Metabolomic profiling analysis reveals chamber-dependent metabolite patterns in the mouse heart

Abstract

Energy of the cardiac muscle largely depends on fatty acid oxidation. It is known that the atrium and ventricle have chamber-specific functions, structures, gene expressions, and pathologies. The left ventricle works as a high-pressure chamber to pump blood toward the body, and its muscle wall is thicker than those of the other chambers, suggesting that energy utilization in each of the chambers should be different. However, a chamber-specific pattern of metabolism remains incompletely understood. Recently, innovative techniques have enabled the comprehensive analysis of metabolites. Therefore, we aimed to clarify differences in metabolic patterns among the chambers. Male C57BL6 mice at 6 wk old were subject to a comprehensive measurement of metabolites in the atria and ventricles by capillary electrophoresis and mass spectrometry. We found that overall metabolic profiles, including nucleotides and amino acids, were similar between the right and left ventricles. On the other hand, the atria exhibited a distinct metabolic pattern from those of the ventricles. Importantly, the high-energy phosphate pool (the total concentration of ATP, ADP, and AMP) was higher in both ventricles. In addition, the levels of lactate, acetyl CoA, and tricarboxylic acid cycle contents were higher in the ventricles. Accordingly, the activities and/or expression levels of key enzymes were higher in the ventricles to produce more energy. The present study provides a basis for understanding the chamber-specific metabolism underlining pathophysiology in the heart.

Heterozygous deletion of sarcolipin maintains normal cardiac function

“…After echocardiography, heart tissues were immediately isolated under isoflurane anesthesia, as previously described (33). Hearts were separated into three parts (both atria, the LV, and the right ventricle) and immediately frozen with liquid nitrogen after each tissue's weight was measured.…”

“…We performed quantitative RT-PCR as previously described (33). Briefly, total RNA was extracted from atria using TRIzol reagent (Invitrogen, Carlsbad, CA) or Sepasol RNA I Super G (Nacalai Tesque) as recommended by the manufac- …”

“…Previous research has clarified that the atrium has distinct characteristics from the ventricle in terms of function and structure as well as gene expression and metabolic profile (4,33,36). There are fewer studies on the atrium compared with those on the ventricle.…”

Capillary electrophoresis mass spectrometry based metabolomics

“…Importantly, CE also gives complementary information to HILIC [13], as well as, significantly better peak shape in many cases. It is therefore not surprising that CE-MS has already been considered for multiple metabolomics studies covering several applications, from aging [19], amino acid analysis [20,21] [46][47][48][49][50][51][52][53], CVD [54][55][56][57][58], diabetes [59][60][61][62][63][64][65], lifestyle [61][62][63][64][65][66][67][68][69][70][71], kidney disease [72,73], liver disease [74][75][76][77][78][79][80][81][82], the microbiome [83][84]…”

Mechanisms increasing n-3 highly unsaturated fatty acids in the heart

“…Therefore, it should be considered that atrial and ventricular myocardium exhibit different metabolic profiles, which appear to be attributed, at least in part, to different load conditions, particularly increased wall stress Rupp et al 2011). In the atrium, the expression of carnitin-palmitoyltransferase (CPT) -1b and -2 was reported to a lesser extent than in the ventricle (Shimura et al 2013). CPT is responsible for the uptake of 24:6n-3 from endoplasmic reticulum to the peroxisome, the location of beta-oxidation and the last step of 22:6n-3 synthesis.…”