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PubMed2003

435-bp liver regulatory sequence in the liver fatty acid binding protein (L-FABP) gene is sufficient to modulate liver regional expression in transgenic zebrafish.

Liver fatty acid binding protein (L-FABP) is a small protein that is thought to play an important role in the intracellular binding and trafficking of long chain fatty acids in the liver. Expression of the gene encoding the zebrafish liver fatty acid binding protein is regulated by a 435-bp distal region (-1944 to -1510) of the L-FABP promoter. The 435-bp sequence is sufficient for gene activation in the liver primordia (or bud) and continues to be active in the adult liver when positioned adjacent to the SV40 basal promoter and linked directly to green fluorescent protein. The 435-bp sequence region has two distinct liver regulatory elements, A (-1944 to -1623) and B (-1622 to -1510), and contains multiple putative consensus binding sites. The element A sequence includes two consensus HFH and one HNF-1alpha site and the element B sequence includes one consensus HNF-3beta site. Deletion of an internal 435-bp fragment (-1944 to -1510) including the A and B elements totally ablated the liver-specific activity of the zebrafish L-FABP gene promoter. Deletion of either of the two elements reduces the liver activity. Mutation of the HNF-1alpha site or either of the two HFH sites in the A element or the HNF-3beta site in the B element significantly altered specificity in the liver primordia of transient expression embryos. The importance of the HNF-1alpha consensus binding site in the A element and the HNF-3beta consensus binding site in the B element within the 435-bp distal region of the L-FABP promoter region suggests that combinatorial interactions between multiple regulatory factors are responsible for the gene expression of L-FABP in the liver.

Animals↗
PubMed1991

Interaction of fatty acids with recombinant rat intestinal and liver fatty acid-binding proteins.

Intestinal enterocytes contain two homologous fatty acid-binding proteins, intestinal fatty acid-binding protein (I-FABP)2 and liver fatty acid-binding protein (L-FABP). Since the functional basis for this multiplicity is not known, the fatty acid-binding specificity of recombinant forms of both rat I-FABP and rat L-FABP was examined. A systematic comparative analysis of the 18 carbon chain length fatty acid binding parameters, using both radiolabeled (stearic, oleic, and linoleic) and fluorescent (trans-parinaric and cis-parinaric) fatty acids, was undertaken. Results obtained with a classical Lipidex-1000 binding assay, which requires separation of bound from free fatty acid, were confirmed with a fluorescent fatty acid-binding assay not requiring separation of bound and unbound ligand. Depending on the nature of the fatty acid ligand, I-FABP bound fatty acid had dissociation constants between 0.2 and 3.1 microM and a consistent 1:1 molar ratio. The dissociation constants for L-FABP bound fatty acids ranged between 0.9 and 2.6 microM and the protein bound up to 2 mol fatty acid per mole of protein. Both fatty acid-binding proteins exhibited relatively higher affinity for unsaturated fatty acids as compared to saturated fatty acids of the same chain length. cis-Parinaric acid or trans-parinaric acid (each containing four double bonds) bound to L-FABP and I-FABP were displaced in a competitive manner by non-fluorescent fatty acid. Hill plots of the binding of cis- and trans- parinaric acid to L-FABP showed that the binding affinities of the two sites were very similar and did not exhibit cooperativity. The lack of fluorescence self-quenching upon binding 2 mol of either trans- or cis-parinaric acid/mol L-FABP is consistent with the presence of two binding sites with dissimilar orientation in the L-FABP. Thus, the difference in binding capacity between I-FABP and L-FABP predicts a structurally different binding site or sites.

Carrier Proteins↗
PubMed1977

Fatty liver in patients with moderate alcohol consumption, diabetes mellitus and overweight.

A relationship between the occurrence of fatty liver and moderate alcohol intake, maturity onset diabetes, overweight--and combinations of these three factors--was searched for in 112 patients. Fifty-three of 59 patients with moderate alcohol consumption, 49 of 57 overweight patients, and 42 of 51 diabetic patients had fatty liver. Patients who had a moderate alcohol consumption or suffered from a combination of diabetes and overweight were found to have a significantly higher frequency and degree of fatty liver than patients in the control group. Diabetes alone, and overweight alone were not significantly related to fatty liver. Whether the diabetic state was overt of latent, there was no influence on the frequency or degree of fatty liver. A correlation between the degree of overweight and the degree of fatty liver was found only in the group of overweight patients with moderate alcohol consumption. The degree of fatty liver produced by the combination of overweight and diabetes was not significantly increased by moderate alcohol consumption.

