SIRT3-mediated Mitochondrial Autophagy in Refeeding Syndrome-related Myocardial Injury in Sepsis Rats

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2022 Mar 14

PMID 35280405

Authors

Jiucui Li

Kongmiao Lu

Xiao Zhang

Tianying Wang

Qinghai Li

Xinjuan Yu

Wei Han

Lixin Sun

Affiliations

Soon will be listed here.

Abstract

Background: Myocardial injury induced by refeeding syndrome (RFS) is one of the important causes of deterioration in critically ill patients. Sirtuin-3 (SIRT3) has been shown to regulate mitochondrial autophagy in myocardial ischemia/reperfusion injury; however, the role of mitochondrial autophagy on RFS-related myocardial injury in patients in critical condition has not been reported on.

Methods: Thirty Sprague-Dawley (SD) rats were divided into 3 groups (n=10 each group): the control group; the standard calorie refeeding (SCR) group; and the low calorie refeeding (LCR) group. The rats were weighed every third or four days from day 1 to day 14. On day 14, all rats were anesthetized and received an echocardiography test. Blood and bronchoalveolar lavage fluid (BALF) were collected and tested for arterial oxygen pressure (PaO), phosphorus (P), and calcium (Ca), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin 1 (cTnI), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6. The histopathological change of hearts and lungs were evaluated, and lung injury score was calculated. Mitochondrial autophagy related proteins (including Beclin1, LC3, mitofusin-2, Mfn2, PINK1, Parkin, and SIRT3) were analyzed using a Western blot. To evaluate the effect of SIRT3, 20 rats were divided into 2 groups (n=10 each group): The adeno-associated virus 9 (AAV9-Nc) group; and the AAV9-SIRT3 overexpression (AAV9-SIRT3) group. The protocols for rats were the same as the SCR group since day 22 after injection of AAV9. The protein expressions of PINK1, Parkin, and SIRT3 were compared between the AAV9-Nc group and AAV9-SIRT3 group.

Results: SCR caused significant decline in cardiac contractility and increased inflammatory cell infiltration in myocardial tissue. Meanwhile, Beclin1, LC3, PINK1, Parkin, and SIRT3 levels decreased, while Mfn2 showed no significant change. Furthermore, significant positive correlations were also found between SIRT3 and P, PINK1, and Parkin, and significant negative correlations were found between SIRT3 and CK-MB, LDH, and cTnI. Overexpression of SIRT3 activated the PINK1/Parkin mediated mitochondrial autophagy.

Conclusions: SIRT3 has an essential role in RFS-related myocardial injury during LPS induced chronic sepsis in rats, probably via regulating mitochondrial autophagy.

Citing Articles

Epigenetic factors and inflammaging: FOXO3A as a potential biomarker of sarcopenia and upregulation of DNMT3A and SIRT3 in older adults.

Bogucka D, Wajda A, Stypinska B, Radkowski M, Targowski T, Modzelewska E Front Immunol. 2025; 16:1467308.

PMID: 40034697 PMC: 11872893. DOI: 10.3389/fimmu.2025.1467308.

Erratum: SIRT3-mediated mitochondrial autophagy in refeeding syndrome-related myocardial injury in sepsis rats.

Ann Transl Med. 2025; 12(6):124.

PMID: 39817243 PMC: 11729808. DOI: 10.21037/atm-2024-53.

Crosstalk among mitophagy, pyroptosis, ferroptosis, and necroptosis in central nervous system injuries.

Zhang L, Hu Z, Li Z, Lin Y Neural Regen Res. 2023; 19(8):1660-1670.

PMID: 38103229 PMC: 10960298. DOI: 10.4103/1673-5374.389361.

The Current State of Research on Sirtuin-Mediated Autophagy in Cardiovascular Diseases.

Wang Y, Li Y, Ding H, Li D, Shen W, Zhang X J Cardiovasc Dev Dis. 2023; 10(9).

PMID: 37754811 PMC: 10531599. DOI: 10.3390/jcdd10090382.

