期刊
DIABETES
卷 66, 期 2, 页码 347-357出版社
AMER DIABETES ASSOC
DOI: 10.2337/db16-0731
关键词
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资金
- Erwin Schrodinger Fellowship
- Austrian Science Fund [J-3679-B13]
- Studienstiftung des Deutschen Volkes
- American Heart Association [15SDG23000025]
- National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre
- British Heart Foundation special project grant [SP/12/5/29574]
- Fondation Leducq (MIRVAD) [13 CVD 02]
- Diabetes UK [12/0004530]
- Austrian Research Promotion Agency FFG (Research Center of Excellence in Vascular Ageing Tyrol, VASCage) [843536]
- Pustertaler Verein zur Pravention von Herz- und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck
- Assessorat fur Gesundheit, Province of Bolzano, Italy
- JDRF
- NIHR Biomedical Research Center based at Guy's and St Thomas' National Health Service Foundation Trust
- King's College London in partnership
- King's College Hospital
- National Institutes of Health [R01HL107953, 1F31AG043318, R01HL106063]
- Foundation Leducq Transatlantic Network of Excellence in Cardiovascular Research
- Austrian Science Fund (FWF) [J 3679] Funding Source: researchfish
- British Heart Foundation [FS/13/18/30207, FS/13/2/29892, SP/12/5/29574, RG/16/14/32397] Funding Source: researchfish
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-alpha-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing mono-unsaturated 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.
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