Alcoholism↗
PubMed2006

A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver injury. Currently, there are no proven effective therapies available. Atorvastatin is a new 3-hydroxy-3-metylglutaryl coenzyme A reductase inhibitor that reduces lipid serum levels. AIM: To evaluate the effectiveness and safety of atorvastatin in dyslipemid, non-alcoholic fatty liver patients. PATIENTS AND METHODS: We prospectively enrolled 25 patients with NAFLD; 22 of them completed the study. Body mass index, serum lipids, liver function tests and liver density assessed by echography were measured at baseline and after 1, 3, 6, 9 and 12 months of treatment. Normalization of transaminases and/or improvement in liver density were treatment end points. Patients received atorvastatin (10-80 mg/daily) according to basal serum choleresterol levels; additionally, they were given standard weight-loss counselling and encouraged to follow a low fat diet. RESULTS: All 22 patients (14 men, mean age 47 +/- 10 years) had high cholesterol levels at baseline and 11 (44%) also presented high trygliceride levels. After 6 months of treatment, eight patients (36.3%) presented normal transaminase levels. The remaining patients continued treatment for 12 months when 20% of patients presented with normal transaminase levels, while the other patients showed a 10% reduction in basal levels. Mean cholesterol levels were 268.5 +/- 44.2 and 186.8 +/- 14.4 mg/dL before and after treatment, respectively (P < 0.05). The mean body mass index was 27.4 +/- 3.1 at baseline and 26.3 +/- 2.8 kg/cm2 at the end of treatment (P > 0.05). No side effects were reported. CONCLUSIONS: Serum aminotransferase and lipid levels were reduced significantly in all patients with atorvastatin treatment. Therapy with atorvastatin in NAFLD patients with hyperlipidemia was found to be both effective and safe.

Adult↗
PubMed2004

Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.

Mitochondrial generation of reactive oxygen species (ROS) is increased in mice with fatty livers induced by genetic obesity, chronic consumption of ethanol, or methionine/choline-deficient diets. Both nuclear and mitochondrial (mt) DNA are targets for ROS-induced damage and accumulate hydroxylated bases, such as 8-hydroxy-2'-deoxyguanosine (8-oxoG) and base substitution of adenine with 8-oxoG (A*8-oxoG), that introduce mutations that promote cancer as well as cell death. The mammalian homolog of the bacterial DNA mismatch repair enzyme MutY (MYH) removes A*8-oxoG from nuclear and mtDNA, reduces 8-oxoG accumulation, and restores genomic stability after ROS exposure. Cumulative damage to mtDNA occurs as fatty liver disease progresses. Therefore, differences in hepatic MYH activity may influence the severity of fatty liver disease. To evaluate this hypothesis, we compared mtH2O2 production, MYH expression, oxidative DNA damage, and hepatocyte death in healthy mice and different mouse models of fatty liver disease. The results show that diverse causes of steatohepatitis increase mtROS production, limit repair of mtDNA, and oxidatively damage DNA. However, there are important differences in the DNA repair response to oxidant stress among mouse models of fatty liver disease. Independent of the degree of mtROS generation, models with the least MYH exhibit the greatest accumulation of 8-oxoG and the most hepatocyte death. These findings raise the intriguing possibility that inherited or acquired differences in DNA repair enzyme activity may underlie some of the interindividual differences in fatty liver disease outcomes.

Animals↗
PubMed1989

Biosynthesis of hippurate, urea and pyrimidines in the fatty liver: studies with rats fed orotic acid or a diet deficient in choline and inositol, and with genetically obese (Zucker) rats.

The activities of pathways for the biosynthesis of hippurate, urea and pyrimidines in hepatocytes isolated from lean livers were compared with those from three sources of fatty liver: a) the genetically obese Zucker rat, b) Sprague-Dawley rats fed a diet deficient in choline and inositol, and c) Sprague-Dawley rats fed a diet supplemented with orotic acid. The capacity for hippurate synthesis was not significantly affected by fat accumulation, but ureagenesis from saturating ammonia and ornithine was diminished about 50% in all models when fat content rose above 12% wet wt of liver. Pyrimidine biosynthesis under these conditions was similarly diminished with fat accumulation. Ureagenesis was inhibited by sodium benzoate in hepatocytes from lean livers, but not in hepatocytes from fatty livers. Other results suggest that higher rates of ureagenesis than could be achieved with the fatty liver are required in order to demonstrate inhibition by benzoate. Incorporation of [14C]NaHCO3 into orotate was also inhibited by sodium benzoate, but in hepatocytes from fatty as well as lean livers. The metabolic basis for impairment of ureagenesis and pyrimidine biosynthesis in the fatty liver requires further study. That the capacity for hippurate synthesis was not significantly affected suggests a pathway-specific mechanism.

