PLoS genetics, 2019-02, Vol.15 (2), p.e1007970-e1007970
2019
Details
- Autor(en) / Beteiligte
- Titel
- Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease
- Ist Teil von
- PLoS genetics, 2019-02, Vol.15 (2), p.e1007970-e1007970
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7404, 1553-7390eISSN: 1553-7404DOI: 10.1371/journal.pgen.1007970Titel-ID: cdi_plos_journals_2251042197
- Format
- –
- Schlagworte
- Adipose tissue, Animals, Anti-inflammatory agents, Anti-inflammatory diet, Anti-inflammatory drugs, Biochemistry, Biology and Life Sciences, Blood glucose, Blood Glucose - metabolism, Body composition, Body fat, Body weight gain, Cancer, Comparative analysis, Diabetes, Diabetes mellitus, Diet, Diet, High-Fat - adverse effects, Disease, Disease Models, Animal, Female, Gene Expression, Genes, Genetic aspects, Glucose, Glycolysis, High fat diet, Homeostasis, Humans, Hyperglycemia - genetics, Hyperglycemia - metabolism, Hyperglycemia - prevention & control, Inflammation, Inflammation - genetics, Inflammation - metabolism, Inflammation - prevention & control, Insulin - blood, Insulin resistance, Intra-Abdominal Fat - metabolism, Intra-Abdominal Fat - pathology, Macrophages, Macrophages - metabolism, Male, Medical research, Medicine and Health Sciences, Metabolic diseases, Metabolic Diseases - genetics, Metabolic Diseases - metabolism, Metabolic Diseases - prevention & control, Metabolic disorders, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNA, MicroRNAs, MicroRNAs - antagonists & inhibitors, MicroRNAs - genetics, MicroRNAs - metabolism, miRNA, NF-kappa B - metabolism, NF-κB protein, Novels, Obesity, Obesity - genetics, Obesity - metabolism, Obesity - prevention & control, Pathology, Phenotypes, Physiological aspects, Prevention, Proto-Oncogene Proteins c-akt - genetics, Rapamycin, RNA, Salt, Sirolimus - pharmacology, Supervision, TOR protein, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - genetics, TRAF6 protein, Transcription activation, Weight Gain - drug effects, Weight Gain - genetics