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

Most metabolic diseases in dairy cows occur during the peripartum period and are suggested to be derived from fatty liver initially developed during the nonlactating stage. Fatty liver is induced by hepatic uptake of nonesterified fatty acids that are released in excess by adipose tissues attributable to negative energy balance. The fatty accumulation leads to impairment of lipoprotein metabolism in the liver, and the impairment in turn influences other metabolic pathways in extrahepatic tissues such as the steroid hormone production by the corpus luteum. Detailed understanding of the impaired lipoprotein metabolism is crucial for elucidation of the mechanistic bases of the development of fatty liver and fatty liver-related peripartum diseases. This review summarizes results on evaluation of lipoprotein lipid and protein concentrations and enzyme activity in cows with fatty liver and those with ketosis, left displacement of the abomasum, milk fever, downer syndrome and retained placenta. Obtained data strongly suggest that decreases in serum concentrations of apolipoprotein B-100, apolipoprotein A-I and apolipoprotein C-III, a reduction in activity of lecithin:cholesterol acyltransferase and induction of haptoglobin and serum amyloid A are intimately related to the development of fatty liver and fatty liver-related diseases. Moreover, determination of the apolipoprotein concentrations and enzyme activity during the peripartum period is useful for early diagnoses of these diseases.
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PMID:Relevance of apolipoproteins in the development of fatty liver and fatty liver-related peripartum diseases in dairy cows. 1201 73

Previous reports have shown that the liver-type glucose transporter GLUT2 gene expression is upregulated in the liver of obese and diabetic animals and in human subjects. This phenomenon is correlated with an increased glucose output from the liver; however, the regulatory mechanism is not clear. To investigate the relationship between hepatic steatosis, frequently found in obese and diabetic patients, and GLUT2 gene expression, we developed an oleic acid-induced in vitro fatty liver model. Lipid-accumulated cells morphologically mimicking hepatic steatosis were successfully induced in the human HepG2 cell line by 24-h culture with oleic acid at 1 mM. The cells with steatosis showed increased levels of intracellular triglycerides and apolipoprotein B, which were reduced in the presence of bezafibrate at 100 &mgr;g/ml. GLUT2 mRNA expression estimated by semi-quantitative reverse transcription polymerase chain reaction was increased in the cells with steatosis. Bezafibrate inhibited GLUT2 mRNA expression in the cells with and without steatosis. These results suggest that hepatic steatosis causes the enhancement of hepatic GLUT2 mRNA expression, which may be associated with gluconeogenesis and insulin resistance.
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PMID:Enhanced GLUT2 gene expression in an oleic acid-induced in vitro fatty liver model. 1204 68

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 +/- 11.5 and 3.3 +/- 2.9 (mean +/- SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar degrees of obesity, FHBL subjects have more hepatic fat. VLDL-triglyceride (TG)-fatty acids arise from plasma and nonplasma sources (liver and splanchnic tissues). To assess the relative contributions of each, [2H2]palmitate was infused over 12 h in 13 FHBL subjects and 11 controls. Isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry. Non-plasma sources contributed 51 +/- 15% in FHBL and 37 +/- 13% in controls (P = 0.02). Correlations of liver fat percentage and percent VLDL-TG-palmitate from liver were r = 0.89 (P = 0.0001) for FHBL subjects and r = 0.69 (P = 0.01) for controls. Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG.
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PMID:Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis. 1256 73

