Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice.
BACKGROUND
Results from different trails have provided evidence of protective effects of cis-9,trans-11-conjugated linoleic acid (CLA) on cardiovascular diseases. But the inhibition of prolyl hydroxylase 1 (PHD1) associated with induction of hypoxia inducible factors (HIFs) by CLA in these protective effects has never been reported before. The objective of this study was to evaluate if the two predominant cis-9,trans-11 (c9, t11), trans-10,cis-12 (t10, c12) CLA isomers and mixture of these two isomers can inhibit PHD1 with induction of HIFs in myocardium in mice and subsequent effects on myocardium metabolism.


RESULTS
CLA mixture and c9, t11 CLA inhibited PHD1 protein expression and increased the levels of protein and mRNA in HIF-2α in myocardium in mice. Meanwhile, CLA mixture and c9, t11 CLA also elevated the expression of HIF related transcriptional factors like PDK4 and PPARα. The reprogramming of basal metabolism in myocardium in mice was shown on increasing of GLUT4 gene expression by c9, t11 CLA supplemented group. UCP2 was increased by CLA mixture and c9, t11 CLA for attenuating production of ROS.


CONCLUSIONS
CLA mixture and c9, t11 CLA could inhibit PHD1 and induce HIF-2α in myocardium in mice, which is associated with upregulation of PDK4 by activation of PPARα. This process also implies a reprogramming of basal metabolism and oxidative damage protection in myocardium in mice. All the effects shown in hearts of mice are due to c9, t11 CLA but not t10, c12 CLA.
National Key Laboratory of Animal Nutrition, College Animal Science and Technology, China Agricultural University, Beijing 100193, People's Republic of China.
Jize
J
Zhang
Defa
D
Li
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011897:Random Allocation; D013237:Stereoisomerism; D000071246:Uncoupling Protein 2; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D002316:Cardiotonic Agents; D002334:Carnitine O-Palmitoyltransferase; D051275:Glucose Transporter Type 4; D051793:Hypoxia-Inducible Factor 1; D007473:Ion Channels; D044243:Linoleic Acids, Conjugated; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D011393:Procollagen-Proline Dioxygenase; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D000071246:Uncoupling Protein 2; D000099162:Endothelial PAS Domain-Containing Protein 1; C000631439:Pdk4 protein, mouse; C495693:Slc2a4 protein, mouse; C000604390:Ucp2 protein, mouse; C522721:PHD1 protein, mouse; C558401:CPT1B protein, mouse