Effects of fatty acids on uncoupling protein‐2 expression in the rat heart

Lee, Karin A.J.M. van der; Willemsen, P. H. M.; Vusse, Ger J.; Bilsen, Marc van

doi:10.1096/fasebj.14.3.495

Cited by 59 publications

(54 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, protein content in H9c2 cells was increased dose-dependently with WY-14,643. This data is supported by a report describing increased expression of uncoupling protein-2 (UCP-2) by WY-14,643 exposure in H9c2 cells (Van Der Lee et al, 2000). Uncoupling protein-2 is known to uncouple oxidative phosphorylation by moving protons across the mitochondrial matrix and mediates the fatty acid-induced uncoupling effects observed in the heart (Fleury et al, 1997).…”

Section: Discussionsupporting

confidence: 53%

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

et al. 2001

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that can be activated by xenobiotics and natural fatty acids. To assess the potential physiological activity of PPAR ligands on cardiac muscular cells, the effects of PPAR agonist, WY-14,643, on both rat hearts and a rat cardiomyocyte cell line (H9c2 cells) were investigated. Male F344 rats were fed a diet containing WY-14,643 at a concentration of 100 ppm for 26 weeks. Cardiac muscular hypertrophy was revealed by morphometric analysis in which the diameter of the muscular fibers in WY-14,643-treated rats was larger than those of control rats. Using H9c2 cells in vitro, the protein content per cell was increased in a dosedependent manner with the treatment of WY-14,643. The transcription of myosin light chain-2 (MLC-2), a parameter of myocardial hypertrophy, was increased in H9c2 cells transfected with the rat MLC-2/luciferase fusion gene by WY-14,643 as well as other peroxisome proliferators, clofibrate and di(2-ethylhexyl) phthalate. In addition, accumulation of myosin light chain protein was confirmed in H9c2 cells treated with WY-14,643 at 10 g/ml for 7 days or more by immunohistochemistry. These results suggest that PPAR ligands have a potential to regulate MLC-2, which is a contractile protein in cardiomyocytes and may play a part of role in the pathogenesis of cardiac hypertrophy.

show abstract

Section: Discussionsupporting

confidence: 53%

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Data obtained by Van Der Lee et al in adult rat heart failed to demonstrate an increase of UCP2 gene expression in conditions of high NEFA plasma levels due to fasting and streptozotocin-induced diabetes. 50 On the other hand, these experimental conditions appear to be quite different from our model, mainly because of the different levels of insulin. Moreover the fact that in isolated neonatal cardiomyocytes fatty acids were able to stimulate UCP2 gene expression to a significant extent, along with a panel of genes encoding proteins known to be involved in cardiac fatty acid transport and metabolism, strongly suggests a relationship between UCP2 and fatty acid handling.…”

Section: Nefa and Gene Expression In Rat Heartcontrasting

confidence: 58%

“…Moreover the fact that in isolated neonatal cardiomyocytes fatty acids were able to stimulate UCP2 gene expression to a significant extent, along with a panel of genes encoding proteins known to be involved in cardiac fatty acid transport and metabolism, strongly suggests a relationship between UCP2 and fatty acid handling. 50,16 An involvement of the uncoupling proteins has been hypothesized in the uncoupling effect of heart muscle mitochondria by high NEFA concentrations, 17,18 that could decrease the ATP formation and the heart work efficiency in the diabetic rat. 51 More recently, however, the putative uncoupling effect of these proteins has been questioned.…”

