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Extracellular miRNAs as mediators of obesity-associated disease

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 600, Issue 5, Pages 1155-1169

Publisher

WILEY
DOI: 10.1113/JP280910

Keywords

biomarkers; circulating miRNAs; exosomes; obesity; RNA therapy; tissue crosstalk

Funding

  1. NIH [R01DK082659]
  2. Mary K. Iacocca Professorship

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Extracellular miRNAs play crucial roles in regulating gene expression and cellular metabolism, as well as in the pathophysiology of obesity. They are secreted in small vesicles/exosomes or bound to proteins, mainly derived from adipose tissue, and involved in crosstalk between different cells.
Extracellular miRNAs are found in a variety of body fluids and mediate intercellular and interorgan communication, thus regulating gene expression and cellular metabolism. These miRNAs are secreted either in small vesicles/exosomes (sEV) or bound to proteins such as Argonaute and high-density lipoprotein. Both exosomal and protein-bound circulating miRNAs are altered in obesity. Although all tissues can contribute to changes in circulating miRNAs, adipose tissue itself is an important source of these miRNAs, especially those in sEVs. These are derived from both adipocytes and macrophages and participate in crosstalk between these cells, as well as peripheral tissues, including liver, skeletal muscle and pancreas, whose function may be impaired in obesity. Changes in levels of circulating miRNAs have also been linked to the beneficial effects induced by weight loss interventions, including diet, exercise and bariatric surgery, further indicating a role for these miRNAs as mediators of disease pathogenesis. Here, we review the role of circulating miRNAs in the pathophysiology of obesity and explore their potential use as biomarkers and in therapy of obesity-associated metabolic syndrome.

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