Oleoyl Serinol

Oleoyl serinol is a gut microbe-derived agonist of GPR119.¹ It stimulates secretion of GLP-1 in vitro (IC₅₀ = 12 µM).² Oleoyl serinol has a variety of meal-related effects in mice, including a reduction of plasma insulin, but not leptin, levels in ad libitum-fed mice and an increase in both plasma insulin and leptin levels in mice fasted for 12 hours, then refed.¹ It alters the circadian oscillations of mouse plasma phosphatidylcholine and ceramide levels in a molecular species-specific manner. Oleoyl serinol (100 µM) also reduces cell viability of F-11 neuroblastoma cells and induces apoptosis in U87 astrocytoma cells.³ At 80 µM, it induces formation of a complex including PAR-4 and PKCζ in embryoid body-derived cells, decreases the levels of the pluripotency marker Oct-4 and prostate apoptosis response-4 (PAR-4), which mediates ceramide-induced apoptosis in embryonic stem cells.⁴

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1. Dutta, S., Mahen, K.K., Massey, W.J., et al. Gut microbe-derived N-acyl serinol lipids shape host postprandial metabolic homeostasis. PNAS 123(12), e2517314123 (2026).

2. Cohen, L.J., Esterhazy, D., Kim, S.H., et al. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature 549(7670), 48-53 (2017).

3. Bieberich, E., Hu, B., Silva, J., et al. Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. Cancer Lett. 181(1), 55-64 (2002).

4. Bieberich, E., Silva, J., Wang, G., et al. Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. J. Cell. Biol. 167(4), 723-734 (2004).