scholarly journals Short Chain Fatty Acids Outpace Ketone Oxidation in the Failing Heart

Circulation ◽  
2021 ◽  
Author(s):  
Andrew N. Carley ◽  
Santosh K. Maurya ◽  
Matthew Fasano ◽  
Yang Wang ◽  
Craig H. Selzman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Carbon Source ◽  
Energy Production ◽  
Tricarboxylic Acid Cycle ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Sham Operation ◽  
Acetyl Coa ◽  
Failing Heart ◽  
Chain Fatty Acids

Background: The failing heart is energy-starved with impaired oxidation of long chain fatty acids (LCFA) at the level of reduced carnitine palmitoyltransferase 1 (CPT1) 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 (SCFA) that bypass CPT1, could similarly support energy production in failing hearts. Methods: Cardiac hypertrophy and dysfunction was induced in rats by transverse-aortic constriction (TAC). 14 weeks after TAC or sham-operation, isolated hearts were perfused with either the four carbon, 13 C-labeled ketone (D3-hydroxybutyrate) or the four 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 NMR 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 CoA production in the tricarboxylic acid cycle (0.60±0.02 sham ketone vs 0.70±0.02 TAC ketone, p<0.05). However, butyrate oxidation in failing hearts was 15% greater (0.803±0.02 TAC SCFA) than ketone oxidation. SCFA was also more readily oxidized than ketone in sham hearts by 15% (0.693±0.02 sham SCFA). Despite greater SFCA oxidation, TAC did not change short chain acyl CoA dehydrogenase content. However, failing hearts of humans and the rat model both contain significant increases in acyl CoA 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 CoA production in failing hearts perfused with SCFA (0.19±0.012 TAC SCFA vs. 0.3163±0.036 TAC ketone). Conclusions: SCFA are more readily oxidized than ketones in failing hearts, despite both bypassing reduced CPT1 activity, and represents an unexplored carbon source for energy production in failing hearts.

Interaction of short-chain fatty acids carbon source on denitrification

2016 ◽  
Vol 38 (15) ◽  
pp. 1915-1925 ◽  
Author(s):  
Yue Chen ◽  
Liang Guo ◽  
Jiawen Zhang ◽  
Yangguo Zhao ◽  
Mengchun Gao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Carbon Source ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Integrating the extracellular, intracellular, and intercellular metabolic processes of Escherichia coli through glucose saturation, inhibition of the acetyl-CoA carboxylase subunit accA with asRNA, and through quantifying cell to cell quorum-sensing

2019 ◽  
Author(s):  
Tatiana Hillman ◽  
Cory Tobin
Keyword(s):  
Escherichia Coli ◽  
Fatty Acids ◽  
Quorum Sensing ◽  
Bacterial Cell ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Acetyl Coa Carboxylase ◽  
Metabolic Processes ◽  
Acetyl Coa ◽  
Chain Fatty Acids

The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.

scholarly journals Integrating the extracellular, intracellular, and intercellular metabolic processes of Escherichia coli through glucose saturation, inhibition of the acetyl-CoA carboxylase subunit accA with asRNA, and through quantifying cell to cell quorum-sensing

2019 ◽  
Author(s):  
Tatiana Hillman ◽  
Cory Tobin
Keyword(s):  
Escherichia Coli ◽  
Fatty Acids ◽  
Quorum Sensing ◽  
Bacterial Cell ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Acetyl Coa Carboxylase ◽  
Metabolic Processes ◽  
Acetyl Coa ◽  
Chain Fatty Acids

The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.

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