IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

Guo, Xiaoyu; Hong, Ting; Zhang, Shen; Wei, Yazhong; Jin, Haizhen; Miao, Qing; Wang, Kai; Zhou, Miao; Wang, Chong; He, Bin

doi:10.3389/fcell.2021.736603

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…The disorder of lipid metabolism increases reactive oxygen species (ROS) production and fission of mitochondrial, leading to mitochondrial dysfunction and cell apoptosis ( 7 – 9 ). Recent studies have revealed the disorder of lipid metabolism in several kinds of sepsis-induced organ injury ( 10 , 11 ), which has also been observed in septic myocardial tissue in our previous work ( 12 ), however, via unclear mechanisms.…”

Section: Introductionmentioning

confidence: 57%

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Lipocalin-2 participates in sepsis-induced myocardial injury by mediating lipid accumulation and mitochondrial dysfunction

Liu

Guo

Jin

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSepsis-induced cardiomyopathy (SIC) is one major cause of death for sepsis but lacks timely diagnosis and specific treatment due to unclear mechanisms. Lipocalin-2 (LCN-2) is a key regulator of lipid metabolism which has been recently proved closely related to sepsis, however, the relationship between LCN-2 and septic myocardial injury remains unknown. We aim to explore the role of LCN-2 in the pathological progress of SIC based on clinical and laboratory evidence.MethodsConsecutive patients admitted to the intensive care unit (ICU) from August 2021 to April 2022 fulfilling the criteria of severe sepsis were included. The level of LCN-2 in plasma was assayed and analyzed with clinical characteristics. Biostatistical analysis was performed for further identification and pathway enrichment. Mouse model for SIC was thereafter established, in which plasma and tissue LCN-2 levels were tested. RNA sequencing was used for verification and to reveal the possible mechanism. Mitochondrial function and intracellular lipid levels were assayed to further assess the biological effects of targeting LCN-2 in cardiomyocytes with small interference RNAs (siRNAs).ResultsThe level of LCN-2 in plasma was markedly higher in patients with severe sepsis and was associated with higher cardiac biomarkers and lower LVEF. In the in vivo experiment, circulating LCN-2 from plasma was found to increase in SIC mice. A higher level of LCN-2 transcription in myocardial tissue was also found in SIC and showed a clear time relationship. RNA sequencing analysis showed the level of LCN-2 was associated with several gene-sets relevant to mitochondrial function and lipid metabolism-associated pathways. The suppression of LCN-2 protected mitochondrial morphology and limited the production of ROS, as well as restored the mitochondrial membrane potential damaged by LPS. Neutral lipid staining showed prominent lipid accumulation in LPS group, which was alleviated by the treatment of siLCN2.ConclusionThe level of LCN-2 is significantly increased in SIC at both circulating and tissue levels, which is correlated with the severity of myocardial injury indicators, and may work as an early and great predictor of SIC. LCN-2 probably participates in the process of septic myocardial injury through mediating lipid accumulation and affecting mitochondrial function.

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Section: Introductionmentioning

confidence: 57%

“…The cellular model of SIC was established by lipopolysaccharide (LPS, Sigma-Aldrich, United States) incubation based on reported protocol ( 12 , 24 ). Briefly, H9C2 cells were cultured in DMEM containing 10 μg/ml LPS for 12 h. Morphology of cardiomyocytes was observed.…”

Section: Methodsmentioning

confidence: 99%

Lipocalin-2 participates in sepsis-induced myocardial injury by mediating lipid accumulation and mitochondrial dysfunction

Liu

Guo

Jin

et al. 2022

Front. Cardiovasc. Med.

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“… 43 , 44 Inhibition of FAO instigates metabolic reprogramming, disturbing the equilibrium in substrate utilization and leading to the accumulation of excess TGs in the myocardium. 10 , 45 This also inhibits mitochondrial function, 12 fosters apoptosis, 46 induces cellular stress, and contributes to the occurrence of arrhythmias, 47 ultimately exacerbating myocardial injury 48 as a phenomenon known as cardiac lipotoxicity. Supporting our data, UA reduces TG accumulation and restores this mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A protects severe acute pancreatitis‐associated acute cardiac injury by regulating mitochondrial fatty acid oxidative metabolism in cardiomyocytes

