Dataset Information

The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart.

ABSTRACT:

Objectives

This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid β-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK).

Materials and methods

Rats with chronic HF, induced by adriamycin (Adr), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-β-D-arabinofuranoside (Ara A, specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside (Aicar, specific AMPK activator) were administered to rats with HF, singly and/or combinedly. Myocardial high-energy phosphate (such as phosphocreatine, ADP, and ATP), free L-Carnitine, malonyl-CoA, and the activity of FAO-related enzymes in left ventricle from different groups were measured by using the corresponding molecular biological techniques.

Results

Gs-Rb1 improved HF significantly, accompanied by a significant increase in phosphocreatine (PCr), ADP, ATP, PCr/ATP ratio, free carnitine, malonyl-CoA, mRNA, activity of carnitine palmitoyltransferase (Cpt), medium-chain Acyl-CoA Dehydrogenase (MCAD) and long-chain acyl-CoA Synthetase (ACSL) and a significant decrease of the ADP/ATP ratio in the left ventricular myocardium. However, all those effects were almost abolished by Ara A and were not further improved by Aicar.

Conclusion

Taken together, it suggests that Gs-Rb1 may modulate cardiac metabolic remodeling by improving myocardial fatty acid β-oxidation in failing heart. In addition, the effects of Gs-Rb1 may be mediated via activating AMPK.

SUBMITTER: Kong HL

PROVIDER: S-EPMC6098964 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart.

Kong Hong-Liang HL Hou Ai-Jie AJ Liu Ning-Ning NN Chen Bo-Han BH Dai Sheng-Nan SN Huang Hua-Ting HT

Iranian journal of basic medical sciences 20180701 7

<h4>Objectives</h4>This study intended to investigate the effects of <i>Ginsenoside-Rbl (Gs-Rbl)</i> on fatty acid β-oxidation (FAO) in rat failing heart and to identify potential mechanisms of <i>Gs-Rbl</i> improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK).<h4>Materials and methods</h4>Rats with chronic HF, induced by adriamycin (<i>Adr</i>), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-β-D-arabinofuranoside (<i>Ara A</i>, specific AMPK inhib ...[more]

PMID: 30140413

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Project description:BackgroundThe failing heart is energy starved with impaired oxidation of long-chain fatty acids (LCFAs) at the level of reduced CPT1 (carnitine palmitoyltransferase 1) activity at the outer mitochondrial membrane. Recent work shows elevated ketone oxidation in failing hearts as an alternate carbon source for oxidative ATP generation. We hypothesized that another short-chain carbon source, short-chain fatty acids (SCFAs) that bypass carnitine palmitoyltransferase 1, could similarly support energy production in failing hearts.MethodsCardiac hypertrophy and dysfunction were induced in rats by transverse-aortic constriction (TAC). Fourteen weeks after TAC or sham operation, isolated hearts were perfused with either the 4 carbon, 13C-labeled ketone (D3-hydroxybutyrate) or the 4 carbon, 13C-labeled SCFA butyrate in the presence of glucose and the LCFA palmitate. Oxidation of ketone and SCFA was compared by in vitro 13C nuclear magnetic resonance spectroscopy, as was the capacity for short-chain carbon sources to compensate for impaired LCFA oxidation in the hypertrophic heart. Adaptive changes in enzyme expression and content for the distinct pathways of ketone and SCFA oxidation were examined in both failing rat and human hearts.ResultsTAC produced pathological hypertrophy and increased the fractional contributions of ketone to acetyl coenzyme-A production in the tricarboxylic acid cycle (0.60±0.02 sham ketone versus 0.70±0.02 TAC ketone; P<0.05). However, butyrate oxidation in failing hearts was 15% greater (0.803±0.020 TAC SCFA) than ketone oxidation. SCFA was also more readily oxidized than ketone in sham hearts by 15% (0.693±0.020 sham SCFA). Despite greater SFCA oxidation, TAC did not change short-chain acyl coenzyme-A dehydrogenase content. However, failing hearts of humans and the rat model both contain significant increases in acyl coenzyme-A synthetase medium-chain 3 enzyme gene expression and protein content. The increased oxidation of SCFA and ketones occurred at the expense of LCFA oxidation, with LCFA contributing less to acetyl coenzyme-A production in failing hearts perfused with SCFA (0.190±0.012 TAC SCFA versus 0.3163±0.0360 TAC ketone).ConclusionsSCFAs are more readily oxidized than ketones in failing hearts, despite both bypassing reduced CPT1 activity and represent an unexplored carbon source for energy production in failing hearts.

Dataset Information

The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart.

Objectives

Materials and methods

Results

Conclusion

Publications

The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart.

Similar Datasets

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