Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes.
Peter WilleitPhilipp SkroblinAlexander R MoschenXiaoke YinDorothee KaudewitzAnna ZampetakiTemo BarwariMeredith WhiteheadCristina M RamírezLeigh GoedekeNoemi RotllanEnzo BonoraAlun D HughesPeter SanterCarlos Fernández-HernandoHerbert TilgJohann WilleitStefan KiechlManuel MayrPublished in: Diabetes (2016)
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.
Keyphrases
- metabolic syndrome
- type diabetes
- insulin resistance
- cell proliferation
- long non coding rna
- long noncoding rna
- high fat diet induced
- mass spectrometry
- fatty acid
- glycemic control
- uric acid
- high fat diet
- cardiovascular disease
- skeletal muscle
- heart failure
- polycystic ovary syndrome
- cardiovascular risk factors
- left ventricular
- study protocol
- randomized controlled trial
- clinical trial
- liquid chromatography
- cross sectional
- high resolution
- transcription factor
- physical activity
- newly diagnosed
- high performance liquid chromatography
- drug delivery
- cancer therapy