References

Parodi-Rullan R, Chapa-Dubocq X, Guzman-Hernandez R, Jang S, A Torres-Ramos C, Ayala-Pena S . The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells. Cells. 2019; 8(10). PMC: 6829619. DOI: 10.3390/cells8101247. View

Parodi-Rullan R, Chapa-Dubocq X, Javadov S . Acetylation of Mitochondrial Proteins in the Heart: The Role of SIRT3. Front Physiol. 2018; 9:1094. PMC: 6090200. DOI: 10.3389/fphys.2018.01094. View

Boateng A, Sriram K, Meguid M, Crook M . Refeeding syndrome: treatment considerations based on collective analysis of literature case reports. Nutrition. 2010; 26(2):156-67. DOI: 10.1016/j.nut.2009.11.017. View

Olthof L, Koekkoek W, van Setten C, Kars J, van Blokland D, van Zanten A . Impact of caloric intake in critically ill patients with, and without, refeeding syndrome: A retrospective study. Clin Nutr. 2017; 37(5):1609-1617. DOI: 10.1016/j.clnu.2017.08.001. View

Nguyen T, Padman B, Lazarou M . Deciphering the Molecular Signals of PINK1/Parkin Mitophagy. Trends Cell Biol. 2016; 26(10):733-744. DOI: 10.1016/j.tcb.2016.05.008. View

Wan S, Yang J, Mamtawla G, Zhang L, Gao X, Wang X . Differential Metabolomic Analysis of Liver Tissues from Rat Models of Parenteral Nutrition-Associated Liver Disease. Biomed Res Int. 2020; 2020:9156359. PMC: 7115143. DOI: 10.1155/2020/9156359. View

Zheng Y, Shi B, Ma M, Wu X, Lin X . The novel relationship between Sirt3 and autophagy in myocardial ischemia-reperfusion. J Cell Physiol. 2018; 234(5):5488-5495. DOI: 10.1002/jcp.27329. View

Kane A, Sinclair D . Sirtuins and NAD in the Development and Treatment of Metabolic and Cardiovascular Diseases. Circ Res. 2018; 123(7):868-885. PMC: 6206880. DOI: 10.1161/CIRCRESAHA.118.312498. View

Khan L, Ahmed J, Khan S, MacFie J . Refeeding syndrome: a literature review. Gastroenterol Res Pract. 2010; 2011. PMC: 2945646. DOI: 10.1155/2011/410971. View

10.

Hoshino A, Wang W, Wada S, McDermott-Roe C, Evans C, Gosis B . The ADP/ATP translocase drives mitophagy independent of nucleotide exchange. Nature. 2019; 575(7782):375-379. PMC: 6858570. DOI: 10.1038/s41586-019-1667-4. View

11.

Rocha A, Franco A, Krezel A, Rumsey J, Alberti J, Knight W . MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A. Science. 2018; 360(6386):336-341. PMC: 6109362. DOI: 10.1126/science.aao1785. View

12.

Xu Y, Zhang S, Rong J, Lin Y, Du L, Wang Y . Sirt3 is a novel target to treat sepsis induced myocardial dysfunction by acetylated modulation of critical enzymes within cardiac tricarboxylic acid cycle. Pharmacol Res. 2020; 159:104887. DOI: 10.1016/j.phrs.2020.104887. View

13.

Singer P, Reintam Blaser A, Berger M, Alhazzani W, Calder P, Casaer M . ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2018; 38(1):48-79. DOI: 10.1016/j.clnu.2018.08.037. View

14.

Zhao D, Sun Y, Tan Y, Zhang Z, Hou Z, Gao C . Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice. Oxid Med Cell Longev. 2018; 2018:4079041. PMC: 5925211. DOI: 10.1155/2018/4079041. View

15.

Morel J, Hargreaves I, Brealey D, Neergheen V, Backman J, Lindig S . Simvastatin pre-treatment improves survival and mitochondrial function in a 3-day fluid-resuscitated rat model of sepsis. Clin Sci (Lond). 2017; 131(8):747-758. DOI: 10.1042/CS20160802. View

16.

Li R, Xin T, Li D, Wang C, Zhu H, Zhou H . Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy. Redox Biol. 2018; 18:229-243. PMC: 6079484. DOI: 10.1016/j.redox.2018.07.011. View

17.

Peng M, Liu Y, Zhang X, Xu Y, Zhao Y, Yang H . CTRP5-Overexpression Attenuated Ischemia-Reperfusion Associated Heart Injuries and Improved Infarction Induced Heart Failure. Front Pharmacol. 2021; 11:603322. PMC: 7783420. DOI: 10.3389/fphar.2020.603322. View

18.

Yang P, Li Z, Tye K, Chen Y, Lu T, He Z . Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy. BMC Pregnancy Childbirth. 2020; 20(1):216. PMC: 7161261. DOI: 10.1186/s12884-020-02905-z. View

19.

Kirk R, Kesner R, Wang L, Wu Q, Towner R, Hoffman J . Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits. Geroscience. 2019; 41(4):467-481. PMC: 6815307. DOI: 10.1007/s11357-019-00089-9. View

20.

Doig G, Simpson F, Heighes P, Bellomo R, Chesher D, Caterson I . Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med. 2015; 3(12):943-52. DOI: 10.1016/S2213-2600(15)00418-X. View