Section: Nefa and Gene Expression In Rat Heartmentioning

confidence: 99%

Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle

et al. 2002

View full text Add to dashboard Cite

OBJECTIVE: It has been reported that an increased availability of free fatty acids (NEFA) not only interferes with glucose utilization in insulin-dependent tissues, but may also result in an uncoupling effect of heart metabolism. We aimed therefore to investigate the effect of an increased availability of NEFA on gene expression of proteins involved in transmembrane fatty acid (FAT=CD36) and glucose (GLUT4) transport and of the uncoupling proteins UCP2 and 3 at the heart and skeletal muscle level. STUDY DESIGN: Euglycemic hyperinsulinemic clamp was performed after 24 h Intralipid 1 plus heparin or saline infusion in lean Zucker rats. Skeletal and heart muscle glucose utilization was calculated by 2-deoxy-[1-3 H]-D-glucose technique. Quantification of FAT=CD36, GLUT4, UCP2 and UCP3 mRNAs was obtained by Northern blot analysis or RT-PCR. RESULTS: In Intralipid 1 plus heparin infused animals a significant decrease in insulin-mediated glucose uptake was observed both in the heart (22.62 AE 2.04 vs 10.37 AE 2.33 ng=mg=min; P < 0.01) and in soleus muscle (13.46 AE 1.53 vs 6.84 AE 2.58 ng=mg=min; P < 0.05). FAT=CD36 mRNA was significantly increased in skeletal muscle tissue ( þ 117.4 AE 16.3%, P < 0.05), while no differences were found at the heart level in respect to saline infused rats. A clear decrease of GLUT4 mRNA was observed in both tissues. The 24 h infusion of fat emulsion resulted in a clear enhancement of UCP2 and UCP3 mRNA levels in the heart (99.5 AE 15.3 and 80 AE 4%) and in the skeletal muscle (291.5 AE 24.7 and 146.9 AE 12.7%). CONCLUSIONS: As a result of the increased availability of NEFA, FAT=CD36 gene expression increases in skeletal muscle, but not at the heart level. The augmented lipid fuel supply is responsible for the depression of insulin-mediated glucose transport and for the increase of UCP2 and 3 gene expression in both skeletal and heart muscle.

show abstract

“…The H9c2 cell line derived from embryonic rat hearts maintains some features of cardiac myocytes and has been used extensively in in vitro studies (45)(46)(47). In the present study, we selected the H9c2 cell line instead of neonatal cardiomyocytes as used in our previous studies (25)(26)(27)(28) for the following reasons: 1) the glucose transporting system in H9c2 cells has been investigated and does not differ from that in rat or mouse hearts (45,46); 2) as compared with neonatal cardiomyocyte culture, culturing of H9c2 cells is much easier and the phenotypes of the cultures are repeatable, but primary neonatal cardiomyocyte cultures are affected by individual differences among the litters of mice; however, additional study to understand the effect of hyperglycemia directly on myocardial cells in vivo is necessary.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia-Induced Apoptosis in Mouse Myocardium

et al. 2002

View full text Add to dashboard Cite

Diabetic cardiomyopathy is related directly to hyperglycemia. Cell death such as apoptosis plays a critical role in cardiac pathogenesis. Whether hyperglycemia induces myocardial apoptosis, leading to diabetic cardiomyopathy, remains unclear. We tested the hypothesis that apoptotic cell death occurs in the diabetic myocardium through mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetic mice produced by streptozotocin and H9c2 cardiac myoblast cells exposed to high levels of glucose were used. In the hearts of diabetic mice, apoptotic cell death occurred as detected by terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) assay. Correspondingly, caspase-3 activation as determined by enzymatic assay and mitochondrial cytochrome c release detected by Western blotting analysis were observed. Supplementation of insulin inhibited diabetesinduced myocardial apoptosis as well as suppressed hyperglycemia. To explore whether apoptosis in diabetic hearts is related directly to hyperglycemia, we exposed cardiac myoblast H9c2 cells to high levels of glucose (22 and 33 mmol/l) in cultures. Apoptotic cell death was detected by TUNEL assay and DAPI nuclear staining. Caspase-3 activation with a concomitant mitochondrial cytochrome c release was also observed. Apoptosis or activation of caspase-3 was not observed in the cultures exposed to the same concentrations of mannitol. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-cmk, suppressed apoptosis induced by high levels of glucose. In addition, reactive oxygen species (ROS) generation was detected in the cells exposed to high levels of glucose. These results suggest that hyperglycemia directly induces apoptotic cell death in the myocardium in vivo. Hyperglycemiainduced myocardial apoptosis is mediated, at least in part, by activation of the cytochrome c-activated caspase-3 pathway, which may be triggered by ROS derived from high levels of glucose.

show abstract

Effects of fatty acids on uncoupling protein‐2 expression in the rat heart

Cited by 59 publications

References 51 publications

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

Peroxisome proliferator-activated receptor .ALPHA. (PPAR.ALPHA.) agonist, WY-14,643, increased transcription of myosin light chain-2 in cardiomyocytes.

Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle

Hyperglycemia-Induced Apoptosis in Mouse Myocardium

Contact Info

Product

Resources

About