King's College London

Research portal

Circulating MicroRNA-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes

Research output: Contribution to journalArticle

Peter Willeit, Philipp Skroblin, Alexander R. Moschen, Xiaoke Yin, Dorothee Kaudewitz, Anna Zampetaki, Temo Barwari, Meredith Whitehead, Cristina M. Ramírez, Leigh Goedeke, Noemi Rotllan, Enzo Bonora, Alun D. Hughes, Peter Santer, Carlos Fernández-Hernando, Herbert Tilg, Johann Willeit, Stefan Kiechl, Manuel Mayr

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalDiabetes
Volume66
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

King's Authors

Abstract

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-a-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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454