title: Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC zeta-GLUT4-glucose pathway in cardiomyoblasts.
abstract: Metabolic regulation is inextricably linked with cardiac function. Fatty acid metabolism is a significant mechanism for creating energy for the heart. However, cardiomyocytes are able to switch the fatty acids or glucose, depending on different situations, such as ischemia or anoxia. Lipotoxicity in obesity causes impairments in energy metabolism and apoptosis in cardiomyocytes. We utilized the treatment of H9c2 cardiomyoblast cells palmitic acid (PA) as a model for hyperlipidemia to investigate the signaling mechanisms involved in these processes. Our results show PA induces time- and dose-dependent lipotoxicity in H9c2 cells. Moreover, PA enhances cluster of differentiation 36 (CD36) and reduces glucose transporter type 4 (GLUT4) pathway protein levels following a short period of treatment, but cells switch from CD36 back to the GLUT4 pathway after during long-term exposure to PA. As sirtuin 1 (SIRT1) and protein kinase Cζ (PKCζ) play important roles in CD36 and GLUT4 translocation, we used the SIRT1 activator resveratrol and si-PKCζ to identify the switches in metabolism. Although PA reduced CD36 and increased GLUT4 metabolic pathway proteins, when we pretreated cells with resveratrol to activate SIRT1 or transfected si-PKCζ, both were able to significantly increase CD36 metabolic pathway proteins and reduce GLUT4 pathway proteins. High-fat diets affect energy metabolism pathways in both normal and aging rats and involve switching the energy source from the CD36 pathway to GLUT4. In conclusion, PA and high-fat diets cause lipotoxicity in vivo and in vitro and adversely switch the energy source from the CD36 pathway to the GLUT4 pathway.
authors.affiliation: Ph.D. Program for Aging, China Medical University, Taichung, Taiwan; Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Yeh-Peng
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Ph.D. Program for Aging, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan.
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan.
authors.forename: Cecilia-Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: Department of pathology, Changhua Christian Hospital, Changhua, Taiwan; Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.affiliation: Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Chinese Medicine Department, China Medical University Beigang Hospital, Taichung, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore -641 046, India.
authors.forename: V Vijaya
authors.initials: VV
authors.lastname: Padma
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. Electronic address: cyhuang@mail.cmu.edu.tw.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D004734:Energy Metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism*; D000099221:Protein Kinase C zeta
chemical_list: D018955:CD36 Antigens; D051275:Glucose Transporter Type 4; D019308:Palmitic Acid; D011493:Protein Kinase C; D056564:Sirtuin 1; D000099221:Protein Kinase C zeta
keywords: Cardiomyoblast apoptosis; Energy metabolism; PKCζ-GLUT4-glucose pathway; Palmitic acid; SIRT1-CD36-fatty acid pathway