Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis - PubMed
12 hours ago
- #MASH
- #Multiomics
- #Atherosclerosis
- Sex-based multiomics analysis identifies metabolic and molecular mediators linking MASH and atherosclerosis.
- Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in MASH patients, with no current therapy targeting both diseases.
- Male and female Ldlr -/- mice were fed different diets to study concurrent MASH and atherosclerosis.
- Modified choline-deficient high-fat diet (mCDHFD) induced MASH-fibrosis in both sexes, while western diet (WD) was effective only in males.
- Circulating cholesterol and CCL2 were identified as potential predictors of coexisting disease.
- Key dysregulated pathways include arginine-proline, glycine-serine, glutathione, and sphingolipid metabolism.
- Sphinganine emerged as a predictor of disease severity.
- Hepatic itaconate and lactate levels positively correlated with disease severity, while glycine, carnitine, 2-aminomuconic acid, and thiamine pyrophosphate were negatively associated.
- Lipidomic analyses revealed dysregulated polyunsaturated fatty acid, steryl ester, and dihexosylceramide metabolism.
- Mouse and human transcriptomes showed similarities in metabolic and proinflammatory/proatherogenic pathways.
- The study establishes a murine model of concurrent MASH and atherosclerosis and identifies sex-specific dietary responses and pathways.