminase, serum aldolase and blood urea nitrogen. The blood urea nitrogen in all 3 groups and serum enzyme values in the 1st group were normal in 24 hours. The serum enzyme values in the 2nd and 3rd groups were normal in 3 and 6 days respectively. Mean body temperatures in the 3 groups at the end of the cold exposures were 38.2, 36.7 and 33°C respectively. The transient rise in serum enzymes coincided with a transient decrease in mean hematocrit and in glycogen in liver and muscle and lipid in the adrenal cortex, and leukocytosis. Many rats also showed transient fatty changes in the liver and, less frequently, in the kidney and heart

Effect of carbon tetrachloride poisoning on potassium, sodium and water content of liver mitochondria.

A physiological test of mitochondrial function, which measures the ability of the mitochondria to concentrate potassium in vitro, was employed in a study of carbon tetrachloride-induced hepatotoxicity. The force feeding of carbon tetrachloride resulted in a) a reduction in the potassium content of rat liver mitochondria, b) an impairment in the ability of potassium depleted mitochondria to reaccumulate potassium and c) an increased water content of the mitochondria. The changes could be demonstrated unequivocally at 10.5 hr. and became extensive at 20 hr. The results do not support the view that the increase in liver fat is the direct result of a lesion in the mitochondria since the time course of impairment in mitochondrial potassium and water metabolism lags behind the fatty changes of the whole liver.

Production of fatty livers by 4-aminopyrazolo-(3, 4-d)-pyrimidine; toxicological and pathological studies.

Summary and conclusionsThe toxic effects of 4-aminopyrazolo-(3,4-d)-pyrimidine (4-APP) have been studied in mice, rats, cats, and dogs. The agent was found to produce a fatty change in liver which was associated neither with necrosis nor with inflammation. Hepatic insufficiency was evidenced by hyperbilirubinemia, increases in one-stage prothrombin time and decreases in plasma fibrinogen. In rats fat nephrosis and depletion of hematopoietic elements in bone marrow were also seen. Hepatic insufficiency should be anticipated as a possible hazard in clinical trials with 4-APP.

Functional and Fatty Changes in Liver During Chronic Vitamin B Complex Deficiency.

SummaryA chronic vitamin B complex deficiency in dogs on a 41% casein diet produced a marked decrease in voluntary food intake, but liver function tests remained normal and liver sections showed no increase in fat. A similar chronic B complex deficiency using dogs on a 20% casein diet produced an abnormal liver function and fatty changes in liver biopsy specimens. These findings were absent in the inanition and normal control dogs. Therapy with yeast extract restored the liver function to normal and the fatty change in the liver decreased, even though protein and caloric intake were restricted.

Focal Fatty Change of Liver and Focal Cirrhosis

Focal Fatty Change of Liver and Focal Cirrhosis Get access Harold L. Stewart, Harold L. Stewart From the Pathological Laboratories of the Jefferson Medical College and Hospital and the Department of Neoplastic Diseases Search for other works by this author on: Oxford Academic Google Scholar David R. Morgan, David R. Morgan From the Pathological Laboratories of the Jefferson Medical College and Hospital and the Department of Neoplastic Diseases Search for other works by this author on: Oxford Academic Google Scholar Vaughan L. Sprenkel Vaughan L. Sprenkel From the Pathological Laboratories of the Jefferson Medical College and Hospital and the Department of Neoplastic Diseases Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 8, Issue 4, 1 July 1938, Pages 405–421, https://doi.org/10.1093/ajcp/8.4.405 Published: 12 November 2015 Article history Received: 18 October 1937 Published: 12 November 2015