Ammonium Chloride↗
PubMed2005

Psammomys obesus (sand rat), a new animal model of non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that includes a spectrum of clinicopathologic conditions ranging from steatotosis to cirrhosis and liver failure. NAFLD is usually associated with features of the metabolic syndrome. No established therapies can be offered to patients with NAFLD. An appropriate animal model of NAFLD would be of help in understanding the mechanisms of the disease and in testing novel therapeutic modalities. Available animal models, such as ob/ob and db/db mice, are unsatisfactory since they show only partial resemblance to human NAFLD. Psammomys obesus (sand rat) is a well-established model of type-2 diabetes and obesity, which shares most metabolic parameters of the human metabolic syndrome. In the present study, we hypothesized that P. obesus will also show features of non-alcoholic fatty liver disease. METHODS: Experimental and control animals were fed normal rat chow or either chow to which fiber (30% wheat straw) was added for 6-18 weeks. Body weight and capillary glucose were measured regularly. At sacrifice blood samples, liver and epididymal fat were obtained. Histology of the liver was blindly determined by a pathologist. RESULTS: The experimental group showed increased body weight, liver and abdominal fat pad mass, raised plasma glucose, insulin and lipids. Also, alanine-aminotransferase (189+/-76 IU versus 86+/-26 IU; p<0.0001) was significantly higher in the experimental than the control group. Microscopic examination of liver tissue demonstrated marked macrovesicular fat infiltration in the experimental group while it was histologicaly normal in the control animals (liver fat score 1.7+/-1.0 and 0.2+/-0.4; p<0.0001, respectively). CONCLUSIONS: Fed a calorie-rich diet P. obesus develops a syndrome, which shares metabolic, laboratory and histopathologic characteristics compatible with human NAFLD.

Abdomen↗
PubMed2006

Mesenteric fat thickness as an independent determinant of fatty liver.

OBJECTIVE: Mesenteric fat is drained by the portal circulation and has been suggested to be a key component in obesity-related health risk, notably the metabolic syndrome. There are increasing epidemiological and experimental data showing that fatty liver is another component of this multifaceted syndrome. Given their intimate anatomical and physiological relationships, we hypothesized that mesenteric fat thickness may be independently associated with the risk of fatty liver. To test this hypothesis, we examined the predictive role of various fat deposits including mesenteric fat thickness, and various metabolic variables on the risk of fatty liver. SUBJECTS AND METHODS: A total of 291 Chinese subjects (134 men and 157 women with a mean BMI of 23.7 kg/m2, range: 16.5-33.4 kg/m2) underwent ultrasound examination for measurement of mesenteric, subcutaneous and preperitoneal fat thickness, and for diagnosis of fatty liver. Body mass index, waist circumference, and waist-hip ratio were recorded. Blood pressure was measured. Fasting plasma glucose, insulin resistance, high-density lipoprotein cholesterol (HDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), liver enzymes were determined by common methods. RESULTS: The subjects with fatty liver had greater abdominal fat thickness and higher anthropometric indexes than those without fatty liver. The subjects with fatty liver also showed higher blood pressure, worse lipid and glycaemic profile compared with those without fatty liver. Using multiple logistic regression analysis, mesenteric fat thickness was a risk factor of fatty liver, independent of body mass index, age, sex, insulin resistance, fasting plasma glucose, lipid and blood pressure. The odds ratio was 1.5 (95% confidence interval: 1.27-1.77) for every 1 mm increase in the mesenteric fat thickness. Measurement of preperitoneal and subcutaneous fat deposits did not show significant associations with fatty liver. CONCLUSION: Mesenteric fat thickness measured on ultrasound is an independent determinant of fatty liver.

Abdominal Fat↗
PubMed1988

Enzyme histochemical and ultrastructural approach in orotic acid-induced fatty liver and their recovery process in Wistar rats.

