Lipid dysregulation in chronic diseases: systems biology and omics perspectives

1. Lipids are fundamental regulators of cellular structure, energy balance, and signalling, while their dysregulation contributes significantly to the development of chronic diseases.

2. Recent advances in multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, have transformed the investigation of lipid metabolism by enabling high-resolution characterisation of lipid species, metabolic pathways, and regulatory networks.

3. This review emphasises the significance of lipids in chronic metabolic diseases like cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver disease, neurodegenerative disorders, cancer, and chronic kidney disease.

4. The discovery of various biomarkers of disease conditions via lipidomics analysis includes lipids such as ceramides, oxidised phospholipids, acylcarnitines, and lysophospholipids, which have been implicated in causing inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis.

5. Omics integration can aid in obtaining new perspectives in understanding disease pathophysiology and help in identifying novel therapeutic targets including PCSK9 (Proprotein convertase subtilisin/kexin type 9), ANGPTL3 (Angiopoietin-like 3), and inflammatory lipids. Recent lipidomics platforms like spatial lipidomics and single-cell lipidomics may add value in developing personalised medicine therapies.