Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC-GLUT4-glucose pathway in cardiomyoblasts

Yeh Peng Chen, Chia Wen Tsai, Chia Yao Shen, Cecilia Hsuan Day, Yu Lan Yeh, Ray Jade Chen, Tsung Jung Ho, V. Vijaya Padma, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)137-149
Number of pages13
JournalJournal of Nutritional Biochemistry
Volume31
DOIs
Publication statusPublished - May 1 2016

Keywords

  • Cardiomyoblast apoptosis
  • Energy metabolism
  • Palmitic acid
  • PKCζ-GLUT4-glucose pathway
  • SIRT1-CD36-fatty acid pathway

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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