American Diabetes Association
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Changes in Circulating miR-375-3p and Improvements in Visceral and Hepatic Fat Contents in Response to Lifestyle Interventions: The CENTRAL Trial

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posted on 2022-06-03, 11:49 authored by Yoriko Heianza, Knut Krohn, Anat Yaskolka Meir, Xuan Wang, Stefanie Ziesche, Uta Ceglarek, Matthias Blüher, Maria Keller, Peter Kovacs, Iris Shai, Lu Qi


Objective: To investigate whether changes in circulating levels of pancreatic islet-related microRNA-375 (miR-375) were related to improved visceral and intrahepatic fat accumulation. 

Research Design and Methods: This study included adults with abdominal obesity from an 18-month weight-loss lifestyle intervention trial. Circulating miR-375-3p was measured at baseline and 18 months. The magnetic-resonance-imaging (MRI) was performed (n=139) to assess 18-month changes in abdominal and intrahepatic fat depots.

Results: Circulating miR-375-3p was related to fasting insulin and insulin resistance in participants with pre-diabetes. After the interventions, there was a significant increase of miR-375-3p (p <0.001). Greater increase in miR-375-3p was associated with larger reductions of visceral (p=0.024) and deep subcutaneous adipose tissues (p <0.001), and intrahepatic fat content (p=0.012).

Conclusions: Increases in circulating miR-375-3p were associated with visceral and intrahepatic fat reduction. Changes in circulating pancreatic islet-related miR-375-3p may be linked to improved diabetogenic fat depots during weight-loss lifestyle interventions. 


The study is supported by National Institutes of Health (NIH) grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK115679), the Boston Obesity Nutrition Research Center (DK46200), and United States-Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research and Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science. YH is a recipient of the 2019 American Heart Association postdoctoral fellowship award (19POST34380035). The CENTRAL study has been supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation –209933838 – SFB 1052; B01, B03, B11, Z04) and Deutsches Zentrum für Diabetesforschung, the Israel Science Foundation (ISF), Israel Ministry of Science and Technology (grant # 3-13604), and the Dr. Robert C. and Veronica Atkins Research Foundation. The sponsors had no role in the design or conduct of the study.


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