bims-hafaim 2022-12-25 papers

bims-hafaim

Biomed News

on Heart failure metabolism

Issue of 2022–12–25
eleven papers selected by
Kyle McCommis, Saint Louis University

FOXO3a-dependent PARKIN negatively regulates cardiac hypertrophy by restoring mitophagy.
Loss of ALDH2 aggravates mitochondrial biogenesis disorder in cardiac myocytes induced by TAC.
DELE1 is protective for mitochondrial cardiomyopathy.
Clinical benefit of sodium-glucose transport protein-2 inhibitors in patients with heart failure: An updated meta-analysis and trial sequential analysis.
Iron Deficiency and Deranged Myocardial Energetics in Heart Failure.
Cardiovascular outcomes in patients treated with sodium-glucose transport protein 2 inhibitors, a network meta-analysis of randomized trials.
SGLT2 Inhibitors in Acute Heart Failure: A Meta-Analysis of Randomized Controlled Trials.
Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.
Knockout of the Complex III subunit Uqcrh causes bioenergetic impairment and cardiac contractile dysfunction.
Exercise Training Upregulates Cardiac mtp Expression in Drosophila melanogaster with HFD to Improve Cardiac Dysfunction and Abnormal Lipid Metabolism.
Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis.

Cell Biosci. 2022 Dec 19. 12(1): 204

FOXO3a-dependent PARKIN negatively regulates cardiac hypertrophy by restoring mitophagy.

Teng Sun, Yu Han, Jia-Lei Li, Xiang-Ying Jiao, Lin Zuo, Jin Wang, Hai-Xiong Wang, Jun-Li Yang, Ji-Min Cao, Jian-Xun Wang.

   BACKGROUND: Sustained cardiac hypertrophy often develops maladaptive myocardial remodeling, and eventually progresses to heart failure and sudden death. Therefore, maladaptive hypertrophy is considered as a critical therapeutic target for many heart diseases. Mitophagy, a crucial mechanism in mitochondria quality control and cellular homeostasis, has been implicated in diverse cardiac disorders such as myocardial infarction, diabetic cardiomyopathy, cardiac hypertrophy and heart failure. However, what role mitophagy plays in heart diseases remains an enigma. PARKIN functions as an E3 ubiquitin protein ligase and mediates mitophagy cascades. It is still unclear whether PARKIN participates in the regulation of cardiac hypertrophy.
RESULTS: PARKIN was downregulated in cardiomyocytes and hearts under hypertrophic stress. Enforced expression of PARKIN inhibited Ang II-induced cardiomyocyte hypertrophy. Compared to wide-type mice with Ang II-induced cardiac hypertrophy, Parkin transgenic mice subjected to Ang II administration showed attenuated cardiac hypertrophy and improved cardiac function. In addition, mitophagy machinery was impaired in response to Ang II, which was rescued by overexpression of PARKIN. PARKIN exerted the anti-hypertrophy effect through restoring mitophagy. In further exploring the underlying mechanisms, we found that PARKIN was transcriptionally activated by FOXO3a. FOXO3a promoted mitophagy and suppressed cardiac hypertrophy by targeting Parkin.
CONCLUSIONS: The present study reveals a novel cardiac hypertrophy regulating model composed of FOXO3a, PARKIN and mitophagy program. Modulation of their levels may provide a new approach for preventing cardiac hypertrophy and heart failure.

Keywords:  Cardiac hypertrophy; FOXO3a; Mitophagy; PARKIN

DOI:  https://doi.org/10.1186/s13578-022-00935-y
Biochem Biophys Res Commun. 2022 Dec 01. pii: S0006-291X(22)01666-7. [Epub ahead of print]639 189-196

Loss of ALDH2 aggravates mitochondrial biogenesis disorder in cardiac myocytes induced by TAC.

Guang Xia, Jianfei Xu, Min Chen, Jifu Jin, Xiaodong Wang, Yong Ye.

