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Non-alcoholic fatty liver disease (NAFLD) encompasses a set of pathologies associated with ectopic lipid accumulationin hepatocytes. NAFLD can progress to non-alcoholic steatohepatitis (NASH), an inflammatory condition which is increasing in prevalence in parallel with other diseases connected to lipid metabolism, such as type 2 diabetes and cardiovascular disease. NASH is characterized by hepatic necrosis, increased inflammatory signaling, immune cell infiltration, and the potential to progress to fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately liver failure.

David Montefusco, Maryam Jamil, Melissa A. Maczis, William Schroeder, ... L. Ashley Cowart

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

Ana Rodríguez Sánchez-Archidona, Céline Cruciani-Guglielmacci, Clara Roujeau, Leonore Wigger, ... Bernard Thorens

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 Gckand 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.

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

Ana Rodríguez Sánchez-Archidona, Céline Cruciani-Guglielmacci, Clara Roujeau, Leonore Wigger, ... Bernard Thorens

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 Gckand 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.

2021 impact factor: 8.568

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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