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)

Fatty liver has been anecdotally associated with heterozygous hypobetalipoproteinemia. The aim of this study was to characterize the molecular defect in a subject with heterozygous hypobetalipoproteinemia (low-density lipoprotein cholesterol, 52 mg/dL; apolipoprotein [apo] B, 15 mg/dL) and otherwise unexplained fatty liver. Plasma lipoproteins were separated by ultracentrifugation, and apo B was analyzed by electrophoresis and immunoblotting. A fragment of genomic DNA corresponding to the 5' end of exon 26 of the apo B gene was amplified by polymerase chain reaction and sequenced. The plasma lipoproteins of the proband contained, besides normal apo B-100, a 200-kilodalton truncated apo B whose size suggested the presence of a mutation in exon 26 of the apo B gene. The nucleotide sequence of a fragment of the 5' end of exon 26 revealed that the proband was a heterozygote for a 14-nucleotide deletion, producing a frameshift resulting in a premature stop codon at residue 1768. This truncated apo B was named apo B-38.95. The proband's father was a carrier of the same mutation. Fatty liver in this subject with familial heterozygous hypobetalipoproteinemia most likely results from the inability of apo B-38.95 to export lipids from hepatocytes into the blood stream. Heterozygous hypobetalipoproteinemia should be considered in a hypolipidemic subject with an otherwise unexplained fatty liver.
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PMID:Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. 883 9

Deficiency of apolipoprotein can be of genetic origin or due to diseases like advanced chronic liver disease. Deficiency of apolipoprotein A causes Tangier disease without any major hepatic involvement being reported. Deficiency of apolipoprotein B causes abetalipoproteinemia or familial hypobetalipoproteinemia; with hepatic involvement in the form of raised transaminases, fatty liver and cirrhosis. Advanced chronic liver disease itself can cause reduction of apolipoprotein A and apolipoprotein B levels and acanthocytosis. In patients with chronic liver disease of undetermined etiology, lipid profile and apolipoprotein levels should be obtained routinely. If it suggests apolipoprotein B deficiency, then liver biopsy can be avoided, as the etiology of chronic liver disease is established. Isolated deficiency of either apolipoprotein A or apolipoprotein B suggests etiology of chronic liver disease, while deficiency of both apolipoprotein A and apolipoprotein B is a manifestation of advanced chronic liver disease.
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PMID:Apolipoprotein deficiency and chronic liver disease. 1122 45

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.
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PMID:Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene. 1159 Feb 10

Reduced feed intake near parturition is suggested to be one of the major causal factors for the development of fatty liver in cows, and nonfeeding has been used as an experimental model for fatty liver. In cows with fatty liver, concentrations of lipoprotein lipids and proteins are decreased. In addition, the acute-phase protein haptoglobin is induced. The purpose of the present study was to examine whether the decrease of lipoprotein concentrations and the induction of acute-phase proteins were similarly reproduced by non-feeding. Holstein female calves (n=5) were nonfed for 3 days and thereafter refed. Serum concentrations of nonesterified fatty acids and beta-hydroxybutyric acid were initially increased by the nonfeeding, and followed by decreases in concentrations of cholesteryl esters, phospholipids, apolipoprotein (apo) B-100 and apoA-I. The apoC-III concentration was not distinctly decreased. Haptoglobin and serum amyloid A were induced during the nonfeeding and refeeding process. Haptoglobin was distributed in different proportions in the high-density lipoprotein, very high-density lipoprotein and the lipoprotein-deficient fractions, whereas almost all serum amyloid A was associated with the high-density lipoprotein fraction. These results suggest that the decreases in lipoprotein concentrations and induction of acute-phase proteins found in cows with fatty liver and those with fatty liver-related diseases such as ketosis are primarily due to the reduced feed intake near parturition.
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PMID:Decreases of apolipoprotein B-100 and A-I concentrations and induction of haptoglobin and serum amyloid A in nonfed calves. 1185 46

Milk fever occurring during the peripartum period has been suggested to be caused by fatty liver developed during the non-lactating stage because diseased cows have increased serum concentrations of non-esterified fatty acids (NEFA) and show hepatic lipidosis. In cows with fatty liver and related diseases such as ketosis, serum concentrations of apolipoprotein (apo) B-100 and apoA-I are decreased. The purpose of the present study was to examine whether apoB-100 and apoA-I concentrations are similarly decreased in cows with milk fever. Apolipoprotein concentrations were also measured in cows with downer syndrome, which has been suggested to be related, at least in part, to milk fever. Compared with healthy cows during early lactation, apoB-100 and apoA-I concentrations were decreased in cows with milk fever and also in downer cows. In cows with milk fever, the decreases in apoB-100 and apoA-I concentrations were associated with increased NEFA and decreased cholesterol and phospholipid concentrations. However, in downer cows, serum lipid concentration changes were not as distinct as in cows with milk fever. These results, coupled with previous findings on the decreases in apoB-100 and apoA-I concentrations of cows with fatty liver-related diseases, suggest that fatty liver is involved in the development of milk fever and partly in that of downer cow syndrome.
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PMID:Decreases in serum apolipoprotein B-100 and A-I concentrations in cows with milk fever and downer cows. 1185 46

