Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.

Autor: Runtsch MC; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Nelson MC; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Lee SH; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Voth W; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Alexander M; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Hu R; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Wallace J; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Petersen C; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Panic V; Department of Biochemistry, University of Utah, Salt Lake City, Utah, United States of America., Villanueva CJ; Department of Biochemistry, University of Utah, Salt Lake City, Utah, United States of America., Evason KJ; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Bauer KM; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Mosbruger T; Bioinformatics, Huntsman Cancer Institute and University of Utah, Salt Lake City, Utah, United States of America., Boudina S; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah, United States of America., Bronner M; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Round JL; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America., Drummond MJ; Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah, United States of America., O'Connell RM; Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2019 Feb 15; Vol. 15 (2), pp. e1007970. Date of Electronic Publication: 2019 Feb 15 (Print Publication: 2019).
DOI: 10.1371/journal.pgen.1007970
Abstrakt: Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-κB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje