Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid β-oxidation to alleviate diabetic cardiomyopathy

Autor: Meng-Yuan Jiang, Wan-Rong Man, Xue-Bin Zhang, Xiao-Hua Zhang, Yu Duan, Jie Lin, Yan Zhang, Yang Cao, De-Xi Wu, Xiao-Fei Shu, Lei Xin, Hao Wang, Xiao Zhang, Cong-Ye Li, Xiao-Ming Gu, Xuan Zhang, Dong-Dong Sun
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Military Medical Research, Vol 10, Iss 1, Pp 1-17 (2023)
Druh dokumentu: article
ISSN: 2054-9369
DOI: 10.1186/s40779-023-00493-5
Popis: Abstract Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism. Methods A high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator. Results The expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P
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