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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arginine deficiency is known to lead to marked alterations in pyrimidine biosynthesis and the excessive loss of urinary orotic acid. Orotic acid feeding is known to lead to hepatic steatosis. These studies show that arginine deficiency also results in a marked increase in liver lipids in the rat. The majority of the increased liver lipid can be accounted for by triglyceride accumulation. Increased liver lipid infiltration was found to be independent of the sex of the rat. Accompanying this increase was a decrease in serum triglycerides and cholesterol concentrations. Fatty infiltrations induced by arginine deficiency could be reversed by refeeding an arginine enriched diet. Adenine supplementation (0.30%) to the arginine deficient diet also completely prevented the induction of fatty livers. Adenine supplementation resulted in a dramatic increase in urinary orotic acid excretion in the arginine deficient rat. Guanine supplementation (0.5%) to an arginine deficient diet reduced but did not prevent the induction of fatty livers. The similarities of fatty livers induced by arginine deficiency and orotic acid feeding are discussed.
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PMID:Mechanism for fatty liver induction in rats fed arginine deficient diets. 43 Feb 66

Weanling male Sprague-Dawley rats were fed ad libitum 15% casein diets with and without 5.0% lysine-HCI, 0.25% adenine sulfate or 0.1% allopurinol for 2 weeks. Addition of lysine alone depressed 2-week growth from 94 to 65 g increased average daily urinary orotic acid excretion from 0.39 to 1.77 mg and increased the percentage of total liver lipids from 3.6 to 11.2. Adenine or allopurinol did not change growth but markedly enhanced lysine-induced orotic aciduria and completely prevented lysine-induced fatty livers. Reports by other show that adenine and allopurinol also prevent fatty livers or rats fed arginine-free diets or excess orotic acid. The authors conclude that lysine-induced orotic aciduria results from arginine deficiency caused by antagonism of arginine function by lysine, and that lysine-induced fatty liver probably results from a lesion identical to that produced by feeding excess orotic acid.
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PMID:Fatty liver of growing rats fed excess lysine and its prevention by adenine or allopurinol. 678 27

Neonatal hepatic steatosis (OMIM 228100) is a fatal condition of unknown etiology characterized by a pale and yellow liver and early postnatal mortality. In the present study, a deficit in adenosine-dependent metabolism is proposed as a causative factor. Physiologically, adenosine is efficiently metabolized to AMP by adenosine kinase (ADK), an enzyme highly expressed in liver. ADK not only ensures normal adenine nucleotide levels but also is essential for maintaining S-adenosylmethionine-dependent transmethylation processes, where adenosine, an obligatory product, has to be constantly removed. Homozygous Adk(-/-) mutants developed normally during embryogenesis. However, within 4 days after birth they displayed microvesicular hepatic steatosis and died within 14 days with fatty liver. Adenine nucleotides were decreased and S-adenosylhomocysteine, a potent inhibitor of transmethylation reactions, was increased in the mutant liver. Thus, a deficiency in adenosine metabolism is identified as a powerful contributor to the development of neonatal hepatic steatosis, providing a model for the rapid development of postnatally lethal fatty liver.
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PMID:Neonatal hepatic steatosis by disruption of the adenosine kinase gene. 1199 62

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet. Protection against fatty liver is partially recapitulated by the systemic administration of low-dose carboxyatractyloside, a specific inhibitor of ANT. Targeted manipulation of hepatic mitochondrial metabolism, particularly through inhibition of ANT, may represent an alternative approach in NAFLD and obesity treatment.
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PMID:Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance. 3130 76