Sex Difference in Induction of Fatty Liver in the Rat by Dietary Orotic Acid

Sidransky, Herschel

doi:10.1210/endo-72-5-709

Cited by 15 publications

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“…Sucroselorotic acid diet.-Fatty liver without serowas induced in female Sprague-Dawley rats ( n = 109; weight, 200-250 g) by feeding an adenine-deficient sucrose diet containing 1% orotic acid (OA) for 2-3 weeks (26)(27)(28)(29)(30). This diet consisted of 60% sucrose, 20% casein hydrolysate, 10% cellulose, 4% corn oil, 3.5% minerals, 1.5% vitamins, and 1% OA (ICN Biochemicals, Cleveland).…”

Section: Fatty Liver M O D E L S Logic and Histologic Evidence Of Hepmentioning

confidence: 99%

“…To assess the relative advantages of these diverse MR imaging methods in the diagnosis of fatty liver, we correlated serologic, biochemical, and histologic findings in experimental models of fatty liver with quantitative data derived from relaxometry, conventional and chemical shift MR imaging, and contrast-enhanced MR imaging. weight, 200-250 g) by feeding an adenine-deficient sucrose diet containing 1% orotic acid (OA) for 2-3 weeks (26)(27)(28)(29)(30). This diet consisted of 60% sucrose, 20% casein hydrolysate, 10% cellulose, 4% corn oil, 3.5% minerals, 1.5% vitamins, and 1% OA (ICN Biochemicals, Cleveland).…”

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Diagnosis of fatty liver with MR imaging

Kreft

Tanimoto

Baba

et al. 1992

Magnetic Resonance Imaging

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The diagnosis of fatty liver with magnetic resonance (MR) imaging was evaluated in experimental rat models of simple fatty infiltration and fatty liver with hepatocellular injury. T1 and T2 were measured ex vivo and correlated with the histologic degree of fatty infiltration. Enhancement of fatty liver with four different cells-specific contrast agents was studied with ex vivo relaxometry and in vivo MR imaging. Quantitative analysis of conventional and chemical shift MR images was correlated with biochemically determined fat content of the liver. Diet-induced simple fatty infiltration of the liver caused a decrease in T1 of 15%, whereas the T1 of L-ethionine-induced fatty liver with hepatocellular injury increased by 12%. T2 showed a positive correlation with the degree of fatty infiltration in both models. Cell-specific hepatobiliary contrast agents showed the same liver uptake and relaxation enhancement in fatty livers as in normal livers. Conventional T1-weighted images and chemical shift images showed good correlation (r = .83 and .80, respectively) between signal intensity and the degree of fatty infiltration. However, only chemical shift imaging was reliable in the diagnosis of fatty liver.

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Section: Fatty Liver M O D E L S Logic and Histologic Evidence Of Hepmentioning

confidence: 99%

mentioning

confidence: 99%

Diagnosis of fatty liver with MR imaging

Kreft

Tanimoto

Baba

et al. 1992

Magnetic Resonance Imaging

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“…The fatty liver we are describing was produced in theff rats by dietary means. The diet is a semisynthetic diet to which we added 1% orotic acid to produce a fatty liver in Holtzman-Sprague-Dawley rats (3)(4)(5)(6)(7) and to study the effects of the hypolipidemic agent ethyl pchlorophenoxyisobutyrate (clofibrate) (8). The diet contains 60% sucrose, wt/wt, and it will be referred to as the "experimental diet."…”

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confidence: 99%

Fatty liver induced in Zucker "fatty" (ff) rats by a semisynthetic diet rich in sucrose.

Novikoff¹

1977

Proc. Natl. Acad. Sci. U.S.A.

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A new fatty liver model is described in which heredity plays a major role. A marked fatty liver develo s when the homozygous mutant Zucker rat (ff or "fatty") is fe a semisynthetic diet enriched in sucrose. Lean littermates do not develop fatty livers on this experimental diet. Even old ff rats do not develop fatty livers on chow; the experimental diet is required. The fatty liver is described, including light microscopic and preliminary electron microscopic observations. The clinical importance of understanding the pathogenesis of fatty liver is obvious, and a variety of animal models have been intensively studied. In the new model described here, genetic constitution exerts a major influence. We have induced a fatty liver in a mutant rat widely used in studies of obesity since 1961, when Zucker and Zucker reported that its obesity is inherited as an autosomal Mendelian recessive trait (1). Much is known about hormonal imbalances and lipogenesis in the Zucker rat (ff or "fatty"); these features have been reviewed most recently by Bray, who compared this type of obesity with a hypothalamic model of obesity (2). In contrast, little is known about the livers of Zucker rats, either lean or ff, and we have been unable to find reports on either their light microscopic histology or their ultrastructure.The ff rats develop enormous numbers of large adipocytes but their livers do not become fatty. The fatty liver we are describing was produced in theff rats by dietary means. The diet is a semisynthetic diet to which we added 1% orotic acid to produce a fatty liver in Holtzman-Sprague-Dawley rats (3-7) and to study the effects of the hypolipidemic agent ethyl pchlorophenoxyisobutyrate (clofibrate) (8). The diet contains 60% sucrose, wt/wt, and it will be referred to as the "experimental diet." This diet was recognized by Shiff et al. (9) as Abbreviations: ATPase, adenosine triphosphatase; ER, endoplasmic reticulum; VLDL, very low density lipoprotein.producing a hyperlipidemia in Holtzman-Sprague-Dawley rats. More recently, we used the same diet in studies demonstrating: (a) that clofibrate will neutralize the orotic acid effect if fed simultaneously with the orotic acid (10); and (b) that a clofibrate + orotic acid diet will reverse an already established orotic acid-induced fatty liver (11). I was interested in studying the effects of the hyperlipidemia-inducing semisynthetic diet on the liver of a rat with congenital hyperlipidemia. This led to the development of the fatty liver model described here. MATERIALS AND METHODSThe Zucker rats were purchased from Harriet G. Bird Memorial Laboratory, Stow, MA. A total of 6 ff and 8 lean littermate rats, 2-4 months of age and of both sexes, were fed on Purina rat chow. Five ff and 7 lean littermate rats, of the same age and of both sexes, were fed the experimental diet, for 1 week or 3 weeks. As additional controls, four 7-month-old fatties and 4 littermate leans maintained on chow were studied.The experimental diet consisted of 60% sucrose, 20% vitamin-free casein, 4...

