MicroRNAs (miRNAs) produced in adipose tissue cells and released into the circulation encapsulated in small extracellular vesicles (exosomes) can affect gene expression in distant organs, new research shows. These findings might indicate that exosomal miRNAs represent a previously undescribed form of adipokine.
To investigate the role of adipocyte-derived miRNAs, Thomou et al. generated mice lacking Dicer (the enzyme that processes miRNAs) in adipose tissue using a Cre–lox gene recombination strategy. The resulting ADicerKO mice had an overall decrease in circulating levels of exosomal miRNAs compared with wild-type mice; levels of 419 miRNAs were significantly decreased, and those of three miRNAs were significantly increased. Similar results were found when miRNA levels were analysed in serum from patients with congenital generalized lipodystrophy or HIV-associated lipodystrophy (who have low levels of Dicer in adipose tissue).
Transplanting fat from normal mice into ADicerKO mice restored circulating levels of exosomal miRNAs, an effect that was particularly marked when brown adipose tissue was transplanted. This finding confirms that adipose tissue is the source of these exosomal miRNAs.
Interestingly, ADicerKO mice had a threefold increase in circulating levels of the metabolic factor FGF21, compared with wild-type mice. Levels of Fgf21 mRNA were also increased in liver, muscle, fat and pancreas. On transplantation of brown adipose tissue from control mice, levels of Fgf21 mRNA in the livers of ADicerKO mice decreased by ~50%, which was accompanied by a reduction in circulating levels of FGF21. Thus, transplantation of brown adipose tissue seems to provide a factor that regulates FGF21 expression. Further analyses implicated miR-99b — which is present in exosomes derived from brown adipose tissue — in the regulation of FGF21 expression in the liver.
these miRNAs could be involved in regulating whole-body metabolism
“Our data show that adipose tissue is an important source of circulating exosomal miRNAs in both mice and humans,” write the authors. They also conclude that these miRNAs could be involved in regulating whole-body metabolism and mRNA translation in other tissues.
This article is modified from the original in Nat. Rev. Endocrinol. (http://dx.doi.org/10.1038/nrendo.2017.22)
Thomou, T. et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature http://dx.doi.org/10.1038/nature21365 (2017)
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Greenhill, C. Exosomal microRNAs as novel adipokines. Nat Rev Genet 18, 212 (2017). https://doi.org/10.1038/nrg.2017.14
Current Diabetes Reports (2018)