Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS - PubMed
8 hours ago
- #Lipid Metabolism
- #ALS
- #Hypothalamus
- Disruption of the angiopoietin-like protein (ANGPTL) system links lipid metabolism and hypothalamic dysfunction in ALS.
- Alterations in lipid metabolism, including changes in triglycerides and cholesterol, are observed in ALS patients and pre-symptomatic gene carriers.
- Study analyzed serum samples from ALS patients and controls, revealing mutation-specific lipid abnormalities correlated with reduced ANGPTL-3 and -4 levels.
- ANGPTL-3/4 levels correlate with hypothalamic atrophy but not corticospinal involvement, as shown by MRI volumetry and diffusion tensor imaging.
- Findings in human patients were recapitulated in SOD1 murine ALS models, showing repartitioning of lipid utilization from muscles to brown adipose tissue.
- Systemic ANGPTL-3 levels correlate with hypothalamic neuroinflammation, vascular permeability, and levels of agouti-related protein and neuropeptide Y.
- The study provides a molecular mechanism connecting peripheral lipid metabolism to hypothalamic dysfunction via ANGPTL-3 and -4, offering potential therapeutic targets.