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“…The fatty liver we are describing was produced in theff rats by dietary means. The diet is a semisynthetic diet to which we added 1% orotic acid to produce a fatty liver in Holtzman-Sprague-Dawley rats (3)(4)(5)(6)(7) and to study the. effects of the hypolipidemic agent ethyl pchlorophenoxyisobutyrate (clofibrate) (8).…”

mentioning

confidence: 99%

Fatty liver induced in Zucker "fatty" (ff) rats by a semisynthetic diet rich in sucrose.

Novikoff¹

1977

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A new fatty liver model is described in which heredity plays a major role. A marked fatty liver develops when the homoz gous mutant Zucker rat (ff or "fatty") is fe a semisynthetic Jiet enriched in sucrose. Lean littermates do not develop fatty livers on this experimental diet. Even old ff rats do not develop fatty livers on chow; the experimental diet is required. The fatty liver is described, including light microscopic and preliminary electron microscopic observations. The clinical importance of understanding the pathogenesis of fatty liver is obvious, and a variety of animal models have been intensively studied. In the new model described here, genetic constitution exerts a major influence. We have induced a fatty liver in a mutant rat widely used in studies of obesity since 1961, when Zucker and Zucker reported that its obesity is inherited as an autosomal Mendelian recessive trait (1). Much is known about hormonal imbalances and lipogenesis in the Zucker rat (ff or "fatty"); these features have been reviewed most recently by Bray, who compared this type of obesity with a hypothalamic model of obesity (2). In contrast, little is known about the livers of Zucker rats, either lean or ff, and we have been unable to find reports on either their light microscopic histology or their ultrastructure.The ff rats develop enormous numbers of large adipocytes but their livers do not become fatty. The fatty liver we are describing was produced in theff rats by dietary means. The diet is a semisynthetic diet to which we added 1% orotic acid to produce a fatty liver in Holtzman-Sprague-Dawley rats (3-7) and to study the. effects of the hypolipidemic agent ethyl pchlorophenoxyisobutyrate (clofibrate) (8). The diet contains 60% sucrose, wt/wt, and it will be referred to as the "experimental diet." This diet was recognized by Shiff et al. (9) as Abbreviations: ATPase, adenosine triphosphatase; ER, endoplasmic reticulum; VLDL, very low density lipoprotein.producing a hyperlipidemia in Holtzman-Sprague-Dawley rats. More recently, we used the same diet in studies demonstrating: (a) that clofibrate will neutralize the orotic acid effect if fed simultaneously with the orotic acid (10); and (b) that a clofibrate + orotic acid diet will reverse an already established orotic acid-induced fatty liver (11). I was interested in studying the effects of the hyperlipidemia-inducing semisynthetic diet on the liver of a rat with congenital hyperlipidemia. This led to the development of the fatty liver model described here. MATERIALS AND METHODSThe Zucker rats were purchased from Harriet G. Bird Memorial Laboratory, Stow, MA. A total of 6 ff and 8 lean littermate rats, 2-4 months of age and of both sexes, were fed on Purina rat chow. Five ff and 7 lean littermate rats, of the same age and of both sexes, were fed the experimental diet, for 1 week or 3 weeks. As additional controls, four 7-month-old fatties and 4 littermate leans maintained on chow were studied.The experimental diet consisted of 60% sucrose, 20% vitamin-free casein, 4...

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Sex Difference in Induction of Fatty Liver in the Rat by Dietary Orotic Acid

Cited by 15 publications

References 0 publications

Diagnosis of fatty liver with MR imaging

Diagnosis of fatty liver with MR imaging

Fatty liver induced in Zucker "fatty" (ff) rats by a semisynthetic diet rich in sucrose.

Fatty liver induced in Zucker "fatty" (ff) rats by a semisynthetic diet rich in sucrose.

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