Short-Chain Fatty Acids Outpace Ketone Oxidation in the Failing Heart
| Autor: | Yang Wang, Matthew Fasano, Craig H. Selzman, Santosh K. Maurya, E. Douglas Lewandowski, Stavros G. Drakos, Andrew N. Carley |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Ketone Failing heart 030204 cardiovascular system & hematology Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Carnitine palmitoyltransferase 1 Physiology (medical) Internal medicine medicine Animals Humans 030304 developmental biology Heart Failure chemistry.chemical_classification 0303 health sciences business.industry Short-chain fatty acid Metabolism Ketones Fatty Acids Volatile medicine.disease Rats Disease Models Animal Endocrinology chemistry Heart failure lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine business Oxidation-Reduction |
| Zdroj: | Circulation |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.120.052671 |
| Popis: | Background: The 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. Methods: Cardiac 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, 13 C-labeled ketone (D3-hydroxybutyrate) or the 4 carbon, 13 C-labeled SCFA butyrate in the presence of glucose and the LCFA palmitate. Oxidation of ketone and SCFA was compared by in vitro 13 C 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. Results: TAC 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 Conclusions: SCFAs 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. |
| Databáze: | OpenAIRE |
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