Cargando…

Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes

MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulatin...

Descripción completa

Detalles Bibliográficos
Autores principales: Willeit, Peter, Skroblin, Philipp, Moschen, Alexander R., Yin, Xiaoke, Kaudewitz, Dorothee, Zampetaki, Anna, Barwari, Temo, Whitehead, Meredith, Ramírez, Cristina M., Goedeke, Leigh, Rotllan, Noemi, Bonora, Enzo, Hughes, Alun D., Santer, Peter, Fernández-Hernando, Carlos, Tilg, Herbert, Willeit, Johann, Kiechl, Stefan, Mayr, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248985/
https://www.ncbi.nlm.nih.gov/pubmed/27899485
http://dx.doi.org/10.2337/db16-0731
_version_ 1782497365548072960
author Willeit, Peter
Skroblin, Philipp
Moschen, Alexander R.
Yin, Xiaoke
Kaudewitz, Dorothee
Zampetaki, Anna
Barwari, Temo
Whitehead, Meredith
Ramírez, Cristina M.
Goedeke, Leigh
Rotllan, Noemi
Bonora, Enzo
Hughes, Alun D.
Santer, Peter
Fernández-Hernando, Carlos
Tilg, Herbert
Willeit, Johann
Kiechl, Stefan
Mayr, Manuel
author_facet Willeit, Peter
Skroblin, Philipp
Moschen, Alexander R.
Yin, Xiaoke
Kaudewitz, Dorothee
Zampetaki, Anna
Barwari, Temo
Whitehead, Meredith
Ramírez, Cristina M.
Goedeke, Leigh
Rotllan, Noemi
Bonora, Enzo
Hughes, Alun D.
Santer, Peter
Fernández-Hernando, Carlos
Tilg, Herbert
Willeit, Johann
Kiechl, Stefan
Mayr, Manuel
author_sort Willeit, Peter
collection PubMed
description MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-α-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids. Proteomics analysis of livers from antagomiR-122–treated mice revealed novel regulators of hepatic lipid metabolism that are responsive to miR-122 inhibition. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT, n = 155), 12-month atorvastatin reduced circulating miR-122. A similar response to atorvastatin was observed in mice and cultured murine hepatocytes. Over up to 15 years of follow-up in the Bruneck Study, multivariable adjusted risk ratios per one-SD higher log miR-122 were 1.60 (95% CI 1.30–1.96; P < 0.001) for metabolic syndrome and 1.37 (1.03–1.82; P = 0.021) for type 2 diabetes. In conclusion, circulating miR-122 is strongly associated with the risk of developing metabolic syndrome and type 2 diabetes in the general population.
format Online
Article
Text
id pubmed-5248985
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-52489852017-08-01 Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes Willeit, Peter Skroblin, Philipp Moschen, Alexander R. Yin, Xiaoke Kaudewitz, Dorothee Zampetaki, Anna Barwari, Temo Whitehead, Meredith Ramírez, Cristina M. Goedeke, Leigh Rotllan, Noemi Bonora, Enzo Hughes, Alun D. Santer, Peter Fernández-Hernando, Carlos Tilg, Herbert Willeit, Johann Kiechl, Stefan Mayr, Manuel Diabetes Metabolism MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-α-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids. Proteomics analysis of livers from antagomiR-122–treated mice revealed novel regulators of hepatic lipid metabolism that are responsive to miR-122 inhibition. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT, n = 155), 12-month atorvastatin reduced circulating miR-122. A similar response to atorvastatin was observed in mice and cultured murine hepatocytes. Over up to 15 years of follow-up in the Bruneck Study, multivariable adjusted risk ratios per one-SD higher log miR-122 were 1.60 (95% CI 1.30–1.96; P < 0.001) for metabolic syndrome and 1.37 (1.03–1.82; P = 0.021) for type 2 diabetes. In conclusion, circulating miR-122 is strongly associated with the risk of developing metabolic syndrome and type 2 diabetes in the general population. American Diabetes Association 2017-02 2016-11-29 /pmc/articles/PMC5248985/ /pubmed/27899485 http://dx.doi.org/10.2337/db16-0731 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Metabolism
Willeit, Peter
Skroblin, Philipp
Moschen, Alexander R.
Yin, Xiaoke
Kaudewitz, Dorothee
Zampetaki, Anna
Barwari, Temo
Whitehead, Meredith
Ramírez, Cristina M.
Goedeke, Leigh
Rotllan, Noemi
Bonora, Enzo
Hughes, Alun D.
Santer, Peter
Fernández-Hernando, Carlos
Tilg, Herbert
Willeit, Johann
Kiechl, Stefan
Mayr, Manuel
Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title_full Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title_fullStr Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title_full_unstemmed Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title_short Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes
title_sort circulating microrna-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248985/
https://www.ncbi.nlm.nih.gov/pubmed/27899485
http://dx.doi.org/10.2337/db16-0731
work_keys_str_mv AT willeitpeter circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT skroblinphilipp circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT moschenalexanderr circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT yinxiaoke circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT kaudewitzdorothee circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT zampetakianna circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT barwaritemo circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT whiteheadmeredith circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT ramirezcristinam circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT goedekeleigh circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT rotllannoemi circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT bonoraenzo circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT hughesalund circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT santerpeter circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT fernandezhernandocarlos circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT tilgherbert circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT willeitjohann circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT kiechlstefan circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes
AT mayrmanuel circulatingmicrorna122isassociatedwiththeriskofnewonsetmetabolicsyndromeandtype2diabetes