Hepatic Steatosis Accompanies Pulmonary Alveolar Proteinosis

摘要: Maintenance of tissue-specific organ lipid compositions characterizes mammalian homeostasis. The lungs and liver synthesize mixed phosphatidylcholine (PC) molecular species that are subsequently tailored for function. progressively enrich disaturated PC directed to lamellar body surfactant stores before secretion. accumulates polyunsaturated very-low-density lipoprotein assembly secretion, or triglyceride stores. In each tissue, selective enrichment mechanisms lie at the heart effective We tested potential coordination between these spatially separated but possibly complementary phenomena under a major derangement lung metabolism, pulmonary alveolar proteinosis (PAP), which overwhelms homeostasis leads excessive accumulation. Using static dynamic lipidomics techniques, we compared (1) tissue contents, (2) in lungs, absolute rates synthesis both control mice granulocyte-macrophage colony-stimulating factor knockout model PAP. Significant accumulation bronchoalveolar lavage fluid, macrophage, lavaged occurred alongside increased synthesis, consistent with reported defects macrophage turnover. However, microscopy using oil red O staining, coherent anti-Stokes Raman scattering, second harmonic generation, transmission electron also revealed neutral-lipid droplet accumulations lipofibroblasts granular animals, suggesting deficits extend beyond macrophages. PAP plasma composition was significantly fatty acid enriched, content unchanged hepatic acid-enriched by 50% an accompanying micro/macrovesicular steatosis fibrotic damage pattern nonalcoholic disease. These data suggest hepatopulmonary axis metabolism coordination, wider implications understanding managing pathologies compromise one has unexpected consequences another.