Open AccessmiR‐467 regulates inflammation and blood insulin and glucose
Author(s) -
Gajeton Jasmine,
Krukovets Irene,
Yendamuri Revanth,
Verbovetskiy Dmitriy,
Vasanji Amit,
Sul Lidiya,
SteninaAdognravi Olga
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16224
Subject(s) - inflammation , medicine , endocrinology , insulin resistance , adipose tissue , insulin , carbohydrate metabolism , glucose uptake , biology
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 hyperglycaemia, in regulating inflammation and blood glucose handling. We previously demonstrated that miR‐467a‐5p is induced by hyperglycaemia 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 C57BL/6 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 ng/mL 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.