Yang,

Hu,

Kang

et al. 2023

MedComm

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Severe acute pancreatitis (SAP) often develops into acute cardiac injury (ACI), contributing to the high mortality of SAP. Urolithin A (UA; 3,8‐dihydroxy‐6H‐dibenzopyran‐6‐one), a natural polyphenolic compound, has been extensively studied and shown to possess significant anti‐inflammatory effects. Nevertheless, the specific effects of UA in SAP‐associated acute cardiac injury (SACI) have not been definitively elucidated. Here, we investigated the therapeutic role and mechanisms of UA in SACI using transcriptomics and untargeted metabolomics analyses in a mouse model of SACI and in vitro studies. SACI resulted in severely damaged pancreatic and cardiac tissues with myocardial mitochondrial dysfunction and mitochondrial metabolism disorders. UA significantly reduced the levels of lipase, amylase and inflammatory factors, attenuated pathological damage to pancreatic and cardiac tissues, and reduced myocardial cell apoptosis and oxidative stress in SACI. Moreover, UA increased mitochondrial membrane potential and adenosine triphosphate production and restored mitochondrial metabolism, but the efficacy of UA was weakened by the inhibition of CPT1. Therefore, UA can attenuate cardiac mitochondrial dysfunction and reduce myocardial apoptosis by restoring the balance of mitochondrial fatty acid oxidation metabolism. CPT1 may be a potential target. This study has substantial implications for advancing our understanding of the pathogenesis and drug development of SACI.

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“…Studies have reported that IL13 is associated with mitochondrial dysfunction in patients with sialadenitis [ 14 ] and protects the mitochondria of cardiomyocytes in patients with septicemia [ 13 ]. Increased IL13 expression has been reported in the dysfunctional mitochondria of mice with house dust mite-induced asthma [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL13 frequently accompanies mitochondria-related conditions, including in infectious disease [ 13 ], inflammatory diseases [ 14 ], and metabolic diseases [ 15 ] and even in cancers [ 16 ]. IL13 has also been reported to be associated with mitochondrial dysfunction in an animal-induced asthma model [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

IL13 Promoter (−1055) Polymorphism Associated with Leukocyte Mitochondria DNA Copy Number in Chronic Obstructive Pulmonary Disease

Liu

Chang

et al. 2022

Cells

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IL13 polymorphism is associated with chronic obstructive pulmonary disease (COPD). Patients with COPD have smaller numbers of mitochondria deoxyribonucleic acid copies (mtDNA-CN) than people without COPD do. However, whether IL13 polymorphism affects the mutation and recombination of mitochondria remains unclear. Data for patients with COPD and non-COPD were collected from Kaohsiung Chang Gung Memorial Hospital to enable a comparison of their leukocyte mtDNA-CN and the association of this information with IL-13 promoter (−1055) polymorphism. This study included 99 patients with COPD and 117 individuals without COPD. The non-COPD individuals included 77 healthy individuals that never smoked and 40 healthy smokers. The patients with COPD exhibited significantly lower mtDNA-CN than non-COPD did (250.34 vs. 440.03; p < 0.001); mtDNA-CN was particularly pronounced in individuals with the IL13 CC and CT genotypes compared with individuals with the TT genotype. When only individuals without COPD were considered and when all participants were considered, the differences in the mtDNA-CNs in individuals with the CC and CT genotypes were more significant than those in individuals with the TT genotype (448.4 and 533.6 vs. 282.8; p < 0.05 in non-COPD group); (368.8 and 362.6 vs. 249.6, p < 0.05 in all participants). The increase mtDNA-CN in the CC and CT genotypes was also more than that in the TT genotype in COPD patients, but showed no significance (260.1 and 230.5 vs. 149.9; p = 0.343). The finding shows that COPD is a mitochondria regulatory disorder and IL-13 promoter (−1055) polymorphism is associated with leukocyte mtDNA-CN. Developing COPD control methods based on mitochondrial regulation will be possible.

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IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria

Cited by 5 publications

References 24 publications

Lipocalin-2 participates in sepsis-induced myocardial injury by mediating lipid accumulation and mitochondrial dysfunction

Lipocalin-2 participates in sepsis-induced myocardial injury by mediating lipid accumulation and mitochondrial dysfunction

Urolithin A protects severe acute pancreatitis‐associated acute cardiac injury by regulating mitochondrial fatty acid oxidative metabolism in cardiomyocytes

IL13 Promoter (−1055) Polymorphism Associated with Leukocyte Mitochondria DNA Copy Number in Chronic Obstructive Pulmonary Disease

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