Hepatitis C virus (HCV) infection is associated with the development of steatosis in the liver. Recently, infection with genotype 3a HCV has been reported to have a closer association with hepatic steatosis than that with genotype 1 or 2 HCV. Moreover, infection with genotype 3a HCV but not with genotype 1 has been shown to be associated with serum hypocholesterolemia or hypobetalipoproteinemia in European countries. We conducted a case control study to characterize the serum lipid profile in patients infected with genotype 1b HCV, which is the most prevalent HCV genotype in Japan. These patients had significantly lower serum cholesterol levels than those infected with HBV or genotype 2a HCV who had similar liver disease progression and body mass index. Further analysis of serum apolipoproteins revealed that not only apolipoprotein B but also apolipoprotein CII and apolipoprotein CIII levels were significantly reduced, while apolipoprotein AI, AII and E levels were similar in patients infected with genotype 1b HCV and those with HBV or genotype 2a HCV. These results indicate that, in Japan, infection with genotype 1b HCV is a cause of lipid metabolism disturbances, which may be associated with the pathogenesis of hepatitis C liver disease.
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PMID:Serum lipid profile of patients with genotype 1b hepatitis C viral infection in Japan. 1269 47

Elevation of transaminase levels in asymptomatic subjects could be due to a common benign condition such as fatty liver or a more serious disease such as chronic hepatitis due to various causes; in some subjects a liver biopsy is indicated. Heterozygous apolipoprotein B deficiency is an uncommon cause of transaminase elevation, as indicated by low levels of cholesterol and low density lipoprotein-cholesterol. This should be noted to avoid unnecessary investigations (including liver biopsy) in asymptomatic subjects with persistent elevation of transminase levels in the serum.
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PMID:Fatty liver with elevated transaminase levels due to heterozygous apolipoprotein B deficiency. 1297 15

Fatty liver is frequent in the apolipoprotein B (apoB)-defective genetic form of familial hypobetalipoproteinemia (FHBL), but interindividual variability in liver fat is large. To explain this, we assessed the roles of metabolic factors in 32 affected family members with apoB-defective FHBL and 33 related and unrelated normolipidemic controls matched for age, sex, and indices of adiposity. Two hour, 75 g oral glucose tests, with measurements of plasma glucose and insulin levels, body mass index, and waist-hip ratios were obtained. Abdominal subcutaneous, intraperitoneal (IPAT), and retroperitoneal adipose tissue masses were quantified by MR imaging, and hepatic fat was quantified by MR spectroscopy. Mean +/- SD liver fat percentage values of FHBL and controls were 14.8 +/- 12.0 and 5.2 +/- 5.9, respectively (P = 0.001). Means for these measures of obesity and insulin action were similar in the two groups. Important determinants of liver fat percentage were FHBL-affected status, IPAT, and area under the curve (AUC) insulin in both groups, but the strongest predictors were IPAT in FHBL (partial R(2) = 0.55, P < 0.0002) and AUC insulin in controls (partial R(2) = 0.59, P = 0.0001). Regression of liver fat percentage on IPAT fat was significantly greater for FHBL than for controls (P < 0.001). In summary, because apoB-defective FHBL imparts heightened susceptibility to liver triglyceride accumulation, increasing IPAT and insulin resistance exert greater liver fat-increasing effects in FHBL.
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PMID:Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity. 1496 20

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.
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PMID:[Hepatic steatosis associated with heterozygotic familial hypobetalipoproteinemia]. 1505 12

Limited secretion of very low density lipoproteins (VLDL) in dairy cows is strongly related to fatty liver and other metabolic disorders in the early postpartum. Currently, there is limited information on which roles apolipoprotein B(100) (ApoB(100)), apolipoprotein E (ApoE), and microsomal triglyceride transfer protein (MTP) play in that VLDL limitation. To our knowledge, no studies have simultaneously measured ApoB(100), ApoE, and MTP mRNA in periparturient dairy cows. Therefore, a trial was conducted to assess liver gene expression of these proteins in transition dairy cows and to evaluate the relationships between their expression and metabolic status. Eight multiparous Holstein cows were monitored during the transition period. To evaluate metabolic and nutritional status, body condition score was registered, and plasma indexes of energy metabolism and VLDL were determined from 35 d before to 35 d after calving. Liver biopsies were performed on d -35, 3, and 35 relative to day of calving, and gene expression of ApoB(100), ApoE, and MTP were determined on liver tissue. Body condition, plasma glucose and VLDL decreased, and plasma NEFA and BHBA increased after calving. Compared with values of d -35, on d 3 after calving the ApoB(100) mRNA synthesis was lower, whereas MTP and ApoE mRNA abundance were higher. Negative correlation (r = -0.57) between plasma NEFA concentration and ApoB(100) mRNA abundance, and positive correlation between ApoB(100) mRNA abundance and plasma cholesterol (r = 0.65) and plasma albumins (r = 0.52) were detected at 3 d postpartum. Data on changes of gene expression of the 3 main proteins involved in the regulation of synthesis and secretion of VLDL in the liver suggest that decreased mRNA for ApoB(100) may be consistent with decreased synthesis and/or secretion of VLDL from liver during the periparturient period.
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PMID:Abundance of mRNA of apolipoprotein b100, apolipoprotein e, and microsomal triglyceride transfer protein in liver from periparturient dairy cows. 1537 48

