Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge

Abstract

Postprandial lipemia has many physiopathological effects, some of which increase the risk of cardiovascular disease. MicroRNAs (miRNAs) can be found in almost all biological fluids, but their postprandial kinetics are poorly described. We aimed to profile circulating miRNAs in response to a fat challenge. In total, 641 circulating miRNAs were assessed by real-time PCR in plasmas from mice two hours after lipid gavage. Mice with intestine-specific loss of Dicer were screened to identify potential miRNAs released by the intestine. A total of 68 miRNAs were selected for further validation. Ten circulating miRNAs were finally validated as responsive to postprandial lipemia, including miR-206-3p, miR-543-3p, miR-466c-5p, miR-27b-5p, miR-409-3p, miR-340-3p, miR-1941-3p, miR-10a-3p, miR-125a-3p, and miR-468-3p. Analysis of their possible tissues of origin/target showed an enrichment of selected miRNAs in liver, intestine, brain, or skeletal muscle. miR-206, miR-27b-5p, and miR-409-3p were validated in healthy humans. Analysis of their predicted target genes revealed their potential involvement in insulin/insulin like growth factor (insulin/IGF), angiogenesis, cholecystokinin B receptor signaling pathway (CCKR), inflammation or Wnt pathways for mice, and in platelet derived growth factor (PDGF) and CCKR signaling pathways for humans. Therefore, the current study shows that certain miRNAs are released in the circulation in response to fatty meals, proposing them as potential novel therapeutic targets of lipid metabolism.

This research was funded by grants from the Fundación Ramón Areces (CIVP18A3888) to A.D., F.V., J.T.-C., M.C.C., J.G.-Z. and R.M.-H.; by the Spanish “Agencia Estatal de Investigación” to A.D. and R.M.-H. (AGL2016-78922-R) and to M.A.L. (SAF2015-70747-R). Also supported by Fondo Europeo de Desarrollo Regional (FEDER) European funds. This research was also supported by the Nicolas Monardes program (C-0032-2016) from Consejería de Salud, co-funded by FEDER European funds (Madrid, Spain) to F.C. Also supported by grant PI17/01104 from the Instituto de Salud Carlos III to F. C.; and partly funded by POR FESR 3S4H to F.V. D.C.M.-E. is a fellow of “Centro de Estudios Interdisciplinarios Básicos y Aplicados” (CEIBA), Colombia, through the program “Bolívar Gana con Ciencia”. M.-C.L.d.l.H and L.d.P.-A were recipients of a contract supported by Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid, Fondo Social Europeo, and Iniciativa de Empleo Juvenil YEI (PEJD-2016/BIO-2781 and PEJD-2017-PRE/BIO-5100, respectively). A.G.-R. acknowledges the Marie Curie AMAROUT-II Europe Program (Grant Agreement No. 291803). We would also like to thank the COST Action CA16120 Epitran for networking.