We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes.
- Authors
Willeit, Peter; Skroblin, Philipp; Moschen, Alexander R.; Xiaoke Yin; 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; Yin, Xiaoke
- 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-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.
- Subjects
MICRORNA; ATORVASTATIN; METABOLIC disorders; INSULIN resistance; OBESITY; DRUG therapy for hyperlipidemia; RNA metabolism; ANIMALS; ANTILIPEMIC agents; CARRIER proteins; COMPLEMENT (Immunology); EPITHELIAL cells; GENETIC disorders; GLYCOPROTEINS; HYPERLIPIDEMIA; IMMUNOBLOTTING; LIPID metabolism disorders; LIPOPROTEINS; LONGITUDINAL method; MASS spectrometry; MICE; MULTIVARIATE analysis; TYPE 2 diabetes; NUCLEOTIDES; NUCLEOTIDE separation; POLYMERASE chain reaction; RESEARCH funding; RNA; SERUM albumin; METABOLIC syndrome; DISEASE incidence; DISEASE prevalence; REVERSE transcriptase polymerase chain reaction; PHARMACODYNAMICS
- Publication
Diabetes, 2017, Vol 66, Issue 2, p347
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db16-0731