Sodium octanoate mediates GPR84-dependent and independent protection against sepsis-induced myocardial dysfunction

Yao Lin; Wenbin Zhang; Xiangkang Jiang; Chenghao Wu; Jingyuan Yang; Jiawei Tao; Ziwei Chen; Jiantao He; Ruojie Zhu; Huiming Zhong; Jinbo Zhang; Jiefeng Xu; Zhaocai Zhang; Mao Zhang

Biomedicine & Pharmacotherapy (Nov 2024)

Sodium octanoate mediates GPR84-dependent and independent protection against sepsis-induced myocardial dysfunction

Yao Lin,
Wenbin Zhang,
Xiangkang Jiang,
Chenghao Wu,
Jingyuan Yang,
Jiawei Tao,
Ziwei Chen,
Jiantao He,
Ruojie Zhu,
Huiming Zhong,
Jinbo Zhang,
Jiefeng Xu,
Zhaocai Zhang,
Mao Zhang

Affiliations

Yao Lin: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Wenbin Zhang: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Xiangkang Jiang: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Chenghao Wu: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Jingyuan Yang: Department of Dermatology, Air Force Medical Center, PLA, Beijing, 100142, China
Jiawei Tao: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Ziwei Chen: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Jiantao He: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Ruojie Zhu: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Huiming Zhong: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China
Jinbo Zhang: Department of Emergency Medicine, The First People's Hospital of Wenling, Wenling 317500, China
Jiefeng Xu: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China; Corresponding authors at: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Zhaocai Zhang: Department of Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Corresponding author.
Mao Zhang: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burns of Zhejiang Province, Hangzhou 310009, China; Clinical Research Center for Emergency and Critical Care Medicine of Zhejiang Province, Hangzhou 310009, China; Corresponding authors at: Department of Emergency Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.

Journal volume & issue: Vol. 180
p. 117455

Abstract

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Introduction: This study aims to evaluate the therapeutic effects of sodium octanoate (SO), a medium-chain fatty acid salt, on SIMD in a murine model and to explore its underlying mechanisms. Methods: Male mice were subjected to sepsis models through two methods: intraperitoneal injection of lipopolysaccharide (LPS) and cecal ligation and punction (CLP). Mice received interval doses of SO every 2 hours or 4 hours for a total of six times or three times after LPS treatment. The relationship between SO and G protein-coupled receptor 84 (GPR84) was evaluated through GEO data analysis and molecular docking studies. DBA/2 mice were used to study the role of the GPR84 protein in the SO-mediated protection. Energy metabolomics was utilized to comprehensively assess the impact of SO on the levels of cardiac energy metabolic products in septic mice. histone modification identification techniques were used to further identify the specific sites of histone modification in the hearts of SO-treated septic mice. Results: SO treatment significantly improved myocardial contractile function, restored the oxidative stress imbalance and enhanced the myocardium's resistance to oxidative injury. SO significantly promotes the expression of GPR84. The loss of GPR84 function markedly attenuates the protective effects of SO. SO enhanced myocardial energy metabolism by promoting the synthesis of acetyl-CoA and upregulating genes involved in fatty acid β-oxidation which were abolished by medium-chain acyl-CoA dehydrogenase (MCAD) knockdown. SO induced histone acetylation, particularly at H3K123 and H3K80. Conclusion: Our study demonstrates that SO exerts protective effects against SIMD through both GPR84-mediated anti-inflammatory and antioxidant actions and GPR84-independent enhancement of myocardial energy metabolism, possibly mediated by MCAD.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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