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

• Published in: International journal of molecular sciences Vol. 22; no. 23; p. 12695
• Main Authors: Betz, Iris Rosa, Qaiyumi, Sarah Julia, Goeritzer, Madeleine, Thiele, Arne, Brix, Sarah, Beyhoff, Niklas, Grune, Jana, Klopfleisch, Robert, Greulich, Franziska, Uhlenhaut, Nina Henriette, Kintscher, Ulrich, Foryst-Ludwig, Anna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.11.2021; MDPI
• Subjects: Animals; Apoptosis; Cardiomegaly - chemically induced; Cardiomegaly - drug therapy; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomyocytes; Cardiotonic Agents - pharmacology; Catecholamines; Catecholamines - toxicity; Cell cycle; Clinical trials; Dehydrogenases; Ejection fraction; Experiments; Fatty acids; Fatty Acids, Monounsaturated - pharmacology; Gene expression; Gene Expression Regulation - drug effects; Glucose; Hypoxia; Inflammation; Insulin; Kinases; Lipids; Male; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Mortality; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Phosphorylation; Physiology; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR delta - genetics; PPAR delta - metabolism; Proteins; catecholamine; lipokine; PPAR; palmitoleic acid (C16:1n7); cardioprotective effects; cardiac damage
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222312695

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.