scholarly journals Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion

2018 ◽  
Vol 314 (4) ◽  
pp. H787-H795 ◽  
Author(s):  
Qun Chen ◽  
Masood Younus ◽  
Jeremy Thompson ◽  
Ying Hu ◽  
John M. Hollander ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Electron Transport ◽  
Fatty Acid Oxidation ◽  
Electron Transport Chain ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Absolute Quantification ◽  
Intermediary Metabolism ◽  
Acid Oxidation ◽  
Transport Chain

Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.

scholarly journals Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair

2019 ◽  
Vol 29 (2) ◽  
pp. 443-456.e5 ◽  
Author(s):  
Shuang Zhang ◽  
Samuel Weinberg ◽  
Matthew DeBerge ◽  
Anastasiia Gainullina ◽  
Matthew Schipma ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Electron Transport ◽  
Fatty Acid Oxidation ◽  
Electron Transport Chain ◽  
Tissue Repair ◽  
Acid Oxidation ◽  
Transport Chain

Estrogen replacement stimulates fatty acid oxidation and impairs post-ischemic recovery of hearts from ovariectomized female rats

2002 ◽  
Vol 80 (10) ◽  
pp. 1001-1007 ◽  
Author(s):  
Mark Grist ◽  
Richard B Wambolt ◽  
Gregory P Bondy ◽  
Dean R English ◽  
Michael F Allard
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Corn Oil ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Female Rats ◽  
Acid Oxidation ◽  
Estrogen Replacement ◽  
Lipid Utilization ◽  
Intact Rats

Women less than 50 years of age, the majority of whom are likely premenopausal and exposed to estrogen, are at greater risk of a poor short-term recovery after myocardial ischemia than men and older women. Since estrogen enhances non-cardiac lipid utilization and increased lipid utilization is associated with poor post-ischemic heart function, we determined the effect of estrogen replacement on post-ischemic myocardial function and fatty acid oxidation. Female Sprague–Dawley rats, either intact (n = 15) or ovariectomized and treated with 17β-estradiol (0.1 mg·kg–1·day–1, s.c., n = 14) or corn oil vehicle (n = 16) for 5 weeks, were compared. Function and fatty acid oxidation of isolated working hearts perfused with 1.2 mM [9,10-3H]palmitate, 5.5 mM glucose, 0.5 mM lactate, and 100 mU/L insulin were measured before and after global no-flow ischemia. Only 36% of hearts from estrogen-treated rats recovered after ischemia compared with 56% from vehicle-treated rats (p > 0.05, not significant), while 93% of hearts from intact rats recovered (p < 0.05). Relative to pre-ischemic values, post-ischemic function of estrogen-treated hearts (26.3 ± 10.1%) was significantly lower than vehicle-treated hearts (53.4 ± 11.8%, p < 0.05) and hearts from intact rats (81.9 ± 7.0%, p < 0.05). Following ischemia, fatty acid oxidation was greater in estrogen-treated hearts than in the other groups. Thus, estrogen replacement stimulates fatty acid oxidation and impairs post-ischemic recovery of isolated working hearts from ovariectomized female rats.Key words: fatty acid oxidation, estrogen, ischemia, reperfusion.

scholarly journals Retinoic acid exerts sexually dimorphic effects over muscle energy metabolism and function

2021 ◽  
Author(s):  
Yaxin Zhao ◽  
Marta Vuckovic ◽  
Hong Sik Yoo ◽  
Nina Fox ◽  
Adrienne Rodriguez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Electron Transport Chain ◽  
Energy Use ◽  
Acid Oxidation ◽  
Retinol Dehydrogenase ◽  
Transport Chain ◽  
Muscle Energy ◽  
Glut1 Mrna

Among others, the retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and suppresses adiposity. Relative to WT, Rdh10+/- males experienced reduced fatty-acid oxidation, glucose intolerance and insulin resistance. Running endurance decreased 40%. Rdh10+/- females increased reliance on fatty acid oxidation and did not experience glucose intolerance nor insulin resistance. Running endurance improved 2.2-fold. Estrogen increased, revealed by a 40% increase in uterine weight. Because skeletal muscle energy use restricts adiposity and insulin resistance, we assessed the mixed fiber type gastrocnemius muscle (GM) to determine the effects of endogenous RA on muscle metabolism in vivo. RA in Rdh10+/- male GM decreased 38% relative to WT. TAG content increased 1.7-fold. Glut1 mRNA and glucose decreased >30%. Rdh10+/- male GM had impaired electron transport chain activity, and a 60% reduction in fasting ATP. The share of oxidative fibers increased, as did expression of the myogenic transcription factors Myog and Myf5. Centralized nuclei increased 5-fold in fibersindicating muscle malady or repair. In Rdh10+/- female GM, RA decreased only 17%, due to a 1.8-fold increase in the estrogen-induced retinol dehydrogenase, Dhrs9. Rdh10+/- female GM did not amass TAG, increase oxidative fibers, decrease Glut1 mRNA or glucose, nor increase centralized nuclei. Expression of Myog and Myf5 decreased. Electron transport chain activity increased, elevating fasting ATP >3-fold. Thus, small decreases in skeletal muscle RA affect whole body energy use, insulin resistance and adiposity, in part through estrogen-related sexual dimorphic effects on mitochondria function.

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