Cardioprotective Effects of Palmitoleic Acid (C16:1n7) in a Mouse Model of Catecholamine-Induced Cardiac Damage Are Mediated by PPAR Activation.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Cardiomegaly/*drug therapy ; Cardiotonic Agents/*pharmacology ; Catecholamines/*toxicity ; Fatty Acids, Monounsaturated/*pharmacology ; Gene Expression Regulation/*drug effects ; PPAR alpha/*metabolism ; PPAR delta/*metabolism; Animals ; Cardiomegaly/chemically induced ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; PPAR alpha/genetics ; PPAR delta/genetics

Palmitoleic acid (C16:1n7) has been identified as a regulator of physiological cardiac hypertrophy. In the present study, we aimed to investigate the molecular pathways involved in C16:1n7 responses in primary murine cardiomyocytes (PCM) and a mouse model of isoproterenol (ISO)-induced cardiac damage. PCMs were stimulated with C16:1n7 or a vehicle. Afterwards, RNA sequencing was performed using an Illumina HiSeq sequencer. Confirmatory analysis was performed in PCMs and HL-1 cardiomyocytes. For an in vivo study, 129 sv mice were orally treated with a vehicle or C16:1n7 for 22 days. After 5 days of pre-treatment, the mice were injected with ISO (25 mg/kg/d s. c.) for 4 consecutive days. Cardiac phenotyping was performed using echocardiography. In total, 129 genes were differentially expressed in PCMs stimulated with C16:1n7, including Angiopoietin-like factor 4 ( Angptl4 ) and Pyruvate Dehydrogenase Kinase 4 ( Pdk4 ). Both Angptl4 and Pdk4 are proxisome proliferator-activated receptor α/δ (PPARα/δ) target genes. Our in vivo results indicated cardioprotective and anti-fibrotic effects of C16:1n7 application in mice. This was associated with the C16:1n7-dependent regulation of the cardiac PPAR-specific signaling pathways. In conclusion, our experiments demonstrated that C16:1n7 might have protective effects on cardiac fibrosis and inflammation. Our study may help to develop future lipid-based therapies for catecholamine-induced cardiac damage.

J Cardiol. 2016 Jan;67(1):22-7. (PMID: 26359712)
Proteins. 2022 Jan;90(1):258-269. (PMID: 34414600)
Lancet. 2007 Sep 29;370(9593):1129-36. (PMID: 17905165)
Mol Cell. 1999 Mar;3(3):397-403. (PMID: 10198642)
Atherosclerosis. 2015 Aug;241(2):641-8. (PMID: 26117401)
Circ Res. 2014 May 23;114(11):1815-26. (PMID: 24855204)
Adv Nutr. 2017 Jan 17;8(1):173S-181S. (PMID: 28096141)
BMJ. 2015 Aug 11;351:h3978. (PMID: 26268692)
Nat Rev Cardiol. 2017 Jan;14(1):30-38. (PMID: 27708278)
Eur Heart J. 2021 Feb 11;42(6):681-683. (PMID: 33447845)
Biochem Biophys Res Commun. 2015 Mar 27;459(1):54-9. (PMID: 25712520)
J Am Heart Assoc. 2021 Jul 20;10(14):e019473. (PMID: 34227403)
PLoS Genet. 2018 Jan 10;14(1):e1007171. (PMID: 29320510)
PLoS One. 2011;6(7):e21209. (PMID: 21750705)
Cell. 2008 Sep 19;134(6):933-44. (PMID: 18805087)
Eur J Echocardiogr. 2009 May;10(3):350-6. (PMID: 19246500)
Life Sci. 2015 Mar 1;124:41-9. (PMID: 25636810)
J Lipid Res. 1997 Jul;38(7):1384-94. (PMID: 9254064)
J Mol Cell Cardiol. 2011 Jun;50(6):940-50. (PMID: 21385587)
Am J Physiol Heart Circ Physiol. 2011 Jul;301(1):H115-22. (PMID: 21478409)
Am J Clin Nutr. 2010 Dec;92(6):1350-8. (PMID: 20943795)
J Biol Chem. 2015 Sep 25;290(39):23603-15. (PMID: 26260790)
Science. 2011 Oct 28;334(6055):528-31. (PMID: 22034436)
Mol Med Rep. 2021 Oct;24(4):. (PMID: 34328199)
Eur Heart J. 2016 Apr 1;37(13):1072-8. (PMID: 26396230)
J Am Soc Echocardiogr. 2017 Dec;30(12):1239-1250.e2. (PMID: 29066223)
J Endocrinol. 2007 Jan;192(1):149-58. (PMID: 17210752)
Eur Heart J. 2016 Feb 1;37(5):449-54. (PMID: 26497163)
Nutr Metab Cardiovasc Dis. 2016 Mar;26(3):261-7. (PMID: 26817937)
Cardiovasc Res. 2021 Jun 01;:. (PMID: 34061169)
Biochim Biophys Acta. 2007 Aug;1771(8):926-35. (PMID: 17433773)
EBioMedicine. 2015 Sep 06;2(10):1513-22. (PMID: 26629547)
Nat Rev Mol Cell Biol. 2013 Jan;14(1):38-48. (PMID: 23258295)
Int J Mol Sci. 2018 Jul 10;19(7):. (PMID: 29996502)
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4318-23. (PMID: 9113987)
Front Cardiovasc Med. 2018 Jun 06;5:68. (PMID: 29928647)
Circ Heart Fail. 2012 Nov;5(6):703-9. (PMID: 23065037)
Nat Rev Immunol. 2010 May;10(5):365-76. (PMID: 20414208)
Nat Protoc. 2016 Oct;11(10):1889-907. (PMID: 27606777)
Dev Cell. 2006 Dec;11(6):791-801. (PMID: 17141155)
Crit Rev Food Sci Nutr. 2018 May 3;58(7):1122-1130. (PMID: 28001085)
Cardiovasc Res. 2021 May 25;117(6):1450-1488. (PMID: 33135058)
Hypertension. 2019 Aug;74(2):295-304. (PMID: 31291149)
Prog Lipid Res. 2011 Jan;50(1):14-27. (PMID: 21087632)
Am J Physiol Endocrinol Metab. 2013 Nov 1;305(9):E1093-102. (PMID: 24022867)
Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H1-9. (PMID: 12623780)
Circulation. 2014 Nov 11;130(20):1790-9. (PMID: 25266948)
J Vis Exp. 2018 Jul 26;(137):. (PMID: 30102264)
Am J Cardiol. 2012 Aug 15;110(4):539-44. (PMID: 22579341)
J Biol Chem. 1997 Feb 7;272(6):3324-9. (PMID: 9013572)
Diabetes. 2002 Apr;51(4):901-9. (PMID: 11916905)
Circ Res. 2016 May 27;118(11):1736-51. (PMID: 27230639)
Int J Mol Sci. 2021 Jul 28;22(15):. (PMID: 34360868)
Diabetes Care. 2010 Feb;33(2):405-7. (PMID: 19889804)
Arch Biochem Biophys. 2011 Jul;511(1-2):1-7. (PMID: 21530483)

Keywords: PPAR; cardiac damage; cardioprotective effects; catecholamine; lipokine; palmitoleic acid (C16:1n7)

0 (Cardiotonic Agents)
0 (Catecholamines)
0 (Fatty Acids, Monounsaturated)
0 (PPAR alpha)
0 (PPAR delta)
209B6YPZ4I (palmitoleic acid)

Date Created: 20211210 Date Completed: 20211217 Latest Revision: 20211217

20231215

PMC8657733

10.3390/ijms222312695

34884498