linoleic-acid and Liver-Cirrhosis

Defective platelet aggregation and reduced platelet production of thromboxane A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis. We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty acids on platelet function and plasma and membrane fatty acids in patients with liver cirrhosis.. In a double-blind study, 15 patients with cirrhosis and defective aggregation were randomized to receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/day of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively).. Under baseline conditions, patients showed elevated concentrations of monounsaturated fatty acids and a reduction in polyunsaturated fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two key enzymes in the pathway leading to arachidonic acid, were significantly reduced in the group of patients. In the GLA group, a significant increase in the levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after supplementation. No significant changes were observed in the OA group. The levels of arachidonic acid did not change significantly in either group of patients. Platelet aggregation to collagen was unchanged in the GLA group, but significantly improved in the OA group.. These results show that supplementation with precursors of arachidonic acid is ineffective in elevating plasma or membrane arachidonate levels and does not improve platelet aggregation, suggesting that synthesis of arachidonic acid through the delta5 desaturase cannot be correspondingly activated or that incorporation/retention of the produced fatty acid into lipids is impaired. The increased platelet aggregation in the OA group is likely to be explained by the effect of oleic acid contained in the diet, the effects of which may have been counteracted by the elevation in 20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.

Topics: Aged; Blood Platelets; Dietary Supplements; Double-Blind Method; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Linoleic Acid; Lipids; Liver Cirrhosis; Male; Membrane Lipids; Middle Aged; Oleic Acid; Platelet Aggregation; Reference Values; Thromboxane A2; Vitamin E

The antidiabetic drug pioglitazone ameliorates insulin resistance by activating the transcription factor PPARγ. In addition to its blood glucose-lowering action, pioglitazone exerts pleiotropic effects including amelioration of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). The mechanism by which pioglitazone achieves this latter effect has remained unclear, however. We here show that pioglitazone administration increases the amount of linoleic acid (LA) metabolites in adipose tissue of KK-Ay mice. These metabolites are produced by lactic acid bacteria in the gut, and pioglitazone also increased the fraction of Lactobacillus in the gut microbiota. Administration of the LA metabolite HYA (10-hydroxy-cis-12-octadecenoic acid) to C57BL/6 J mice fed a high-fat diet improved liver histology including steatosis, inflammatory cell infiltration, and fibrosis. Gene ontology analysis of RNA-sequencing data for the liver revealed that the top category for genes downregulated by HYA treatment was related to extracellular matrix, and the expression of individual genes related to fibrosis was confirmed to be attenuated by HYA treatment. Mechanistically, HYA suppressed TGF-β-induced Smad3 phosphorylation and fibrosis-related gene expression in human hepatic stellate cells (LX-2). Our results implicate LA metabolites in the mechanism by which pioglitazone ameliorates liver fibrosis, and they suggest that HYA is a potential therapeutic for NAFLD/NASH.

Topics: Animals; Diet, High-Fat; Fibrosis; Gastrointestinal Microbiome; Hepatic Stellate Cells; Humans; Linoleic Acid; Liver; Liver Cirrhosis; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Pioglitazone; Transforming Growth Factor beta

The specific purpose of this study was to investigate the effects of dietary olive oil on hepatic fibrosis induced by chronic administration of carbon tetrachloride (CCl(4)) in the mouse. In addition, the effects of oleic acid, a major component of olive oil, on activation of hepatic stellate cells (HSCs) were investigated in vitro.. Mice were fed liquid diets containing either corn oil (control, AIN-93) or olive oil (6.25 g/L) throughout experiments. Animals were treated with CCl(4) for 4 weeks intraperitoneally. The mRNA expression of TGF-beta1 and collagen 1alpha2 (col1alpha2) in the liver was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). The HSCs were isolated from mice, and co-cultured with either oleic acid (100 microM) or linoleic acid (100 microM) for 2 days. The expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunohistochemistry. In addition, the production of hydroxyproline was determined.. Serum alanine aminotransferase levels and the mRNA expression of TGF-beta and collalpha2 were significantly reduced by treatment of olive oil. Dietary olive oil blunted the expression of alpha-SMA in the liverand liver injury and hepatic fibrosis were prevented by treatment of olive oil. The number of alpha-SMA positive cells was significantly lower in HSCs co-cultured with oleic acid than in those co-cultured with linoleic acid. Concentration of hydroxyproline in culture medium was significantly lower in cells co-cultured with oleic acid than in the control.. Dietary olive oil prevents CCl(4)-induced tissue injury and fibrosis in the liver. Since oleic acid inhibited activation of HSCs, oleic acid may play a key role on this mechanism.

