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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2017
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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 |
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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 |
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