Back to Search
Start Over
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
- Source :
-
PLoS genetics [PLoS Genet] 2019 Feb 15; Vol. 15 (2), pp. e1007970. Date of Electronic Publication: 2019 Feb 15 (Print Publication: 2019). - Publication Year :
- 2019
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Blood Glucose metabolism
Diet, High-Fat adverse effects
Disease Models, Animal
Female
Gene Expression
Humans
Hyperglycemia genetics
Hyperglycemia metabolism
Hyperglycemia prevention & control
Inflammation genetics
Inflammation metabolism
Insulin blood
Intra-Abdominal Fat metabolism
Intra-Abdominal Fat pathology
Macrophages metabolism
Male
Metabolic Diseases genetics
Metabolic Diseases metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs antagonists & inhibitors
NF-kappa B metabolism
Obesity genetics
Obesity metabolism
Obesity prevention & control
Proto-Oncogene Proteins c-akt genetics
Sirolimus pharmacology
TOR Serine-Threonine Kinases antagonists & inhibitors
TOR Serine-Threonine Kinases genetics
Weight Gain drug effects
Weight Gain genetics
Inflammation prevention & control
Metabolic Diseases prevention & control
MicroRNAs genetics
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 30768595
- Full Text :
- https://doi.org/10.1371/journal.pgen.1007970