Comparative study of palmitoleic acid, sea buckthorn oil, and lovastatin in hepatocellular steatosis model.

Palmitoleic acid (POA) has been associated with various metabolic effects, including regulating lipid metabolism and cholesterol production. In this study, we explored the impact of both cis- (cPOA) and trans-palmitoleic acid (tPOA), along with sea buckthorn oil (SBO), a natural source rich in cPOA, on lipid content, metabolic activity, and Rap1 prenylation in HepG2 cells. We employed a free fatty acids-induced steatosis model. Our findings revealed that neither cPOA, tPOA, SBO, nor digested SBO impaired the metabolic activity of HepG2 cells, even under steatotic conditions. All treatments led to triacylglycerol (TAG) accumulation, with tPOA demonstrating the beneficial effect. While cholesterol levels remained unchanged in normal cells, a reduction was noted in steatotic cells, comparable to the effect of lovastatin. Molecular docking suggested that both POA isomers may bind and block the catalytic pocket of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). To further explore this, we examined their influence on Rap1 prenylation and subcellular localization. Under steatotic conditions, both POA isomers, particularly at concentrations of 50 and 100 µM, elevated cytosolic Rap1 levels, whereas no significant changes were observed in membrane or cytosolic Rap1a protein levels in normal HepG2 cultures. Notably, unlike lovastatin, POA isomers and digested SBO enhanced glucose-stimulated insulin secretion from pancreatic cells. Our results highlight the potential of POA isomers and SBO as modulators of lipid metabolism, cholesterol production, and insulin secretion, suggesting their relevance in managing metabolic disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37006-y.