The Journal of nutrition · 2026
Provision of Lauric Acid Results in Endogenous Production of the Liver Receptor Homolog-1 Ligand, Dilauroylphosphatidylcholine, and Evidence of LRH-1 Transactivation.
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Klatt Kevin C, Fontenot Lindsey, Dong Bingning, Patel Pooja, Malysheva Olga V, Brenna J Thomas, Roberson Mark S, Hartig Sean M, Caudill Marie A, Moore David D
Аннотация
BACKGROUND: The unusual phosphatidylcholine species dilauroylphosphatidylcholine (DLPC) has been reported to bind and activate the orphan nuclear receptor liver receptor homolog-1 (LRH-1). To date, DLPC has not been reported endogenously.
OBJECTIVE: Herein, we test the hypothesis that the provision of the acyl constituent of DLPC, lauric acid (C12:0), a saturated fatty acid rich in coconut oil, will 1) result in endogenous DLPC production and 2) enhance LRH-1 transcriptional activity.
METHODS: We measured DLPC following provision of C12:0 to HepG2 cells, C57/BL6J mice, and to healthy human participants in an acute, randomized, controlled crossover trial. LRH-1fl/fl and LRH-1fl/fl Albumin-Cre mice were used in ex vivo and in vivo approaches to assess the impact of C12:0 on LRH-1 target gene expression. Methyl-d9-choline was used to assess DLPC production dynamics.
RESULTS: DLPC was not observed in any C12:0-free system. Provision of C12:0 in the culture media or to C57/BL6J mice resulted in the rapid accumulation of DLPC, including DLPC's presence in multiple LRH-1 expressing tissues. Coconut oil-fed human participants exhibited DLPC in postprandial serum samples. Ex vivo and in vivo C12:0 provision resulted in increased mRNA expression of LRH-1 target gene(s), an effect that was not observed in hepatic knockout mice. Methyl-d9-choline administration revealed a complex reliance on CDP-choline-derived DLPC.
CONCLUSION: C12:0 provision results in endogenous production of the LRH-1 ligand DLPC and LRH-1 transcriptional activation phenotypes. Our findings highlight potential pleiotropic effects of lauric acid, a common hypercholesterolemic dietary saturated fatty acid, secondary to LRH-1 agonism.
TRIAL REGISTRATION: NCT03481608.
OBJECTIVE: Herein, we test the hypothesis that the provision of the acyl constituent of DLPC, lauric acid (C12:0), a saturated fatty acid rich in coconut oil, will 1) result in endogenous DLPC production and 2) enhance LRH-1 transcriptional activity.
METHODS: We measured DLPC following provision of C12:0 to HepG2 cells, C57/BL6J mice, and to healthy human participants in an acute, randomized, controlled crossover trial. LRH-1fl/fl and LRH-1fl/fl Albumin-Cre mice were used in ex vivo and in vivo approaches to assess the impact of C12:0 on LRH-1 target gene expression. Methyl-d9-choline was used to assess DLPC production dynamics.
RESULTS: DLPC was not observed in any C12:0-free system. Provision of C12:0 in the culture media or to C57/BL6J mice resulted in the rapid accumulation of DLPC, including DLPC's presence in multiple LRH-1 expressing tissues. Coconut oil-fed human participants exhibited DLPC in postprandial serum samples. Ex vivo and in vivo C12:0 provision resulted in increased mRNA expression of LRH-1 target gene(s), an effect that was not observed in hepatic knockout mice. Methyl-d9-choline administration revealed a complex reliance on CDP-choline-derived DLPC.
CONCLUSION: C12:0 provision results in endogenous production of the LRH-1 ligand DLPC and LRH-1 transcriptional activation phenotypes. Our findings highlight potential pleiotropic effects of lauric acid, a common hypercholesterolemic dietary saturated fatty acid, secondary to LRH-1 agonism.
TRIAL REGISTRATION: NCT03481608.