Acute hypoxic preconditioning prevents palmitic acid‐induced cardiomyocyte apoptosis via switching metabolic GLUT4‐glucose pathway back to CD36‐fatty acid dependent

Abstract

Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short-term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short-term hypoxia in the heart has a protective effect, but long-term hypoxia increases myocardial cell injury. Palmitic acid (PA)-treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4). We exposed the cells to short- and long-term hypoxia and investigated the protective effects of hypoxic preconditioning on PA-induced lipotoxicity in H9c2 cardiomyoblasts and neonatal rat cardiomyocytes. Preconditioning with short-term hypoxia enhanced both CD36 and GLUT4 metabolism pathway protein levels. Expression levels of phospho-PI3K, phospho-Akt, phospho-AMPK, SIRT1, PGC1α, PPARα, CD36, and CPT1β induced by PA was reversed by short-term hypoxia in a time-dependent manner. PA-induced increased GLUT4 membrane protein level was reduced in the cells exposed to short-term hypoxia and si-PKCζ. Short-term hypoxia, resveratrol and si-PKCζ rescue H9c2 cells from apoptosis induced by PA and switch the metabolic pathway from GLUT4 dependent to CD36 dependent. We demonstrate short-term hypoxic preconditioning as a more efficient way as resveratrol in maintaining the energy metabolism of hearts during hyperlipidemia and can be used as a therapeutic strategy.

Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

“…Hypertension is a global multiple disease, the prevalence of the elderly is increasing year by year, and hypertrophy of the cardiac muscle caused by constant stress overload is a bad outcome of it. Hypertension can cause changes in myocardial energy metabolism, and these changes rapidly reduce the oxidation rate of fatty acids and its enzymatic expression and activity [1][2][3].…”

miR-21 promotes non-small cell lung cancer cells growth by regulating fatty acid metabolism

“…Previous study demonstrated that LNMICC accelerated metastasis by reprogramming fatty acid metabolism in cervical cancer [22]. CD36 is a receptor for lipids and fatty acids and plays an important role in metabolic syndrome and related cardiac activities, which involved in lipid metabolism, long-chain fatty acid adsorption, apoptotic residue clearance, and macrophage phagocytosis [23–25]. Studies have found that CD36-regulated fatty acid metabolism is closely related to tumorigenesis and development [26, 27].…”

Nifuroxazide ameliorates lipid and glucose metabolism in palmitate-induced HepG2 cells

“…Fatty acids not only cause fat accumulation and inammatory reaction in liver cells in vitro but also induce insulin resistance 33 and impair glucose transport and glucose metabolism. 34 In our present research, we discussed that intracellular glycogen synthesis was increased by Nifu in HepG2 cells aer PA treatment. In addition, PA treatment was found to result in a signicant increase in the protein and mRNA expression of PEPCK and G6Pase, which are key gluconeogenesis enzymes.…”