  Heart failure is one of the major fatal diseases and mitochondrial biogenesis is an important compensatory mechanism in the process of heart failure. Aldehyde dehydrogenase 2(ALDH2) is an important endogenous cardiac protective factor in mitochondria, but its role in mitochondrial biogenesis of cardiomyocytes remains unknown. In our study, transverse aorta constriction(TAC)-induced heart failure model was established in ALDH2-/- mice and wild-type mice. The cardiac function was examined by echocardiography at 4 weeks after operation. The myocardial tissue was stained by HE. The mitochondria morphology was observed using electron microscope, and the ATP content, Sirt1,PGC-1α and NRF1 expression were measured. Compared with wild-type mice, the cardiac function of ALDH2 -/- mice decreased significantly at 4 weeks after TAC. The proportion of mitochondrial area and mitochondrial crest/mitochondrial ratio decreased in the ALDH2-/- group after TAC. The ATP content decreased in ALDH2 -/- mice at 4 weeks after TAC. In the meantime, the expression of PGC-1α,Sirt 1 and NRF1 decreased in the ALDH2-/- TAC group compared with wild type TAC group.Neonatal rat cardiomyocytes were cultured and stretched. Cardiomyocytes were treated with the activator of ALDH2(Alda-1), Sirt1-SiRNA and PGC-1α-siRNA, respectively. The mitochondrial structure of cardiomyocytes was observed by transmission electron microscopy. The levels of PGC-1α,NRF-1 and Tfam were measured by Western blot.Mitochondrial biogenesis was enhanced in stretch cardiomyocytes treated with Alda-1.When cardiomyocytes were treated with Sirt1-SiRNA or PGC1α-SiRNA, the effect of Alda-1 in promoting mitochondrial biogenesis was attenuated.Therefore, these results suggested that the loss of ALDH2 aggravates mitochondrial biogenesis disorder in cardiac myocytes induced by TAC. Alda-1 could promote mitochondrial biogenesis in stretched cardiomyocytes, and this effect depends on Sirt1/PGC-1α pathway.

Keywords:  ALDH2; Mitochondrial biogenesis; PGC-1α; Sirt1; Transverse aorta constriction

DOI:  https://doi.org/10.1016/j.bbrc.2022.12.001
J Mol Cell Cardiol. 2022 Dec 17. pii: S0022-2828(22)00573-9. [Epub ahead of print]175 44-48

DELE1 is protective for mitochondrial cardiomyopathy.

Helen Huynh, Siting Zhu, Sharon Lee, Yutong Bao, Jing Pang, Anh Nguyen, Yusu Gu, Chao Chen, Kunfu Ouyang, Sylvia M Evans, Xi Fang.

  Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death Enhancer 1 (DELE1) is a mitochondrial protein recently found to be critical for mediating mitochondrial stress-triggered ISR (MSR)-induced eIF2α-ATF4 pathway activation. However, the specific role of DELE1 in heart at baseline or in response to mitochondrial stress remains largely unknown. In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. Conversely, DELE1 is essential for mediating an adaptive response to mitochondrial dysfunction-triggered stress in the heart, playing a protective role in mitochondrial cardiomyopathy.

Keywords:  Dele1; Integrated stress response; Mitochondrial cardiomyopathy; Mitochondrial stress

DOI:  https://doi.org/10.1016/j.yjmcc.2022.12.003
Front Cardiovasc Med. 2022 ;9 1067806

Clinical benefit of sodium-glucose transport protein-2 inhibitors in patients with heart failure: An updated meta-analysis and trial sequential analysis.

Xiehui Chen, Lili Wang, Huijun Li, Weichao Huang, Siquan Huang, Lingyue Zhao, Wenqin Guo.