Topics: Actins; Animals; Carbon Tetrachloride; Collagen Type I; Corn Oil; Dietary Fats, Unsaturated; Gene Expression Regulation; Hepatic Stellate Cells; In Vitro Techniques; Linoleic Acid; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Oleic Acid; Olive Oil; Plant Oils; Transforming Growth Factor beta1

In acute liver failure the liver has to regenerate, which may increase the consumption of essential fatty acids. Nutritional support consists mainly of infusion of glucose. It is therefore possible that essential fatty acid deficiency may develop in such patients.. Plasma phospholipid composition was studied in healthy controls (n=11), in patients with acute liver failure, (n=10), in patients with stable cirrhosis (n=7), and in patients with acute on chronic liver disease with hepatic encephalopathy (n=6). The influence of 2 days of fat-free diet followed by infusion of glucose was studied in five healthy controls.. The ratio between the sums of nonessential/ essential fatty acids, (n-7+n-9)/(n-3+n-6), was higher in patients with acute liver failure (0.73+/-0.17) compared to healthy controls (0.35+/-0.06, p<0.001). The ratio was also higher in patients with acute on chronic liver disease (1.11+/-0.39) compared to patients with cirrhosis (0.61+/-0.18, p<0.01). These differences were mainly due to low levels of linoleic acid and high levels of oleic acid in the patients with acute liver failure and acute on chronic liver disease. Two days of fat-free diet followed by infusion of glucose did not change this ratio (0.40+/-0.04 vs. 0.47+/-0.05, NS) in healthy controls. The essential fatty acid deficiency indicator eicosatrienoic acid was detectable in 2 out of 11 controls, in 5/10 with acute liver failure, in 7/7 with cirrhosis, and in 6/7 with acute on chronic liver disease.. Acute severe deterioration of liver function was associated with changes in the fatty acid composition of plasma phospholipids suggestive of essential fatty acid deficiency.

Topics: Acute Disease; Adult; Chronic Disease; Dietary Fats; Fatty Acids; Female; Glucose; Hepatic Encephalopathy; Humans; Linoleic Acid; Liver Cirrhosis; Liver Diseases; Liver Failure; Male; Middle Aged; Oleic Acid; Phospholipids; Reference Values

The fasting concentration of free fatty acids (FFA) in the ascitic fluid was determined in 14 patients with malignant ascites and in 19 patients with liver cirrhosis. In malignant ascites FFA levels were increased more than three times when compared with the levels in cirrhotic ascites (5.241 +/- 0.493 vs. 1.558 +/- 0.170 mumol/ml; P < 0.0001). Palmitic acid was the most representative saturated FFA (which together accounted for 2.499 +/- 0.323 vs. 0.833 +/- 0.064 mumol/ml; P < 0.0001), while unsaturated FFA (2.741 +/- 0.298 vs. 0.725 +/- 0.111 mumol/ml; P < 0.001) were represented, in decreasing order, by oleic, linoleic and arachidonic acids. The ratio of unsaturated to saturated FFA was higher in neoplastic patients (1.35 +/- 0.29 vs. 0.826 +/- 0.065 P < 0.05). Albumin concentration in ascitic fluid of neoplastic patients was 22.44 +/- 1.35 g/l, while that of cirrhotic patients was 8.19 +/- 0.32 g/l, P < 0.0001. A close relationship (R2 = 95.14%) between albumin concentration in ascitic fluid and levels of total FFA was found. These data support the hypothesis that the elevation of FFA in ascitic fluid allows discrimination between malignant and non-malignant ascites.

