Plasma triacylglycerols are biomarkers of β-cell function in mice and humans

Objectives: To find plasma biomarkers prognostic of type 2 diabetes, which could also inform on pancreatic β-cell deregulations or defects in the function of insulin target tissues. Methods: We conducted a systems biology approach to characterize the plasma lipidomes of C57Bl/6J, DBA/2J, and BALB/cJ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ana Rodríguez Sánchez-Archidona, Céline Cruciani-Guglielmacci, Clara Roujeau, Leonore Wigger, Justine Lallement, Jessica Denom, Marko Barovic, Nadim Kassis, Florence Mehl, Jurgen Weitz, Marius Distler, Christian Klose, Kai Simons, Mark Ibberson, Michele Solimena, Christophe Magnan, Bernard Thorens
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Triacylglycerols β-cell function Systems biology Type 2 diabetes PITPNC1 Biomarkers Internal medicine RC31-1245
Acceso en línea:	https://doaj.org/article/477a61cb926a45169eb295d1b2333bc1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:477a61cb926a45169eb295d1b2333bc1
record_format	dspace
spelling	oai:doaj.org-article:477a61cb926a45169eb295d1b2333bc12021-11-12T04:32:35ZPlasma triacylglycerols are biomarkers of β-cell function in mice and humans2212-877810.1016/j.molmet.2021.101355https://doaj.org/article/477a61cb926a45169eb295d1b2333bc12021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2212877821002027https://doaj.org/toc/2212-8778Objectives: To find plasma biomarkers prognostic of type 2 diabetes, which could also inform on pancreatic β-cell deregulations or defects in the function of insulin target tissues. Methods: We conducted a systems biology approach to characterize the plasma lipidomes of C57Bl/6J, DBA/2J, and BALB/cJ mice under different nutritional conditions, as well as their pancreatic islet and liver transcriptomes. We searched for correlations between plasma lipids and tissue gene expression modules. Results: We identified strong correlation between plasma triacylglycerols (TAGs) and islet gene modules that comprise key regulators of glucose- and lipid-regulated insulin secretion and of the insulin signaling pathway, the two top hits were Gck and Abhd6 for negative and positive correlations, respectively. Correlations were also found between sphingomyelins and islet gene modules that overlapped in part with the gene modules correlated with TAGs. In the liver, the gene module most strongly correlated with plasma TAGs was enriched in mRNAs encoding fatty acid and carnitine transporters as well as multiple enzymes of the β-oxidation pathway. In humans, plasma TAGs also correlated with the expression of several of the same key regulators of insulin secretion and the insulin signaling pathway identified in mice. This cross-species comparative analysis further led to the identification of PITPNC1 as a candidate regulator of glucose-stimulated insulin secretion. Conclusion: TAGs emerge as biomarkers of a liver-to-β-cell axis that links hepatic β-oxidation to β-cell functional mass and insulin secretion.Ana Rodríguez Sánchez-ArchidonaCéline Cruciani-GuglielmacciClara RoujeauLeonore WiggerJustine LallementJessica DenomMarko BarovicNadim KassisFlorence MehlJurgen WeitzMarius DistlerChristian KloseKai SimonsMark IbbersonMichele SolimenaChristophe MagnanBernard ThorensElsevierarticleTriacylglycerolsβ-cell functionSystems biologyType 2 diabetesPITPNC1BiomarkersInternal medicineRC31-1245ENMolecular Metabolism, Vol 54, Iss , Pp 101355- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Triacylglycerols β-cell function Systems biology Type 2 diabetes PITPNC1 Biomarkers Internal medicine RC31-1245
spellingShingle	Triacylglycerols β-cell function Systems biology Type 2 diabetes PITPNC1 Biomarkers Internal medicine RC31-1245 Ana Rodríguez Sánchez-Archidona Céline Cruciani-Guglielmacci Clara Roujeau Leonore Wigger Justine Lallement Jessica Denom Marko Barovic Nadim Kassis Florence Mehl Jurgen Weitz Marius Distler Christian Klose Kai Simons Mark Ibberson Michele Solimena Christophe Magnan Bernard Thorens Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
description	Objectives: To find plasma biomarkers prognostic of type 2 diabetes, which could also inform on pancreatic β-cell deregulations or defects in the function of insulin target tissues. Methods: We conducted a systems biology approach to characterize the plasma lipidomes of C57Bl/6J, DBA/2J, and BALB/cJ mice under different nutritional conditions, as well as their pancreatic islet and liver transcriptomes. We searched for correlations between plasma lipids and tissue gene expression modules. Results: We identified strong correlation between plasma triacylglycerols (TAGs) and islet gene modules that comprise key regulators of glucose- and lipid-regulated insulin secretion and of the insulin signaling pathway, the two top hits were Gck and Abhd6 for negative and positive correlations, respectively. Correlations were also found between sphingomyelins and islet gene modules that overlapped in part with the gene modules correlated with TAGs. In the liver, the gene module most strongly correlated with plasma TAGs was enriched in mRNAs encoding fatty acid and carnitine transporters as well as multiple enzymes of the β-oxidation pathway. In humans, plasma TAGs also correlated with the expression of several of the same key regulators of insulin secretion and the insulin signaling pathway identified in mice. This cross-species comparative analysis further led to the identification of PITPNC1 as a candidate regulator of glucose-stimulated insulin secretion. Conclusion: TAGs emerge as biomarkers of a liver-to-β-cell axis that links hepatic β-oxidation to β-cell functional mass and insulin secretion.
format	article
author	Ana Rodríguez Sánchez-Archidona Céline Cruciani-Guglielmacci Clara Roujeau Leonore Wigger Justine Lallement Jessica Denom Marko Barovic Nadim Kassis Florence Mehl Jurgen Weitz Marius Distler Christian Klose Kai Simons Mark Ibberson Michele Solimena Christophe Magnan Bernard Thorens
author_facet	Ana Rodríguez Sánchez-Archidona Céline Cruciani-Guglielmacci Clara Roujeau Leonore Wigger Justine Lallement Jessica Denom Marko Barovic Nadim Kassis Florence Mehl Jurgen Weitz Marius Distler Christian Klose Kai Simons Mark Ibberson Michele Solimena Christophe Magnan Bernard Thorens
author_sort	Ana Rodríguez Sánchez-Archidona
title	Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
title_short	Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
title_full	Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
title_fullStr	Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
title_full_unstemmed	Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
title_sort	plasma triacylglycerols are biomarkers of β-cell function in mice and humans
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/477a61cb926a45169eb295d1b2333bc1
work_keys_str_mv	AT anarodriguezsanchezarchidona plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT celinecrucianiguglielmacci plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT clararoujeau plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT leonorewigger plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT justinelallement plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT jessicadenom plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT markobarovic plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT nadimkassis plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT florencemehl plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT jurgenweitz plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT mariusdistler plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT christianklose plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT kaisimons plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT markibberson plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT michelesolimena plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT christophemagnan plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans AT bernardthorens plasmatriacylglycerolsarebiomarkersofbcellfunctioninmiceandhumans
_version_	1718431287253925888

Plasma triacylglycerols are biomarkers of β-cell function in mice and humans

Ejemplares similares