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The role of miR‐146a‐5p on insulin signaling and inflammation in adipose tissue of longliving Ames dwarf mice.
Author(s) -
De Carvalho Nunes Allancer Divino,
Yu Lin,
Lahde Collin,
Noureddine Sarah,
Saccon Tatiana,
Schneider Augusto,
Masternak Michal
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09496
Subject(s) - adipose tissue , inflammation , adiponectin , endocrinology , medicine , microrna , biology , in vivo , senescence , downregulation and upregulation , gene expression , insulin , insulin resistance , gene , genetics
MicroRNAs have been shown to be potent regulators of various biological processes. Multiple miRNAs are regulated during aging in several tissues from mice. Previous studies have indicated the MicroRNA 146a‐5p (miR‐146a) is increased during aging in the circulation, in a wide variety of tissues and different models of replicative aging. Importantly, this miRNA is also associated with cellular senescence, metabolic syndrome and inflammation. Thus, the aim of this study was to determine the mechanistic role of miR‐146a in insulin sensitivity and inflammation in visceral fat tissue in vivo. For this we used Long‐living Ames dwarf (df/df) and normal (N) female mice were subjected to five intraperitoneal injections of a miR‐146a mimetic (miR‐146a‐m) with two day intervals between each injection. Before the treatment, mice were randomly divide into five experimental groups: normal mice control, normal mice miR‐146a‐m 4 mg/kg, df/df control, df/df miR‐146a‐m 4mg/kg and df/df miR‐146a‐m 8 mg/kg. Overall, RT‐PCR analysis indicated that in vivo treatment with miR‐146‐m increased the expression level of miR‐146a in visceral fat tissue in both N and df/df mice. Importantly, in df/df the treatment with miR‐146a‐m 8 mg/kg significantly increased P16 gene expression, a known senescence marker, and reduced adiponectin, IRS2 and AKT1 gene expression. Moreover, the analysis of PI3K, IRS1, PPARƴ and PPARα gene expression in visceral fat showed a trend towards downregulation in response to treatment with miR‐146a‐m at 8 mg/kg. In summary, this study showed that miR‐146a regulated the expression genes related to insulin sensitivity in visceral fat tissue in long‐living df/df mice as compared to normal mice. Additionally, our data suggest that miR‐146a might suppress insulin sensitivity and stimulate inflammation through suppression of adiponectin levels. Support or Funding Information This research study is supported by National Institutes of Health (NIH) (R15AG059190, R03AG059846 and R56AG061414)