  To assess whether the current body of accumulated data can give convincing evidence in favor of sodium-glucose transport protein-2 inhibitor (SGLT-2i) in all types of heart failure (HF). We searched for randomized controlled trials contrasting the effectiveness of SGLT-2i to placebo or other hypoglycemic medications on clinicaltrials.gov, PubMed, and the Cochrane Library database. To gauge effect size, hazard ratios (HR) were employed as measurements. The composite outcome of cardiovascular death or hospitalization owing to HF was the primary endpoint. Eleven studies were included. In comparison to the control group, the data demonstrated that SGLT-2i is related with a decreased incidence of composite outcome (HR: 0.77, 95% CIs: 0.73-0.81, I 2 = 0%, P < 0.01), CV death (HR: 0.87, 95% CIs: 0.81-0.94, I 2 = 3%, P < 0.01), all-cause mortality (HR: 0.90, 95% CIs: 0.84-0.96, I 2 = 10%, P < 0.01), and hospitalization due to HF (HHF) (HR: 0.70, 95% CIs: 0.66-0.75, I 2 = 0%, P < 0.01). The trial sequential analysis found strong evidence of a decrease in the incidence of all clinical outcomes with SGLT-2i when compared to the control group. Subgroup analysis demonstrated that the association between SGLT-2i and clinical outcome was independent of population characteristics. We confirm that the present evidence supports the use of SGLT-2i in a wide range of HF patients.
Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022333279].

Keywords:  heart failure; hospitalization due to HF; meta-analysis; sodium-glucose transport protein-2 inhibitors; trial sequential analysis

DOI:  https://doi.org/10.3389/fcvm.2022.1067806
Int J Environ Res Public Health. 2022 Dec 18. pii: 17000. [Epub ahead of print]19(24):

Iron Deficiency and Deranged Myocardial Energetics in Heart Failure.

Michał Tkaczyszyn, Krzysztof Michał Górniak, Weronika Hanna Lis, Piotr Ponikowski, Ewa Anita Jankowska.

  Among different pathomechanisms involved in the development of heart failure, adverse metabolic myocardial remodeling closely related to ineffective energy production, constitutes the fundamental feature of the disease and translates into further progression of both cardiac dysfunction and maladaptations occurring within other organs. Being the component of key enzymatic machineries, iron plays a vital role in energy generation and utilization, hence the interest in whether, by correcting systemic and/or cellular deficiency of this micronutrient, we can influence the energetic efficiency of tissues, including the heart. In this review we summarize current knowledge on disturbed energy metabolism in failing hearts as well as we analyze experimental evidence linking iron deficiency with deranged myocardial energetics.

Keywords:  energy generation; iron deficiency; metabolic derangements; myocardial tissue

DOI:  https://doi.org/10.3390/ijerph192417000
Front Cardiovasc Med. 2022 ;9 1041200

Cardiovascular outcomes in patients treated with sodium-glucose transport protein 2 inhibitors, a network meta-analysis of randomized trials.

Dániel Tornyos, Maximilian Meuer, Réka Lukács, Oumaima El Alaoui El Abdallaoui, Péter Kupó, Réka Faludi, András Komócsi.

