Work

Integrating multi-omics to reveal the molecular mechanism of lipid metabolism regulated by a splice variant of Lysyl-oxidase like-2, LOXL2Δ13

Year: 2025

Type: article

Abstract: LOXL2Δ13, a splice variant of Lysyl-oxidase like-2 (LOXL2), enhances glucose metabolism and induces adipose depletion in mice. The precise role of LOXL2Δ13 in lipid metabolism is unclear. Through multi-omics integration, we analyzed the transcriptome, metabolome, proteome, and protein modifications profiles in LOXL2Δ13 overexpression mice. Molecular dynamics simulation and interaction mass spectrometry confirmed key biomarkers influenced by LOXL2Δ13. Here, LOXL2Δ13 was found to cause diglyceride and glycerophospholipid accumulation and alter kinase activities in pathways. Differentially expressed genes, proteins, and metabolites were enriched in lipid metabolism pathways, indicating LOXL2Δ13 influences metabolic enzyme activity by regulating protein expression and modifications. Further immunoprecipitation assay demonstrated that four proteins (Itpr1, Acat1, Canx, and Pdia3) directly interact with LOXL2∆13. This suggests that LOXL2∆13 can regulate lipid metabolic pathways through direct interactions affecting the activity of these key proteins, which in turn induce alterations in their phosphorylation or acetylation modifications, thereby affecting the lipid metabolic pathways. Integrating transcriptomic, metabolomic, proteomic, and protein modification profiles reveals that LOXL2Δ13 modulates metabolic enzyme activity by regulating protein expression and modifications, thereby influencing lipid metabolism pathways.

Source: Communications Biology

DOI: 10.1038/s42003-025-09199-x