Maintenance of tissue-specific organ lipid compositions characterises mammalian lipid homeostasis. Lung and liver synthesise mixed phosphatidylcholine (PC) molecular species subsequently "tailored" for function. Lungs progressively enrich disaturated PC (DSPC) directed to lamellar body (LB) surfactant stores prior to secretion. Liver accumulates polyunsaturated PC directed to VLDL assembly and secretion, or triglyceride stores. In each tissue, selective PC species enrichment mechanisms lie at the heart of effective homeostasis. We tested potential coordination between these spatially separated, but possibly complementary phenomena under a major derangement of lung PC metabolism, Pulmonary Alveolar Proteinosis (PAP), which overwhelms homeostasis leading to excessive surfactant accumulation. Using static and dynamic lipidomics techniques we compared (i) tissue PC compositions and contents and (ii) in lungs, the absolute rates of synthesis from both control mice and the GM-CSF knockout model of PAP. Significant DSPC accumulation in BALF, Alveolar Macrophage (AM) and lavaged lung tissue occurred alongside increased PC synthesis consistent with reported defects in AM surfactant turnover. However, microscopy using oil red O staining, CARS, SHG and TEM also revealed neutral lipid droplet accumulations in alveolar lipofibroblasts of GM-CSF KO animals suggesting lipid homeostasis deficits extend beyond AMs. PAP plasma PC composition was significantly PUFA-enriched but content was unchanged and hepatic PUFA-enriched PC content increased by 50% with an accompanying micro/macrovesicular steatosis and a fibrotic damage pattern consistent with NAFLD. These data suggest a hepato-pulmonary axis of PC metabolism coordination with wider implications for understanding and managing lipid pathologies where compromise of one organ has unexpected consequences for another.