Author:
Liu Yuexia,Li Yizhou,Liang Juntong,Sun Zhuwen,Sun Chao
Abstract
Lysine crotonylation modification is a novel acylation modification that is similar to acetylation modification. Studies have found that protein acetylation plays an important regulatory part in the occurrence and prevention of obesity and is involved in the regulation of glucose metabolism, tricarboxylic acid cycle, white fat browning and fatty acid metabolism. Therefore, we speculate that protein crotonylation may also play a more vital role in regulating the browning of white fat. To verify this conjecture, we identified 7254 crotonyl modification sites and 1629 modified proteins in iWAT of white fat browning model mice by affinity enrichment and liquid chromatography–mass spectrometry (LC-MS/MS). We selected five representative proteins in the metabolic process, namely glycerol-3-phosphate dehydrogenase 1 (GPD1), fatty acid binding protein 4 (FABP4), adenylate kinase 2 (AK2), triosephosphate isomerase 1 (TPI1) and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 (NDUFA8). Through qPCR, Western blotting, immunofluorescence staining, Oil Red O staining and HE staining, we demonstrated that GPD1 and FABP4 inhibited white fat browning, while AK2, TPI1 and NDUFA8 promoted white fat browning. GPD1 and FABP4 proteins were downregulated by crotonylation modification, while AK2, TPI1 and NDUFA8 proteins were upregulated by crotonylation modification. Further detection found that the crotonylation modification of GPD1, FABP4, AK2, TPI1 and NDUFA8 promoted white fat browning, which was consistent with the sequencing results. These results indicate that the protein crotonylation is involved in regulating white fat browning, which is of great significance for controlling obesity and treating obesity-related diseases.
Funder
National Key Research and Development Program of China
Major National Scientific Research Projects
Joint Funds of the National Natural Science Foundation of China
Key Research and Development Projects in Shaanxi Province
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献