PT  - JOURNAL ARTICLE
AU  - Jasmine Gajeton
AU  - Irene Krukovets
AU  - Revanth Yendamuri
AU  - Dmitriy Verbovetskiy
AU  - Amit Vasanji
AU  - Lidiya Sul
AU  - Olga Stenina-Adognravi
TI  - miR-467 regulates inflammation and blood insulin and glucose
AID  - 10.1101/666545
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 666545
4099  - http://biorxiv.org/content/early/2020/12/14/666545.short
4100  - http://biorxiv.org/content/early/2020/12/14/666545.full
AB  - Obesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycemia, in regulating inflammation and blood glucose handling.We previously demonstrated that miR-467a-5p is induced by hyperglycemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57/BL6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1−/− (and other unknown transcripts) are targeted by miR-467 to regulate inflammation.miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.Competing Interest StatementThe authors have declared no competing interest.