Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice. Issue 13 (9th July 2019)

• Record Type: Journal Article
• Authors: Li, Chen; Niu, Yan; Zheng, Hong; Shan, Congjia; Chen, Qinbo; Yang, Zhongzhou; Zhao, Liangcai; Yang, Changwei; Gao, Hongchang
• Is Part Of: Biochemical journal. Volume 476:Issue 13(2019)
• Page Start: 1943
• Page End: 1954
• Publication Date: 2019-07-09
• Subjects: heart failure -- metabolic remodeling -- metabolomics -- mitochondrial respiration -- PDK1; Biochemistry -- Periodicals; 572
• DOI: 10.1042/BCJ20190105
• Languages: English
• ISSNs: 0264-6021

Abstract

Abstract : Metabolic remodeling plays an essential role in the pathophysiology of heart failure (HF). Many studies have shown that the disruption of phosphoinositide-dependent protein kinase-1 (PDK1) caused severe and lethal HF; however, the metabolic pattern of PDK1 deletion remains ambiguous. 1 H nuclear magnetic resonance-based metabolomics was applied to explore the altered metabolic pattern in Pdk1- deficient mice. Principle component analysis showed significant separation as early as 4 weeks of age, and dysfunction of metabolism precedes a morphological change in Pdk1- deficient mice. A time trajectory plot indicated that disturbed metabolic patterns were related to the pathological process of the HF in Pdk1- deficient mice, rather than the age of mice. Metabolic profiles demonstrated significantly increased levels of acetate, glutamate, glutamine, and O -phosphocholine in Pdk1 deletion mice. Levels of lactate, alanine, glycine, taurine, choline, fumarate, IMP, AMP, and ATP were significantly decreased compared with controls. Furthermore, PDK1 knockdown decreased the oxygen consumption rate in H9C2 cells as determined using a Seahorse XF96 Analyzer. These findings imply that the disruption of metabolism and impaired mitochondrial activity might be involved in the pathogenesis of HF with PDK1 deletion.