Glutamate–oxaloacetate transaminase activity promotes palmitate lipotoxicity in rat hepatocytes by enhancing anaplerosis and citric acid cycle flux

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Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.

To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures ...

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BACKGROUND/AIMS Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO) in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate sin...

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Ameliorative Role of Palmitoleic Acid on Palmitate Induced Lipotoxicity in the Rat Cardiomyocytes

Background: Co-supplementation of unsaturated fatty acids (FAs) with saturated FAs may decrease the adverse effects of saturated FA-induced lipotoxicity. The objective of the present study was to evaluate the effect of palmitoleic acid (unsaturated fatty acid) on palmitic acid (saturated fatty acid) induced lipotoxicity criteria in the primary culture of adult rat cardiomyocytes. Methods: Ce...

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Control of citric acid cycle activity in rat heart mitochondria.

Rat heart mitochondria were incubated in state 3 (with ADP) or state 4 (without ADP) in the presence of [3J4C]pyruvate, [3J4C]pyruvate plus unlabeled malate, or unlabeled pyruvate plus uniformly labeled [14C]malate. The net accumulation or loss of each intermediate in the citric acid cycle was determined by specific enzyme assays. In addition, the incorporation of radioactivity into cycle inter...

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The key role of anaplerosis and cataplerosis for citric acid cycle function.

The oxidation of acetyl-CoA to CO2 by the TCA 1 cycle is the central process in energy metabolism. However, the TCA cycle also functions in biosynthetic pathways in which intermediates leave the cycle to be converted primarily to glucose, fatty acids, or non-essential amino acids. If TCA cycle anions are removed from the cycle they must be replaced to permit its continued function. This process...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2019

ISSN: 0021-9258

DOI: 10.1074/jbc.ra118.004869