Metabolic remodeling of cardiomyocyte identified in phosphoinositide-dependent kinase 1-deficient mice.

Metabolic remodeling of cardiomyocyte identified in phosphoinositide-dependent kinase 1-deficient mice. Biochem J. 2019 Jun 17;: Authors: Li C, Niu Y, Zheng H, Shan C, Chen Q, Yang Z, Zhao L, Yang C, Gao H Abstract Metabolic remodeling plays an essential role in the pathophysiology of heart failure. Many studies have shown that disruption of phosphoinositide-dependent protein kinase-1 (PDK1) caused severe and lethal heart failure, however, the metabolic pattern of PDK1 deletion remain ambiguous. 1H NMR-based metabolomics was applied to explore the altered metabolic pattern in Pdk1 deficient mice. Principle components analysis (PCA) showed significant separation as early as 4 weeks-age, dysfunction of metabolism precedes morphological change in Pdk1 deficient mice. Time trajectory plot indicated that disturbed metabolic patterns were related to the pathological process of the heart failure 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. Further, PDK1 knockdown decreased oxygen consumption rate in H9C2 cells as determined using Seahorse XF96 Analyzer. These findings imply that disruption of metabolism and impaired mitochondrial activity might be involved in th...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research