Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Runtsch, MC; Nelson, MC; Lee, SH; Voth, W; Alexander, M; Hu, R; Wallace, J; Petersen, C; Panic, V; Villanueva, CJ; Evason, KJ; Bauer, KM; Mosbruger, T; Boudina, S; Bronner, M; Round, JL; Drummond, MJ; O'Connell, RM.
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
PLoS Genet. 2019; 15(2):e1007970
Doi: 10.1371/journal.pgen.1007970
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- Runtsch Marah
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Blood Glucose - metabolism
- Diet, High-Fat - adverse effects
- Disease Models, Animal - administration & dosage
- Female - administration & dosage
- Gene Expression - administration & dosage
- Humans - administration & dosage
- Hyperglycemia - genetics, metabolism, prevention & control
- Inflammation - genetics, metabolism, prevention & control
- Insulin - blood
- Intra-Abdominal Fat - metabolism, pathology
- Macrophages - metabolism
- Male - administration & dosage
- Metabolic Diseases - genetics, metabolism, prevention & control
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Mice, Knockout - administration & dosage
- MicroRNAs - antagonists & inhibitors, genetics, metabolism
- NF-kappa B - metabolism
- Obesity - genetics, metabolism, prevention & control
- Proto-Oncogene Proteins c-akt - genetics
- Sirolimus - pharmacology
- TOR Serine-Threonine Kinases - antagonists & inhibitors, genetics
- Weight Gain - drug effects, genetics