TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S]
Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabol...
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doaj-601aa1aa092d4cf5b188dd0422719c7a2021-04-29T04:34:43ZengElsevierJournal of Lipid Research0022-22752017-06-0158612211229TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S]Giovanni Musso0Ugo Cipolla1Maurizio Cassader2Silvia Pinach3Francesca Saba4Franco De Michieli5Elena Paschetta6Daria Bongiovanni7Luciana Framarin8Nicola Leone9Mara Berrutti10Floriano Rosina11Stefania Corvisieri12Federica Molinaro13Antonio Sircana14Roberto Gambino15To whom correspondence should be addressed.; HUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyMedical Team, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyHUMANITAS Gradenigo, Turin, ItalyEmergency Medicine Department, Sassari Hospital, Sassari, ItalyDepartment of Medical Sciences, University of Turin, Turin, ItalyMechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis. The TM6SF2 T-allele was associated with higher hepatic and adipose insulin resistance, impaired pancreatic β-cell function and incretin effect, and higher muscle insulin sensitivity and whole-body fat oxidation rate. Compared with the TM6SF2 C-allele, the T-allele entailed lower postprandial lipemia and nefaemia, a less atherogenic lipoprotein profile, and a postprandial cholesterol (Chol) redistribution from smaller atherogenic lipoprotein subfractions to larger intestinal and hepatic VLDL1 subfractions. Postprandial plasma VLDL1-Chol response independently predicted the severity of liver histology. In conclusion, the TM6SF2 C>T polymorphism affects nutrient oxidation, glucose homeostasis, and postprandial lipoprotein, adipokine, and GIP responses to fat ingestion independently of fasting values. These differences may contribute to the dual and opposite effect of this polymorphism on liver injury and cardiometabolic risk in NAFLD.http://www.sciencedirect.com/science/article/pii/S0022227520310142nonalcoholic steatohepatitischolesterollipoprotein subfractionslipemianonalcoholic fatty liver diseasetransmembrane 6 superfamily member 2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giovanni Musso Ugo Cipolla Maurizio Cassader Silvia Pinach Francesca Saba Franco De Michieli Elena Paschetta Daria Bongiovanni Luciana Framarin Nicola Leone Mara Berrutti Floriano Rosina Stefania Corvisieri Federica Molinaro Antonio Sircana Roberto Gambino |
spellingShingle |
Giovanni Musso Ugo Cipolla Maurizio Cassader Silvia Pinach Francesca Saba Franco De Michieli Elena Paschetta Daria Bongiovanni Luciana Framarin Nicola Leone Mara Berrutti Floriano Rosina Stefania Corvisieri Federica Molinaro Antonio Sircana Roberto Gambino TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] Journal of Lipid Research nonalcoholic steatohepatitis cholesterol lipoprotein subfractions lipemia nonalcoholic fatty liver disease transmembrane 6 superfamily member 2 |
author_facet |
Giovanni Musso Ugo Cipolla Maurizio Cassader Silvia Pinach Francesca Saba Franco De Michieli Elena Paschetta Daria Bongiovanni Luciana Framarin Nicola Leone Mara Berrutti Floriano Rosina Stefania Corvisieri Federica Molinaro Antonio Sircana Roberto Gambino |
author_sort |
Giovanni Musso |
title |
TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] |
title_short |
TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] |
title_full |
TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] |
title_fullStr |
TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] |
title_full_unstemmed |
TM6SF2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in NAFLD[S] |
title_sort |
tm6sf2 rs58542926 variant affects postprandial lipoprotein metabolism and glucose homeostasis in nafld[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2017-06-01 |
description |
Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis. The TM6SF2 T-allele was associated with higher hepatic and adipose insulin resistance, impaired pancreatic β-cell function and incretin effect, and higher muscle insulin sensitivity and whole-body fat oxidation rate. Compared with the TM6SF2 C-allele, the T-allele entailed lower postprandial lipemia and nefaemia, a less atherogenic lipoprotein profile, and a postprandial cholesterol (Chol) redistribution from smaller atherogenic lipoprotein subfractions to larger intestinal and hepatic VLDL1 subfractions. Postprandial plasma VLDL1-Chol response independently predicted the severity of liver histology. In conclusion, the TM6SF2 C>T polymorphism affects nutrient oxidation, glucose homeostasis, and postprandial lipoprotein, adipokine, and GIP responses to fat ingestion independently of fasting values. These differences may contribute to the dual and opposite effect of this polymorphism on liver injury and cardiometabolic risk in NAFLD. |
topic |
nonalcoholic steatohepatitis cholesterol lipoprotein subfractions lipemia nonalcoholic fatty liver disease transmembrane 6 superfamily member 2 |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520310142 |
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