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

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

Type 2 diabetes in humans is associated with increased de novo lipogenesis (DNL), increased fatty acid (FA) fluxes, decreased FA oxidation, and hepatic steatosis. In this condition, VLDL production is increased and resistant to suppressive effects of insulin. The relationships between hepatic FA metabolism, steatosis, and VLDL production are incompletely understood. We investigated VLDL-triglyceride and -apolipoprotein (apo)-B production in relation to DNL and insulin sensitivity in female ob/ob mice. Hepatic triglyceride (5-fold) and cholesteryl ester (15-fold) contents were increased in ob/ob mice compared with lean controls. Hepatic DNL was increased approximately 10-fold in ob/ob mice, whereas hepatic cholesterol synthesis was not affected. Basal rates of hepatic VLDL-triglyceride and -apoB100 production were similar between the groups. Hyperinsulinemic clamping reduced VLDL-triglyceride and -apoB100 production rates by approximately 60% and approximately 75%, respectively, in lean mice but only by approximately 20% and approximately 20%, respectively, in ob/ob mice. No differences in hepatic expression of genes encoding apoB and microsomal triglyceride transfer protein were found. Hepatic expression and protein phosphorylation of insulin receptor and insulin receptor substrate isoforms were reduced in ob/ob mice. Thus, strongly induced hepatic DNL is not associated with increased VLDL production in ob/ob mice, possibly related to differential hepatic zonation of apoB synthesis (periportal) and lipid accumulation (perivenous) and/or relatively low rates of cholesterogenesis. Insulin is unable to effectively suppress VLDL-triglyceride production in ob/ob mice, presumably because of impaired insulin signaling.
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PMID:Hepatic VLDL production in ob/ob mice is not stimulated by massive de novo lipogenesis but is less sensitive to the suppressive effects of insulin. 1271 36

Familial hypobetalipoproteinemia (FHBL) is a rare codominant disorder of lipoprotein metabolism characterized by low levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. Heterozygotes for FHBL have less-than-half normal LDL-cholesterol and apoB concentrations, whereas homozygotes have extremely low or undetectable LDL-cholesterol and apoB levels. These reductions in LDL-cholesterol and apoB have been suggested to provide FHBL subjects with resistance to atherosclerosis. FHBL can be caused by mutations in the APOB gene on chromosome 2. We present four novel mutations and one previously described mutation in APOB causing FHBL in five families. Immunoblotting and DNA sequencing were used to characterize the novel mutation apoB-40.3 (c.5564_5565insC) and the previously reported mutation apoB-80.5 (c.11040T>G). The apoB-6.9 (c.1018_1025del) and apoB-25.8 (c.3600T>A) mutations were identified by DNA sequence analysis, as variants shorter than apoB-31 are not detectable in plasma. A fifth mutation, the splice variant c.82+1G>A, was identified by sequencing and was found in a homozygous subject. In approximately 50% of the FHBL subjects, plasma alanine aminotransferase concentrations were mildly increased, suggestive of fatty liver. All affected FHBL subjects had low to low-normal serum vitamin E concentrations, highlighting the important and recognized relationship between lipid and vitamin E concentrations.
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PMID:Four novel mutations in APOB causing heterozygous and homozygous familial hypobetalipoproteinemia. 1287 64

The unique inborn hypertriglyceridemia seen in FLS (fatty liver Shionogi) mice was relieved by the administration of purified apolipoprotein (apo) C-II. Lipoprotein lipase (LPL) and its cofactor, apoC-II, play a pivotal role in VLDL metabolism. Therefore, we investigated the genetic background involved in this hypertriglyceridemia. Plasma levels of TG and total cholesterol as well as LPL activity were measured in male FLS mice and C57/BL6J mice. Agarose gel electrophoresis and fast protein liquid chromatography were used to analyze the lipoprotein profile. A cross experiment was done to determine the genetic background of hypertriglyceridemia observed in FLS mice. cDNA sequences of apoC-II and apoC-III of FLS mice were determined. Prealpha-lipoprotein was the predominant lipoprotein class in FLS mouse plasma. LPL activity remained in the range observed in C57/BL6J mice, and purified apoC-II transiently relieved FLS mice from hypertriglyceridemia. Prealpha-lipoproteinemia was inherited in an autosomal recessive manner. ApoC-III appeared to be a causal factor for this unique hypertriglyceridemia. Microsatellite analysis, however, revealed that the responsible chromosome was not 7; rather, apoC-III mapped onto chromosome 9. Therefore, we suggest apoC-III as a candidate causative factor for the hypertriglyceridemia observed in FLS mice because an excessive amount of apoC-III attenuates LPL activity in vivo and in vitro.
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PMID:A novel type hypertriglyceridemia observed in FLS mice. 1450 31


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