Isolated rat hepatocyte metabolism is affected by chronic renal failure

Cano, Noël; Catelloni, F.; Fontaine, Éric; Novaretti, R.; Costanzo-Dufetel, J. Di; Reynier, J; Leverve, Xavier

doi:10.1038/ki.1995.215

Cited by 23 publications

(10 citation statements)

References 39 publications

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“…1 H-NMR spectroscopy of liver tissue revealed that animals receiving the control diet already demonstrated significant changes in a broad range of metabolites at a relatively modest degree of uremia (Table 3) compared with unaffected animals on the same diet. Compounds involved in gluconeogenesis, ketogenesis, ureagenesis, and the citric acid cycle all demonstrated perturbations consistent with previous descriptions (3,5,7,24,33) of disturbed metabolism in uremia in both liver and nonhepatic tissues. Betaine supplementation had no effect on hepatic metabolism in unaffected animals, although there was a trend to higher hepatic betaine content that did not reach statistical significance.…”

Section: Resultssupporting

confidence: 90%

Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

Ogborn¹,

Nitschmann²,

Bankovic-Calic³

et al. 2000

American Journal of Physiology-Gastrointestinal and Liver Physi

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We undertook a morphometric and proton nuclear magnetic resonance ((1)H-NMR) study to test the hypothesis that 1% dietary betaine supplementation would ameliorate renal disease in the heterozygous Han:SPRD-cy rat, a model of polycystic kidney disease (PKD) and progressive chronic renal failure. After 8 wk of pair feeding, betaine had no effect on renal cystic change, renal interstitial fibrosis, serum creatinine, serum cholesterol, or serum triglycerides. (1)H-NMR spectroscopy of renal tissue revealed no change in renal osmolytes, including betaine, or renal content of other organic anions in response to diet. (1)H-NMR spectroscopy of hepatic tissue performed to explore the metabolic fate of ingested betaine revealed that heterozygous animals fed the control diet had elevated hepatic levels of gluconeogenic amino acids, increased beta-hydroxybutyrate, and increased levels of some citric acid cycle metabolites compared with animals without renal disease. Betaine supplementation eliminated these changes. Chronic renal failure in the Han:SPRD-cy rat is associated with disturbances of hepatic metabolism that can be corrected with betaine therapy, suggesting the presence of a reversible methylation defect in this form of chronic renal failure.

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Section: Resultssupporting

confidence: 90%

Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

Ogborn¹,

Nitschmann²,

Bankovic-Calic³

et al. 2000

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The physiological interpretation of this observation is not entirely clear. Klim et al (37) described increased urea production from alanine or glutamine in isolated hepatocytes from uremic rats, whereas Cano et al (16) reported decreased ureagenesis from these same substrates in isolated rat hepatocytes from their uremic animals (compared with controls in both cases). Even though the experimental designs differed, it is difficult to resolve the discrepancy between these results.…”

Section: R1584 Vampire Shrew Bear and Chronic Renal Failurementioning

confidence: 99%

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Singer

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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In the typical mammal, energy flux, protein metabolism, and renal excretory processes constitute a set of closely linked and quantitatively matched functions. However, this matching has limits, and these limits become apparent when animals adapt to unusual circumstances. The vampire bat and shrew have an extremely high protein intake, and the glomerular filtration rate (GFR) is not commensurate with the large urea load to be excreted. The vampire bat is chronically azotemic (blood urea concentration 27-57 mmol/l); yet there is no information as to how this animal has adjusted to such an azotemic internal environment. A high protein intake should also lead to chronic glomerular hyperfiltration; yet neither animal appears to develop progressive renal failure. The American black bear, on the other hand, has adapted to a prolonged period without intake or urine output. Despite continued amino acid catabolism with urea production, this mammal is able to completely salvage and reutilize urea nitrogen for protein synthesis, although the signals that initiate this metabolic adaptation are not known. The vampire bat, shrew, and bear are natural models adapted to circumstances analogous to chronic renal failure. Unraveling these adaptations could lead to new interventions for the prevention/treatment of chronic renal failure.

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“…The mechanism of this effect is still a matter of debate. Several authors [4,5] have suggested that it is due to a decrease in the efficiency of oxidative phosphorylation, whereas other results with isolated mitochondria did not support this conclusion [6,7]. Moreover, some studies have suggested that changes in oxidative phosphorylation in mitochondria from PUFA-deficient rats might be an artifact, resulting from damage sustained by the deficient mitochondria during their isolation [8,9], the waste of energy being linked to some other energy-consuming process such as transdermal water loss [3].…”

Section: Introductionmentioning

confidence: 99%

Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism

Piquet

Fontaine

Sibille

et al. 1996

Biochemical Journal

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The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in isolated rat hepatocytes have been investigated for oxidative phosphorylation and fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was significantly increased (by 20%) with or without fatty acid addition (octanoate or oleate) in the PUFA-deficient group compared with controls. The effect persisted after oligomycin addition but not after that of potassium cyanide, leading to the conclusion that, in these intact cells, the mitochondria were uncoupled. The PUFA-deficient group exhibited a significant decrease in the cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux. In contrast, glycerol metabolism was significantly enhanced in the PUFA-deficient group. The role of the glycerol 3-phosphate dehydrogenase step in this stimulation was evidenced in hepatocytes perifused with glycerol and octanoate in the presence of increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to an enhancement of glycerol metabolism, as found in PUFA deficiency, although it was more pronounced than in controls. The matrix/cytosol gradients for redox potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats, suggesting a decreased mitochondrial membrane potential in accordance with the uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate dehydrogenase activity in the PUFA-deficient group compared with controls led us to conclude that the activation of glycerol metabolism is the consequence of two mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate dehydrogenase activity.

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Isolated rat hepatocyte metabolism is affected by chronic renal failure

Cited by 23 publications

References 39 publications

Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism

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