Plasma triacylglycerols are biomarkers of ß-cell function in mice and humans
| Autor: | Bernard Thorens, Michele Solimena, Christian Klose, Jürgen Weitz, Florence Mehl, Jessica Denom, Ana Rodriguez Sanchez-Archidona, Clara Roujeau, Mark Ibberson, Christophe Magnan, Marko Barovic, Céline Cruciani-Guglielmacci, Kai Simons, Nadim Kassis, Leonore Wigger, Marius Distler, Justine Lallement |
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| Rok vydání: | 2021 |
| Předmět: |
Male
PC phosphatidylcholines HFD high-fat diet T2D Type 2 diabetes medicine.medical_treatment PITPNC1 Type 2 diabetes Transcriptome Mice AUC area under the curve LPC lysophosphatidylcholines 0302 clinical medicine Insulin-Secreting Cells Gene expression Insulin Secretion Internal medicine Cells Cultured 0303 health sciences Mice Inbred BALB C geography.geographical_feature_category Chol cholesterol OXPHOS Oxidative phosphorylation ABHD6 Islet Cell biology Mice Inbred DBA TAGs triacylglycerols VDR vitamin D receptor Original Article Sphingomyelin Systems biology medicine.drug LDL low-density lipoproteins β-cell function 030209 endocrinology & metabolism Biology GSIS glucose-stimulated insulin secretion ER endoplasmic reticulum 03 medical and health sciences SMs sphingomyelins WGCNA weighted gene co-expression network analysis GO Gene Ontology medicine KEGG Kyoto encyclopedia of genes and genomes Animals Humans Lpl lipoprotein lipase Carnitine PI phosphatidylinositols Molecular Biology Triglycerides 030304 developmental biology geography PCA principal component analysis HDL high-density lipoproteins Insulin RC regular chow Cell Biology medicine.disease RC31-1245 CE cholesteryl esters Mice Inbred C57BL Biomarkers/blood Biomarkers/metabolism Glucose/metabolism Insulin-Secreting Cells/metabolism Triglycerides/blood Triglycerides/metabolism Biomarkers Triacylglycerols Glucose |
| Zdroj: | Molecular Metabolism Molecular metabolism, vol. 54, pp. 101355 Molecular Metabolism, Vol 54, Iss, Pp 101355-(2021) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2021.101355 |
| Popis: | 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. Highlights • Plasma triacylglycerols correlated with genes controlling β-cell mass and function. • Plasma triacylglycerols correlated with genes controlling liver β-oxidation. • In humans, triacylglycerols also correlated with key regulators of insulin secretion. • Mouse and human data identified PITPNC1 as a candidate regulator of insulin secretion. • Triacylglycerols are biomarkers of the liver-to-β-cell axis and β-cell function. |
| Databáze: | OpenAIRE |
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