Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases

Chenyu Li; Chuanbin Liu; Junfeng Zhang; Yanyu Lu; Bingtong Jiang; Huabao Xiong; Chunxia Li

doi:10.3389/fimmu.2023.1296687

Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases

Front Immunol. 2023 Dec 18:14:1296687. doi: 10.3389/fimmu.2023.1296687. eCollection 2023.

Authors

Chenyu Li¹, Chuanbin Liu², Junfeng Zhang¹, Yanyu Lu¹, Bingtong Jiang¹, Huabao Xiong¹, Chunxia Li¹

Affiliations

¹ Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China.
² Department of Pediatric Dentistry, Jining Stomatological Hospital, Jining, Shandong, China.

Abstract

Macrophages are highly heterogeneous and plastic, and have two main polarized phenotypes that are determined by their microenvironment, namely pro- and anti-inflammatory macrophages. Activation of pro-inflammatory macrophages is closely associated with metabolic reprogramming, especially that of aerobic glycolysis. Mitochondrial pyruvate dehydrogenase kinase (PDK) negatively regulates pyruvate dehydrogenase complex activity through reversible phosphorylation and further links glycolysis to the tricarboxylic acid cycle and ATP production. PDK is commonly associated with the metabolism and polarization of macrophages in metabolic and inflammatory diseases. This review examines the relationship between PDK and macrophage metabolism and discusses the mechanisms by which PDK regulates macrophage polarization, migration, and inflammatory cytokine secretion in metabolic and inflammatory diseases. Elucidating the relationships between the metabolism and polarization of macrophages under physiological and pathological conditions, as well as the regulatory pathways involved, may provide valuable insights into the etiology and treatment of macrophage-mediated inflammatory diseases.

Keywords: inflammation; macrophage; metabolic reprogramming; polarization; pyruvate dehydrogenase kinase.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Citric Acid Cycle*
Macrophage Activation*
Macrophages
Phosphorylation
Pyruvate Dehydrogenase Acetyl-Transferring Kinase

Substances

Pyruvate Dehydrogenase Acetyl-Transferring Kinase

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University (grant no. JYHL2021MS06, JYHL2022ZD02).