To monitor the serum concentration of apolipoprotein C-III (apoC-III), one of the functional apoproteins in lipid metabolism, in cows with ethionine-induced fatty liver, and to investigate the association of apoC-III with liver triglyceride (TG) content and serum biochemical variables, seven nonpregnant nonlactating Holstein cows (3 to 6 years old) were used. Five cows were treated with ethionine, an analogue of methionine, (days 0, 7 and 14). The remaining two controls received saline as the vehicle. Liver TG contents in the treated cows were increased markedly whenever administered, and significant increases were observed at days 14 (666.4%, 85.3 mg/g) and 21 (675.0%, 86.4 mg/g) compared with day 0. In controls, no significant changes in liver TG content and serum biochemical variables were observed during this experiment. The serum apoC-III concentration in the treated cows was decreased drastically after the first administration and fell to the lowest value at day 10 (76.2 microg/ml, 32% of day 0). The apoC-III was significantly (p<0.05) correlated with non-esterified fatty acids (r= -0.526), gamma-glutamyl transpeptidase (r= -0.407), total bilirubin (r= -0.464), positively with apolipoprotein B-100 (apoB-100, r=0.601) and cholesterol ester (r=0.449). Although apoB-100 concentrations were also reduced by the administrations, the concentrations tended to recover smoothly toward the next administration. The distinct difference in change between apoC-III and apoB-100 suggests that apoC-III may be regulated by other pathways, in addition to inhibiting the synthesis of apoproteins by ethionine.
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PMID:Decreases in serum apolipoprotein C-III concentration in cows with ethionine-induced fatty liver. 1547 76

Fatty liver is prevalent in apolipoprotein B (apoB)-defective familial hypobetalipoproteinemia (FHBL). Similar to humans, mouse models of FHBL produced by gene targeting (apob(+/38.9)) manifest low plasma cholesterol and increased hepatic triglycerides (TG) even on a chow diet due to impaired hepatic VLDL-TG secretive capacity. Because apoB truncations shorter than apoB48 are expressed in the intestine, we examined whether FHBL mice may have limited capacity for intestinal dietary TG absorption. In addition, we investigated whether FHBL mice are more susceptible to diet-induced hepatic TG accumulation. Fat absorption capacity was impaired in apoB38.9 mice in a gene dose-dependent manner. Relative fractional fat absorption coefficients for apob(+/+), apob(+/38.9), and apob(38.9/38.9) were 1.00, 0.96, and 0.71, respectively. To raise hepatic TG, we fed high-fat (HF) and low-fat (LF) pellets. Hepatic TG level was observed in rank order: HF > LF > chow. On both LF and HF, liver TG level was higher in the apob(+/38.9) than in apob(+/+). Hepatic TG secretion remained impaired in the apob(+/38.9) on the HF diet. Thus the FHBL mice are more susceptible to diet-induced fatty liver despite relatively reduced intestinal TG absorption capacity on a HF diet.
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PMID:Reduced intestinal fat absorptive capacity but enhanced susceptibility to diet-induced fatty liver in mice heterozygous for ApoB38.9 truncation. 1579 Jul 61


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