Fatty liver was induced in Wistar rats by orotic acid and the recovery process was studied by enzyme histochemical staining for non specific esterase, lipase and by ultrastructural investigation. Enzyme histochemically, these enzyme activities were markedly decreased in orotic acid-induced fatty liver. However, during the recovery process after the end of orotic acid administration, these enzyme activities clearly appeared. Under these conditions, no significant ultrastructural alterations could be detected. Based on our data, pathogenesis of orotic acid-induced fatty liver was discussed.

Animals↗
PubMed1999

Relationship between serum leptin and fatty liver in Japanese male adolescent university students.

OBJECTIVE: The aim of this study was to elucidate the relationship between serum leptin levels and fatty liver in male adolescents. METHODS: We investigated the relationship between the concentration of circulating leptin and fatty liver by measuring the serum concentration of leptin in 284 male students who received the matriculation health examination in Okayama University in 1996 (n = 197; age, 18-20 yr) or 1997 (n = 87; age, 18-20 yr). RESULTS: Serum leptin levels correlated positively with body mass index (BMI), percent body fat (%FAT), thickness of skin fold (TSF), and serum concentration of ALT in 197 subjects. Examination of serum leptin in 67 subjects with BMI > or = 24.2 but < 28.6 kg/m2 showed a progressively higher levels in subjects with high serum ALT. Serum leptin levels in subjects with abnormally high serum ALT (> or = 37 IU/L) were significantly higher (p < 0.05) than in subjects with normal serum ALT, independent of BMI, %FAT, and TSF. Serum leptin levels were also significantly higher in subjects with fatty liver (detected by abdominal ultrasonography), independent of BMI and %FAT, compared with subjects without fatty liver. Stepwise multiple regression analysis showed that serum leptin level was an independent risk factor for fatty liver. In addition, serum leptin levels correlated with serum ALT (r = 0.518; p < 0.0005) and cholinesterase (r = 0.511; p < 0.0005) levels in 48 subjects with fatty liver. CONCLUSIONS: Our results demonstrated that serum leptin concentrations are high in male adolescents with simple obesity and are associated with high serum ALT or fatty liver, independent of BMI and %FAT, suggesting that the concentration of circulating leptin correlates with fatty liver caused by accumulation of visceral fat.

Adipose Tissue↗
PubMed1997

Decreased serum lecithin:cholesterol acyltransferase activity in spontaneous cases of fatty liver in cows.

Lecithin:cholesterol acyltransferase (LCAT) activity in serum was evaluated in spontaneous cases of fatty liver in cows. The enzyme activity of 631 +/- 62 U (mean +/- SEM, decrease in nmol of free cholesterol per h per ml of serum) in cows with fatty liver (n = 16) was significantly (p < 0.01) lower than that in cows without fatty liver (979 +/- 22 U; n = 16). In addition to the decrease in LCAT activity, the concentrations of phosphatidylcholine (a fatty aryl donor for esterification of free cholesterol) and of cholesteryl esters (products of the LCAT reaction) were reduced in the high-density lipoprotein fractions from cows with fatty livers. The concentrations in the serum of apolipoprotein A-I, an activator of LCAT, was also reduced in cows with fatty livers. These results suggest that the decreased LCAT activity, which may be attributable to impaired hepatic secretion or to the suppression of the activity in the plasma by reduced concentrations of phosphatidylcholine and apolipoprotein A-I, resulted in the lower concentrations of cholesteryl esters. Because cholesteryl esters are utilized in steroidogenic tissues for the synthesis of steroid hormones such as progesterone and glucocorticoids, and insufficient supply of the cholesterols may be of relevance to the reduced fertility and immune competence observed in cows with fatty livers.

Animals↗
PubMed1994

Modulation of mitogenesis by liver fatty acid binding protein.

