Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes

Sparagna, Genevieve C.; Jones, Chris; Hickson-Bick, Diane L.

doi:10.1152/ajpheart.00247.2004

Cited by 14 publications

(12 citation statements)

References 61 publications

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“…This observation is consistent with previous studies, which suggest that a high concentration of palmitic acid decreases mitochondrial membrane potential, and the ability of the mitochondria to produce ROS [34,35]. Provision of a low concentration of metformin (1 or 2 mmol/l) restored ROS to control levels, probably due to the effect of metformin in promoting fatty acid oxidation and electron flow through the mitochondrial electron transport chain [35]. In contrast, in the presence of palmitic acid, cardiomyocytes treated with 5 mmol/l metformin exhibited the lowest ROS level.…”

Section: Discussionsupporting

confidence: 93%

Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3

et al. 2006

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Aims/hypothesis Metformin has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK). We hypothesised that metformin could prevent both caspase-3 activation and apoptosis when induced by palmitic acid. Materials and methods Cardiomyocytes were incubated with 1 mmol/l palmitic acid, in the absence or presence of metformin (1-5 mmol/l). Following 1 to 16 h, cell damage was evaluated by measuring lactate dehydrogenase released into the incubation medium, and Hoechst staining. To investigate the mechanism of metformin's effect on cardiomyocytes, substrate utilisation and phosphorylation of AMPK and acetyl-CoA carboxylase were measured. Intracellular mediators of apoptosis were also evaluated. Results Incubation of myocytes with palmitic acid for 16 h increased apoptosis, an effect that was partly blunted by 1 and 2 mmol/l metformin. This beneficial effect of metformin was associated with increased AMPK phosphorylation, palmitic acid oxidation and suppression of high-fat-induced increases in (1) long chain base biosynthesis protein 1 levels, (2) ceramide levels, and (3) caspase-3 activity. Unexpectedly, 5 mmol/l metformin dramatically increased apoptosis in myocytes incubated with high fat. This effect was associated with a robust increase in glycolysis, lactate accumulation, and a significant drop of pH in the myocyte incubation medium. Conclusions/interpretation Our study demonstrates that metformin reduces high-fat-induced cardiac cell death, probably through inhibition of ceramide synthesis. However, at high concentrations, metformin causes proton and lactate accumulation, leading to cell damage that is independent of caspase-3.

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Section: Discussionsupporting

confidence: 93%

Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3

et al. 2006

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“…Saturated fatty acids such as palmitic acid stimulated AMPK activity in the presence of ethanol in cardiomyocytes. 36 We also observed that PGC-1␣ promoter activity in vitro is modified by various fatty acids only in the presence of ethanol (unpublished data). These direct effects could be, in part, due to the differences in the metabolism of PUFA and HSF in the presence or absence of ethanol.…”

Section: Discussionmentioning

confidence: 62%

Role of Adiponectin in the Protective Action of Dietary Saturated Fat Against Alcoholic Fatty Liver in Mice * #

et al. 2005

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The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP-activated protein kinase, PPAR-␣, and PPAR-␥ coactivator ␣, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3-L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy-nutritional modulation of adiponectin-in treating human alcoholic fatty liver disease. (HEPATOLOGY 2005;42:568 -577.)

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“…Second, it is possible that a counteractive effect may exist between ethanol and a high-fat diet. For example, ethanol attenuates fatty acid-induced apoptosis in neonatal rat cardiomyocytes [54] . Diets rich in saturated fatty acids protect against alcoholic liver injury [55][56][57][58][59][60] .…”

Section: Wwwchinapharcom Feng L Et Almentioning

confidence: 99%

Long-term ethanol exposure inhibits glucose transporter 4 expression via an AMPK-dependent pathway in adipocytes

Song

Guan

et al. 2010

Acta Pharmacol Sin

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Aim:The roles of AMP-activated protein kinase (AMPK) and myocyte enhancer factor 2 isoforms (MEF2A, D) as mediators of the effects of ethanol on glucose transporter 4 (GLUT4) expression are unclear. We studied the effects of ethanol in adipocytes in vivo and in vitro. Methods: Thirty-six male Wistar rats were divided into three groups and given ethanol in a single daily dose of 0, 0.5, or 5 g/kg for 22 weeks. The expression of AMPK, MEF2 isoforms A and D, and GLUT4 was measured and compared in the three groups. The existence of the AMPK/MEF2/GLUT4 pathway in adipocytes and the effects of ethanol on this pathway were studied in (a) epididymal adipose tissue from six male Wistar rats subcutaneously injected with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR, an AMPK activator) or with 0.9% NaCl (control); and (b) isolated rat and human adipocytes treated with or without ethanol, AICAR, and compound C (a selective AMPK inhibitor). Expression of AMPK, MEF2, and GLUT4 was measured by RT-PCR and Western blotting. Results: (1) Long-term ethanol exposure decreased activated AMPK, MEF2A, MEF2D, and GLUT4 expression in rat adipose tissue. (2) In rat and human adipocytes, AICAR-induced AMPK activation, with subsequent elevation of MEF2 and GLUT4 expression, was inhibited by compound C. (3) In vitro ethanol-treatment suppressed the AMPK/MEF2/GLUT4 pathway. Conclusion: The AMPK/MEF2/GLUT4 pathway exists in both rat and human adipocytes, and activated AMPK may positively regulate MEF2 and GLUT4 expression. Ethanol inhibition of this pathway leads to decreased GLUT4 expression, thus reducing insulin sensitivity and glucose tolerance.

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Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes

Abstract: . Attenuation of fatty acid-induced apoptosis by lowdose alcohol in neonatal rat cardiomyocytes.

Cited by 14 publications

References 61 publications

Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3

Metformin influences cardiomyocyte cell death by pathways that are dependent and independent of caspase-3

Role of Adiponectin in the Protective Action of Dietary Saturated Fat Against Alcoholic Fatty Liver in Mice * #

Long-term ethanol exposure inhibits glucose transporter 4 expression via an AMPK-dependent pathway in adipocytes

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