Stepwise pancreatic β-cell differentiation protocols, designed to recapitulate key developmental milestones of pancreatic organogenesis—from def

Acute elevation in circulating lipids induces reversible insulin resistance and alters triglyceride-rich lipoprotein flux. Whether insulin-regulated remodelling of high-density lipoprotein (HDL)-associated apolipoproteins is altered during defined lipid stress in women with polyendocrine metabolic ovarian syndrome (PMOS) remains unclear. In this exploratory, randomized, cross-over study, 10 healthy women and 12 women with PMOS underwent 5-h saline or lipid infusion, with a hyperinsulinemic–euglycemic clamp commencing at 180 min. Plasma proteomics were performed at baseline, 180 min and 300 min using linear modelling (limma). Lipid infusion induced the coordinated suppression of ApoA1 and ApoE isoforms at 180 min in both groups (FDR-adjusted p < 0.01), followed by partial recovery during hyperinsulinemia. Women with PMOS exhibited greater early suppression of ApoA1 (log₂ fold-change −2.20, p = 0.001) and more persistent suppression of ApoE isoforms at 300 min (ApoE3 log₂ −1.64, p = 0.001). ApoA1 suppression correlated inversely with NEFA exposure during lipid infusion (Spearman ρ = −0.54, p = 0.021). Controlled lipid challenge reveals amplified but reversible dysregulation of HDL-associated apolipoproteins in PMOS, with the preservation of the overall response pattern, but impaired recovery under hyperinsulinemic conditions. These findings suggest impaired adaptation to acute lipid stress in PMOS, with ApoA1 changes appearing to relate more closely to acute NEFA exposure than to clamp-derived insulin sensitivity.