   Background: Gliflozins altering the sodium-glucose transport protein 2 (SGLT2) in the nephron, represent alone or in combination a promising treatment option for patients with type II diabetes mellitus. In addition to glucose control, these drugs provide benefits including reduced risk of long-term cardiovascular (CV) and renal complications. Several trials evaluated gliflozins in patients with various degrees of cardiac dysfunction with heterogeneous results.
Objectives: We aimed to perform a comprehensive analysis of the effect of gliflozins on CV outcomes.
Methods: Systematic searches of electronic databases were conducted until September 2022. Multiple treatment network meta-analysis was performed in R. Random-effects model was used to combine risk estimates across trials calculating risk ratio (RR) with 95% confidence intervals as summary statistics. The primary endpoint of interest was the rate of heart failure-related hospitalization (HHF) and the composite of HHF with CV mortality (HHF + CVD). Secondary outcomes included major adverse cardiac events (MACE), CV- and overall mortality, myocardial infarction (MI), and stroke.
Results: Twenty-nine studies randomizing 88,418 patients were identified. Gliflozins reduced the risk of HHF (RR: 0.72 [0.69; 0.76]) and HHF + CVD (RR: 0.78 [0.75; 0.82]). The risk of MACE and its component also improved significantly except for stroke. The network analyses did not explore major differences among the individual substances. The only exception was sotagliflozin which appeared to be more effective regarding HHF + CVD, stroke, and MI compared to ertugliflozin, in HHF + CVD and stroke compared to dapagliflozin, and in stroke endpoint compared to empagliflozin.
Conclusion: Our meta-analysis supports a group effect of gliflozins beneficial in a wide spectrum of patients with a risk of heart failure (HF) development. In addition to the improvement of HF-related outcomes, the risk of major adverse events is also reduced with SGLT2 inhibition.
Systematic review registration: [www.ClinicalTrials.gov], identifier [CRD42022358078].

Keywords:  cardiovascular event; heart failure; major adverse cardiac events (MACE); mortality; network meta-analysis; sodium glucose co-transport-2 (SGLT2) inhibitors

DOI:  https://doi.org/10.3389/fcvm.2022.1041200
Healthcare (Basel). 2022 Nov 23. pii: 2356. [Epub ahead of print]10(12):

SGLT2 Inhibitors in Acute Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Noor Ul Amin, Faiza Sabir, Talal Amin, Zouina Sarfraz, Azza Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda.

  Acute heart failure (AHF) is a major public health concern, affecting 26 million worldwide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering drugs, comprising canagliflozin, dapagliflozin, and empagliflozin that are being explored for AHF. We aim to meta-analyze the effectiveness of SGLT2 inhibitors compared to placebo for primary outcomes including all-cause and cardiovascular mortality, heart failure events, symptomatic improvement, and readmissions. Our secondary outcome is the risk of serious adverse events. This meta-analysis has been designed in accordance with the PRISMA Statement 2020. A systematic search across PubMed, Scopus, and Cochrane Library was conducted through August 13, 2022. The following keywords were utilized: sglt2, sodium-glucose transporter 2 inhibitors, sglt2 inhibitors, decompensated heart failure, de-novo heart failure, and/or acute heart failure. Only randomized controlled trials (RCTs) with adult patients (>18 years), hospitalized with de-novo AHF, acutely decompensated chronic heart failure with reduced, borderline, or preserved ejection, and receiving SGLT2 inhibitors were included. A quantitative analytical methodology was applied where the standardized mean difference (SMD) applying 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) with 95% CI was yielded. All tests were carried out on Review Manager 5.4 (Cochrane). In total, three RCTs were included pooling in a total of 1831 patients where 49.9% received SGLT2 inhibitors. The mean age was 72.9 years in the interventional group compared to 70.6 years in the placebo. Only 33.7% of the sample was female. The follow-up spanned 2-9 months. Heart failure events were reduced by 62% in the interventional group (RR = 0.66, p < 0.0001). readmissions had a reduced risk of 24% with SGLT2 inhibitors (RR = 0.76, p = 0.03). We assessed the efficacy and safety of SGLT2 inhibitors in preventing complications post-AHF. The odds of all-cause mortality, cardiovascular mortality, heart failure events, and re-admissions rates were substantially reduced within the first 1-9 months of hospitalization.

Keywords:  SGLT2 inhibitors; acute heart failure; cardioprotection; cardiovascular mortality; heart failure events

DOI:  https://doi.org/10.3390/healthcare10122356
J Am Heart Assoc. 2022 Dec 24. e027652

Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.

