Introduction: The prevalence of glycolipid metabolism disorder continues to increase globally and has become a serious threat to human health. Multi-omics provide unprecedented insights into the underlying pathophysiological mechanisms of glycolipid metabolism disorder and identifying potential biomarkers and therapeutic targets.
Methods: We collected blood/stool samples from 30 patients with type 2 diabetes and dyslipidemia (GL), 30 patients with hyperlipidemia (HL), and 30 healthy controls, conducted transcriptome/proteome/metabolome/microbiome analysis, and correlated it with clinical phenotypes. We further integrated multi-omics features and tested the discriminant efficacy of multi-omics datasets using receiver operating characteristic curves.
Results: Among patients with GL, insulin like growth factor binding protein 3 (IGFBP3) in the p53 signaling pathway was highly expressed at both the transcription and protein levels. Joint analysis of proteomics and metabolomics confirmed the link between fructose-bisphosphate aldolase B and altered N-acetylornithine metabolism in the amino acid biosynthetic pathway. The gut microbiota dysbiosis in patients with GL was characterized by a significantly reduced abundance of short-chain fatty acids-producing bacteria, and this reduction was related to a decrease in dodecanoic acid. The extracellular matrix-receptor interaction pathway was associated with HL, and collagen type I alpha 1 chain in this pathway was lowly expressed at both the transcription and protein levels. The abundance of Parabacteroides gordonii was significantly reduced in patients with HL. Matrix metallopeptidase 2 and IGFBP3, key differential molecules between GL and HL, were highly expressed at both the transcription and protein levels.
Conclusion: This study revealed the multi-omics signature and key drivers of glycolipid metabolism disorder.
X. Fang: None. R. Miao: None. H. Wu: None. Y. Zhang: None. J. Tian: None.
Capital Health Development Research Project (CD2020-4-4155); CACMS Outstanding Young Scientific and Technological Talents Program (ZZ13-YQ-026); Scientific and technological innovation project of China Academy of Chinese Medical Sciences (CI2021A01601); Open Project of National Facility for Translational Medicine (TMSK-2021-407); CACMS Guang'anmen Hospital Sustainability Project-Young Top-Notch Talent Project (NO.CZ40907).
