Adipose-derived circulating miRNAs regulate gene expression in other tissues
Open accessAbstract
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.
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Adipose-derived circulating microRNAs are packaged into exosomes and regulate plasma FGF21 levels.
“Although circulating levels of FGF21 are derived from the liver, adipose-derived circulating microRNAs are packaged into exosomes and regulate plasma FGF21 levels (129).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [129]
FGF21 levels can be regulated by adipose-derived exosomes.
“FGF21 levels can also be regulated by adipose-derived exosomes.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [129]
BAT‐produced mir‐99b loaded exosomes contribute to the repression of hepatic FGF21 expression.
“For instance, BAT‐produced mir‐99b loaded exosomes contribute to the repression of hepatic FGF21 expression 171.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [171]
Adipose tissue exosomes carrying circulating miRNAs have far‐reaching effects in other peripheral tissues and can be considered the most recent family of adipokines.
“More precisely, adipose tissue exosomes carrying circulating miRNAs have recently been shown to have far‐reaching effects in other peripheral tissues, and can therefore be considered the most recent family of adipokines 171.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [171]
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References 51 · Cited by 1,539
Research works printed but not linked: 1
- [25]Yao Y Mol Med Rep 2009 2 6 963 21475928
- Authors
- Thomou, T., Mori, M. A., Dreyfuss, J. M., Konishi, M., Sakaguchi, M., Wolfrum, C., Rao, T. N., Winnay, J. N., Garcia-Martin, R., Grinspoon, S. K., Gorden, P., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Boston University (US)
- ETH Zurich (CH)
- Harvard University (US)
- Corresponding author
- Kahn, C. Ronald
- ORCID
- Venue
- Nature
- Published
- 2017-02-23
- Volume
- 542
- Issue
- 7642
- Pages
- 450-455
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5330251
- OpenAlex
- W2588757737
- Cited by
- 1,539
- References
- 51
- Citations by year
- 2026: 117 · 2025: 127 · 2024: 155 · 2023: 176 · 2022: 185 · 2021: 207 · 2020: 199 · 2019: 167 · 2018: 132 · 2017: 71
- FWCI
- 63.70
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-05-11)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031036, R01DK033201, T32DK007260, P30DK036836, P30DK040561, R01DK082659)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- circulating microRNAs, exosomes, adipose tissue, Dicer, lipodystrophy, brown adipose tissue, white adipose tissue, FGF21, glucose tolerance, adipokines, long-range gene regulation, inter-organ communication, microRNA transfer
- MeSH terms
- Adipose Tissue, Animals, Adipose Tissue, Brown, Fibroblast Growth Factors, Gene Expression Regulation, Glucose Tolerance Test, Liver, Male, Models, Biological, Organ Specificity, RNA, Messenger, Transcription, Genetic, Genes, Reporter, Paracrine Communication, 3' Untranslated Regions, MicroRNAs, Ribonuclease III, Mice, Adipose Tissue, White, Adipokines, Exosomes
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