Multi-omics integrative analysis to access role of coiled-coil domain-containing 80 in lipid metabolism

Abstract

Coiled-coil domain-containing 80 (Ccdc80) is closely linked to energy homeostasis. However, the molecular mechanism remains unclear. This study aims to uncover the potential mechanism of Ccdc80 in modulating lipid metabolism by accessing the metabolic and transcriptional consequences of removing Ccdc80. We established a Ccdc80 knockout model (Ccdc80−/−) in C57BL/6 mouse. Serum and liver samples from Ccdc80+/+ (n = 8) and Ccdc80−/− (n = 8) male mice were obtained at the age of week 10. The serum metabolites and lipids were analyzed by gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, respectively. RNA expression microarray was performed in the livers of the same mice. Results showed that a total of 58 metabolites and 30 lipids were altered between the Ccdc80+/+ and Ccdc80−/− mice. A total of 873 hepatic differentially expressed genes (DEGs) were identified. The enrichment analysis of discriminant metabolites and lipids reflected alterations in α-linolenic acid and linoleic acid metabolism. Reactome pathway analysis of DEGs revealed a decreased hydroxylation of arachidonic acid in Ccdc80−/− mice. The Kyoto Encyclopedia of Genes and Genomes pathway result suggested a decrease of PPAR signaling and fatty acid degradation by Ccdc80-knockout. The joint pathway analysis integrating metabolomics, lipidomics and transcriptomics indicated that Ccdc80-knockout could down-regulate arachidonic acid and α-linolenic acid metabolism. These results provide new insights into the role of Ccdc80 in fatty acid metabolism.