Muhammad Shahzeb Khan, Javed Butler, Stefan D Anker, Gerasimos Filippatos, João Pedro Ferreira, Stuart J Pocock, James L Januzzi, Ileana L Piña, Michael Böhm, Piotr Ponikowski, Subodh Verma, Martina Brueckmann, Ola Vedin, Cordula Zeller, Faiez Zannad, Milton Packer.

  Background Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; P interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. Conclusions Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.

Keywords:  empagliflozin; heart failure; ischemic cause; reduced ejection fraction; sodium‐glucose co‐transporter‐2

DOI:  https://doi.org/10.1161/JAHA.122.027652
Mamm Genome. 2022 Dec 24.

Knockout of the Complex III subunit Uqcrh causes bioenergetic impairment and cardiac contractile dysfunction.

Nadine Spielmann, Christina Schenkl, Tímea Komlódi, Patricia da Silva-Buttkus, Estelle Heyne, Jana Rohde, Oana V Amarie, Birgit Rathkolb, Erich Gnaiger, Torsten Doenst, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Marten Szibor.

Ubiquinol cytochrome c reductase hinge protein (UQCRH) is required for the electron transfer between cytochrome c1 and c of the mitochondrial cytochrome bc1 Complex (CIII). A two-exon deletion in the human UQCRH gene has recently been identified as the cause for a rare familial mitochondrial disorder. Deletion of the corresponding gene in the mouse (Uqcrh-KO) resulted in striking biochemical and clinical similarities including impairment of CIII, failure to thrive, elevated blood glucose levels, and early death. Here, we set out to test how global ablation of the murine Uqcrh affects cardiac morphology and contractility, and bioenergetics. Hearts from Uqcrh-KO mutant mice appeared macroscopically considerably smaller compared to wildtype littermate controls despite similar geometries as confirmed by transthoracic echocardiography (TTE). Relating TTE-assessed heart to body mass revealed the development of subtle cardiac enlargement, but histopathological analysis showed no excess collagen deposition. Nonetheless, Uqcrh-KO hearts developed pronounced contractile dysfunction. To assess mitochondrial functions, we used the high-resolution respirometer NextGen-O2k allowing measurement of mitochondrial respiratory capacity through the electron transfer system (ETS) simultaneously with the redox state of ETS-reactive coenzyme Q (Q), or production of reactive oxygen species (ROS). Compared to wildtype littermate controls, we found decreased mitochondrial respiratory capacity and more reduced Q in Uqcrh-KO, indicative for an impaired ETS. Yet, mitochondrial ROS production was not generally increased. Taken together, our data suggest that Uqcrh-KO leads to cardiac contractile dysfunction at 9 weeks of age, which is associated with impaired bioenergetics but not with mitochondrial ROS production. Global ablation of the Uqcrh gene results in functional impairment of CIII associated with metabolic dysfunction and postnatal developmental arrest immediately after weaning from the mother. Uqcrh-KO mice show dramatically elevated blood glucose levels and decreased ability of isolated cardiac mitochondria to consume oxygen (O2). Impaired development (failure to thrive) after weaning manifests as a deficiency in the gain of body mass and growth of internal organ including the heart. The relative heart mass seemingly increases when organ mass calculated from transthoracic echocardiography (TTE) is normalized to body mass. Notably, the heart shows no signs of collagen deposition, yet does develop a contractile dysfunction reflected by a decrease in ejection fraction and fractional shortening.

DOI: https://doi.org/10.1007/s00335-022-09973-w
Biology (Basel). 2022 Nov 30. pii: 1745. [Epub ahead of print]11(12):

Exercise Training Upregulates Cardiac mtp Expression in Drosophila melanogaster with HFD to Improve Cardiac Dysfunction and Abnormal Lipid Metabolism.

Tianhang Peng, Meng Ding, Hanhui Yan, Qiufang Li, Ping Zhang, Rui Tian, Lan Zheng.