Liver fatty acid binding protein (L-FABP), a cytoplasmic 14 kDa protein previously termed Z protein, is conventionally considered to be an intracellular carrier of fatty acids in rat hepatocytes. The following evidence now indicates that L-FABP is also a specific mediator of mitogenesis of rat hepatocytes: a. the synergy between the action of L-FABP and unsaturated fatty acids, especially linoleic acid, in the promotion of cell proliferation; b. the specific requirement for L-FABP in induction of mitogenesis by two classes of nongenotoxic hepatocarcinogenic peroxisome proliferators (amphipathic carboxylates and tetrazole-substituted acetophenones); c. the direct correlation between the binding avidities of different prostaglandins for L-FABP and their relative growth inhibitory activities toward cultured rat hepatocytes; d. the temporal coincidences between the covalent binding to L-FABP by chemically reactive metabolites of the genotoxic carcinogens, 2-acetylaminofluorene and aminoazo dyes, and their growth inhibitions of hepatocytes during liver carcinogenesis in rats; e. and f. the marked elevations of L-FABP in rat liver during mitosis in normal and regenerating hepatocytes, and during the entire cell cycle in the hyperplastic and malignant hepatocytes that are produced by the genotoxic carcinogens, 2-acetylaminofluorene and aminoazo dyes. These actions of L-FABP are consistent with those of a protein involved in regulation of hepatocyte multiplication. Discovery that L-FABP, the target protein of the two types of genotoxic carcinogens, is required for the mitogenesis induced by two classes of nongenotoxic carcinogens points to a common process by which both groups of carcinogens promote hepatocyte multiplication. The implication is that during tumor promotion of liver carcinogenesis, these genotoxic and nongenotoxic carcinogens modify the normal process by which L-FABP, functioning as a specific receptor of unsaturated fatty acids or their metabolites, promotes the multiplication of hepatocytes.

Animals↗
PubMed2006

[Association of hepatic iron deposition and serum iron indices with hepatic inflammation and fibrosis stage in nonalcoholic fatty liver disease].

BACKGROUND/AIMS: Nonalcoholic steatohepatitis can develop from nonalcoholic fatty liver and progress to severe liver disease such as cirrhosis. The mechanism determining the progression from fatty liver to steatohepatitis is unknown. Iron is suspected to enhance hepatic damage associated with nonalcoholic fatty liver disease (NAFLD). The aims of this study were to evaluate the relationship of serum iron indices and hepatic iron deposition with hepatic fibrosis or inflammation, and to assess whether the increased hepatic iron deposition is an independent predictor of progression to liver injury. METHODS: The biochemical and histopathological data of thirty-nine patients with NAFLD were analyzed. Liver biopsy findings were graded according to the method described by Brunt, et al. Hepatic iron concentration was available in 29 of 39 patients. RESULTS: The mean hepatic iron concentration and hepatic iron indices were 1,349+/-1,188 microg/g dry weight and 0.9+/-0.7 microg/g/age. Serum ferritin and body mass indices were associated with hepatic inflammation (p=0.001, p=0.006) and fibrosis (p=0.005, p=0.013). Hepatic iron concentration and hepatic iron index were not associated with hepatic inflammation and fibrosis. Multivariate analysis did not identify serum ferritin or body mass index as an independent predictor of liver injury. CONCLUSIONS: Hepatic iron deposition shows no association with the degree of hepatic inflammation or fibrosis. Hepatic iron is not an independent predictor of hepatic injury in patients with NAFLD.

Adolescent↗
PubMed2004

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.

BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Fatty Liver↗
PubMed2001

Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status.

Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F(0)F(1)-ATP synthase content, tissue ATP concentration, and liver histology were also determined. Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta-F(1) subunit of the F(0)F(1)-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. In the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta-F(1) subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F(0)F(1)-ATP synthase. These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.

ATP Synthetase Complexes↗
PubMed1994

Reduced protein kinase C activity and endogenous protein phosphorylation in ethionine-induced fatty liver in cows.

Protein kinase C (PKC) activity was evaluated and the phosphorylation of its endogenous substrates was explored in fatty liver induced by administration of ethionine (an analogue of methionine) to cows in order to assess the relevance of PKC-dependent phosphorylation in the development of fatty liver. PKC activity was decreased in both the cytosolic and the total particulate fractions from fatty livers, compared to the corresponding fractions from control liver. The mode of activation by the PKC cofactors (1-oleoyl-2-acetyl-sn-glycerol, 12-O-tetradecanoylphorbol-13-acetate, phosphatidyl-serine and Ca2+) was similar in both control and fatty livers, suggesting a quantitative but not a qualitative change in PKC in fatty liver. At least three substrate proteins (34 kDa, 26 kDa and 19 kDa) were found in the cytosolic fraction and their phosphorylation was reduced in fatty liver. These results suggest that impairment of the signal transduction pathway mediated by PKC is involved in the pathogenesis of fatty liver in cows.

Animals↗