Mechanistic insights into the lipid-lowering effects of phycocyanin through human intestinal and liver organoids

, improves hyperlipidemia in vivo; however, its mechanisms remain elusive. This study investigated whether PC influences lipid metabolism, particularly lipoprotein secretion dynamics, using human small intestine and liver organoids, which are physiologically relevant in vitro models. In small intestinal organoids, PC significantly suppressed chylomicron marker apolipoprotein (Apo) B-48 secretion without affecting its expression and intracellular triglyceride levels. Peptidomic analysis using mass spectrometry identified MKTPL as a key peptide among digestion-derived peptides of PC that exhibited an inhibitory effect on chylomicron secretion similar to that of intact PC. In liver organoids, digested PC (dPC) and MKTPL reduced the secretion of very-low-density lipoprotein marker ApoB-100. These results revealed the novel action of PC and dPC in preventing lipoprotein secretion in both intestinal and liver cells, providing mechanistic insights into their lipid-lowering effects.