Obesity is a complex condition that is characterized by excessive fat accumulation, which can lead to the development of metabolic disorders, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease and cardiovascular diseases. Evidence is accumulating that circulating microRNAs (miRNAs) act as a new class of endocrine factor. These miRNAs are released by many types of tissue, including adipose tissues. miRNAs might serve as endocrine and paracrine messengers that facilitate communication between donor cells and tissues with receptor cells or target tissues, thereby potentially having important roles in metabolic organ crosstalk. Moreover, many miRNAs are closely associated with the differentiation of adipocytes and are dysregulated in obesity. As such, circulating miRNAs are attractive potential biomarkers and hold promise for the development of miRNA-based therapeutics (such as miRNA mimetics, anti-miRNA oligonucleotides and exosomes loaded with miRNA) for obesity and related disorders. Here we review the latest research progress on the roles of circulating miRNAs in metabolic organ crosstalk. In addition, we discuss the clinical potential of circulating miRNAs as feasible biomarkers for the assessment of future risk of metabolic disorders and as therapeutic targets in obesity and related diseases.
Circulating microRNAs (miRNAs) can be secreted from different tissues, including adipose tissue, and affect the metabolic profiles of distant organs, thereby facilitating metabolic organ crosstalk.
In individuals with obesity and/or metabolic disease, the profile of circulating miRNAs is different from that seen in lean individuals.
Adipocyte-specific miRNA-deficient mouse models demonstrate the importance of circulating adipocyte-derived miRNAs for metabolic health.
Adipose tissue-derived and/or obesity-associated circulating miRNAs have potential as biomarkers for the prevention and management of obesity and metabolic diseases.
Evidence is accumulating that obesity-associated and/or adipose tissue-derived circulating miRNAs are promising new therapeutic targets for the treatment of obesity and related diseases.
The development of novel therapeutics, such as miRNA mimetics, anti-miRNA oligonucleotides and exosomes loaded with miRNAs, might allow the clinical application of miRNA-based therapeutics for obesity and metabolic disease.
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The authors acknowledge the support of the National Natural Science Foundation of China (grant nos 81200642, 81670773 and 81770866) and the Jiangsu Provincial Key Research and Development Programme (grant nos BE2016619 and BE2018614).
The authors declare no competing interests.
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Homogenous extracellular vesicles (40–100 nm) that originate from the endocytic recycling pathway, with specific markers such as CD9, CD63, ALIX, flotillin 1 and TSG101.
Heterogeneous extracellular vesicles (50–1,000 nm) that are produced directly through the outward budding and fission of membrane vesicles from the plasma membrane with no definite markers.
A genetic or acquired disorder characterized by a lack of adipose tissue.
- Nonalcoholic steatohepatitis
(NASH). A severe form of nonalcoholic fatty liver disease characterized by abnormal accumulation of fat and liver inflammation that is not caused by alcohol abuse, which might lead to complications such as cirrhosis, liver cancer and liver failure.
- Polypyrimidine tract-binding protein 1
(PTBP1). A protein that can stabilize insulin mRNA and facilitate insulin translation.
- Macrophage foam cell
A type of macrophage containing cholesterol with a foamy appearance that has a key role in the development of atherosclerosis.
- Droplet digital PCR
A technique used to quantify the absolute copies of nucleic acids directly.
- Small interfering RNAs
A class of exogenous double-stranded RNA molecules, 20–25 base pairs in length, similar to microRNAs, and used widely as a gene silencing tool.
A type of fibrous scar tissue.
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Ji, C., Guo, X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol 15, 731–743 (2019) doi:10.1038/s41574-019-0260-0