Topics: Adult; Aged; Albumins; Arachidonic Acid; Ascitic Fluid; Carcinoma, Hepatocellular; Fatty Acids, Nonesterified; Female; Humans; Linoleic Acid; Linoleic Acids; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Peritoneal Neoplasms

1. Functional renal failure (FRF) in cirrhosis with ascites could be related to an inappropriately low renal prostaglandin (PG) production. To investigate whether the impaired renal PG synthesis in these patients is related to a PG precursor fatty acid deficiency, serum levels of linoleic and arachidonic acids and the urinary excretion of PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured in 10 normal subjects, 17 non-azotaemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and FRF. 2. Serum linoleic acid levels were similar in the three groups studied. Both groups of cirrhotic patients showed lower arachidonic acid levels than normal subjects; however, non-azotaemic cirrhotic patients and patients with FRF did not differ in relation to serum arachidonic acid. 3. Non-azotaemic cirrhotic patients had higher urinary PGE2, 6-keto-PGF1 alpha and TxB2 excretion than normal subjects and cirrhotic patients with FRF. Patients with FRF showed similar urinary PGE2 and TxB2 and lower urinary 6-keto-PGF1 alpha than normal subjects. In all cirrhotic patients no significant correlation was found between serum linoleic and arachidonic acid levels and urinary PGs. 4. In seven patients with FRF an acute intravenous infusion of linoleic acid induced a marked increase in serum levels of this fatty acid. However, no increase in serum arachidonic acid levels and urinary PG excretion and no improvement in renal function was observed. 5. This study suggests that an arachidonic acid deficiency is present in cirrhotic patients with ascites but that this abnormality is not a major determinant of renal function and PG production in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arachidonic Acid; Arachidonic Acids; Female; Humans; Kidney; Kidney Diseases; Linoleic Acid; Linoleic Acids; Liver Cirrhosis; Male; Middle Aged; Prostaglandins

Intestinal fat absorption was examined in rats with CCl4-induced liver cirrhosis. Marked lymphangiectasia of the small intestine was observed in rats after CCl4 was given subcutaneously biweekly for 10--12 weeks. Intestinal epithelial uptake of linoleic acid administered in the loop was not impaired, but accumulation of lipid droplets in the intestinal epithelial cells and disturbed lymphatic transport of absorbed fat were observed in these rats. These data suggest that lymphostasis of the intestine may play an important role in fat malabsorption in liver cirrhosis.

Topics: Animals; Carbon Tetrachloride; Intestine, Small; Linoleic Acid; Linoleic Acids; Lipids; Liver Cirrhosis; Lymphatic System; Malabsorption Syndromes; Male; Rats; Rats, Inbred Strains

Topics: Amino Acids; Blood; Chemical and Drug Induced Liver Injury; Choline; Glycine max; Hepatitis; Linoleic Acid; Lipotropic Agents; Liver Cirrhosis; Liver Cirrhosis, Experimental; Liver Diseases; Phospholipids; Rats; Research; Sulfacetamide; Toxicology

Topics: Adrenal Cortex Hormones; Ascites; Chlorothiazide; Diet, Sodium-Restricted; Dietary Carbohydrates; Dietary Proteins; Diuretics; Humans; Hypercholesterolemia; Linoleic Acid; Liver Cirrhosis; Organomercury Compounds; Pruritus; Rest; Testosterone; Tolbutamide

Topics: Linoleic Acid; Linoleic Acids; Lipidoses; Liver Cirrhosis; Liver Cirrhosis, Biliary