  Current evidence suggests that the heart plays an important role in regulating systemic lipid homeostasis, and high-fat diet (HFD)-induced obesity is a major cause of cardiovascular disease, although little is known about the specific mechanisms involved. Exercise training can reportedly improve abnormal lipid metabolism and cardiac dysfunction induced by high-fat diets; however, the molecular mechanisms are not yet understood. In the present study, to explore the relationship between exercise training and cardiac mtp in HFD flies and potential mechanisms by which exercise training affects HFD flies, Drosophila was selected as a model organism, and the GAL4/UAS system was used to specifically knock down the target gene. Experiments revealed that HFD-fed Drosophila exhibited changes in body weight, increased triglycerides (TG) and dysregulated cardiac contractility, consistent with observations in mammals. Interestingly, inhibition of cardiac mtp expression reduced HFD-induced cardiac damage and mitigated the increase in triglycerides. Further studies showed that in HFD +w1118, HFD + Hand > w1118, and HFD+ Hand > mtpRNAi, cardiac mtp expression downregulation induced by HFD was treated by exercise training and mitochondrial β-oxidation capacity in cardiomyocytes was reversed. Overall, knocking down mtp in the heart prevented an increase in systemic TG levels and protected cardiac contractility from damage caused by HFD, similar to the findings observed after exercise training. Moreover, exercise training upregulated the decrease in cardiac mtp expression induced by HFD. Increased Had1 and Acox3 expression were observed, consistent with changes in cardiac mtp expression.

Keywords:  Drosophila; cardiac dysfunction; exercise training; lipid metabolism; mtp; β-oxidation

DOI:  https://doi.org/10.3390/biology11121745
Life (Basel). 2022 Dec 06. pii: 2034. [Epub ahead of print]12(12):

Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis.

Vera B M Peters, Nishkantha Arulkumaran, Miranda J Melis, Charlotte Gaupp, Thierry Roger, Manu Shankar-Hari, Mervyn Singer.

  Mitochondrial dysfunction and immune cell dysfunction are commonplace in sepsis and are associated with increased mortality risk. The short chain fatty acid, butyrate, is known to have anti-inflammatory effects and promote mitochondrial biogenesis. We therefore explored the immunometabolic effects of butyrate in an animal model of sepsis. Isolated healthy human volunteer peripheral mononuclear cells were stimulated with LPS in the presence of absence of butyrate, and released cytokines measured. Male Wistar rats housed in metabolic cages received either intravenous butyrate infusion or placebo commencing 6 h following faecal peritonitis induction. At 24 h, splenocytes were isolated for high-resolution respirometry, and measurement of mitochondrial membrane potential (MMP), reactive oxygen species (mtROS), and intracellular cytokines (TNF alpha, IL-10) using flow cytometry. Isolated splenocytes from septic and septic butyrate treated rats were stimulated with LPS for 18 h and the effects of butyrate on cytokine release assessed. Ex vivo, butyrate (1.8 mM) reduced LPS-induced TNF alpha (p = 0.019) and IL-10 (p = 0.001) release by human PBMCs. In septic animals butyrate infusion reduced the respiratory exchange ratio (p < 0.001), consistent with increased fat metabolism. This was associated with a reduction in cardiac output (p = 0.001), and increased lactate (p = 0.031) compared to placebo-treated septic animals (p < 0.05). Butyrate treatment was associated with a reduction in splenocyte basal respiration (p = 0.077), proton leak (p = 0.022), and non-mitochondrial respiration (p = 0.055), and an increase in MMP (p = 0.007) and mtROS (p = 0.027) compared to untreated septic animals. Splenocyte intracellular cytokines were unaffected by butyrate, although LPS-induced IL-10 release was impaired (p = 0.039). In summary, butyrate supplementation exacerbates myocardial and immune cell mitochondrial dysfunction in a rat model of faecal peritonitis.

Keywords:  butyrate; fatty acids; immunity; mitochondria; nutrition; sepsis

DOI:  https://doi.org/10.3390/life12122034