Adipose-Derived Circulating miRNAs Regulate Gene Expression in Other Tissues

By Thomas Thomou, M. Mori, Jonathan M. Dreyfuss, M. Konishi, M. Sakaguchi, C. Wolfrum, T. N. Rao, Jonathon N. Winnay, Ruben Garcia-Martin, S. Grinspoon and 2 more. Nature, 2017

1,376 citations recorded by the source corpus.

Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue—brown especially—into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse in vivo can also regulate its 3′ UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/2ab9bb396ec5382aeb039a297683776f34014054

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Ruben Garcia-Martin
2. R. Kahn
3. Jerrold M. Olefsky
4. R. G. Ludwig
5. M. Mori
6. B. Brandao

In Molecular Biology

1. Amanda Birmingham
2. Ruben Garcia-Martin
3. R. Kahn
4. Jerrold M. Olefsky
5. R. G. Ludwig
6. M. Mori
7. B. Brandao
8. P. Calder

In Physiology

1. Jerrold M. Olefsky

Citations in the corpus

• Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. (2017, positive): “Interestingly, whereas Thomou et al. (2017) recently showed that brown adipocytes can secrete Exos containing miR-99b, which suppresses hepatic FGF21 expression, we found no effect of obese or lean ATM-Exos on circulating FGF21 levels in lean or obese recipient mice (Figure S4D).”
• Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “The fact that adipose tissue contributes significantly to the pool of circulating miRNAs is evidenced by the finding that fat-specific knockout of the key miRNA processing enzyme Dicer (ADicerKO) results in significant decreases in about two-thirds of the circulating exosomal miRNAs (Thomou et al., ”