MicroRNA-mediated Regulation of Glucose and Lipid Metabolism

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2021 Mar 27

PMID 33772227

Citations 126

Authors

Pamela Agbu

Richard W Carthew

Affiliations

Soon will be listed here.

Abstract

In animals, systemic control of metabolism is conducted by metabolic tissues and relies on the regulated circulation of a plethora of molecules, such as hormones and lipoprotein complexes. MicroRNAs (miRNAs) are a family of post-transcriptional gene repressors that are present throughout the animal kingdom and have been widely associated with the regulation of gene expression in various contexts, including virtually all aspects of systemic control of metabolism. Here we focus on glucose and lipid metabolism and review current knowledge of the role of miRNAs in their systemic regulation. We survey miRNA-mediated regulation of healthy metabolism as well as the contribution of miRNAs to metabolic dysfunction in disease, particularly diabetes, obesity and liver disease. Although most miRNAs act on the tissue they are produced in, it is now well established that miRNAs can also circulate in bodily fluids, including their intercellular transport by extracellular vesicles, and we discuss the role of such extracellular miRNAs in systemic metabolic control and as potential biomarkers of metabolic status and metabolic disease.

Citing Articles

Aerobic exercise improves inflammation and insulin resistance in skeletal muscle by regulating miR-221-3p via JAK/STAT signaling pathway.

Li N, Zhang L, Guo Q, Shi H, Gan Y, Wang W Front Physiol. 2025; 16:1534911.

PMID: 40070461 PMC: 11893602. DOI: 10.3389/fphys.2025.1534911.

TSH-stimulated hepatocyte exosomes modulate liver-adipose triglyceride accumulation via the TGF-β1/ATGL axis in mice.

Ma S, Wang Y, Fan S, Jiang W, Sun M, Jing M Lipids Health Dis. 2025; 24(1):81.

PMID: 40050912 PMC: 11884018. DOI: 10.1186/s12944-025-02509-6.

Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice.

Lin Y, Pan Y, Jiang T, Chen Y, Shang T, Xu M J Biomed Sci. 2025; 32(1):31.

PMID: 40016734 PMC: 11869713. DOI: 10.1186/s12929-025-01124-y.

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).

Kozlov D, Rodimova S, Kuznetsova D Sovrem Tekhnologii Med. 2025; 15(5):54-79.

PMID: 39967915 PMC: 11832066. DOI: 10.17691/stm2023.15.5.06.

Towards understanding cancer dormancy over strategic hitching up mechanisms to technologies.

Yang S, Seo J, Choi J, Kim S, Kuk Y, Park K Mol Cancer. 2025; 24(1):47.

PMID: 39953555 PMC: 11829473. DOI: 10.1186/s12943-025-02250-9.

References

Carthew R, Sontheimer E . Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009; 136(4):642-55. PMC: 2675692. DOI: 10.1016/j.cell.2009.01.035. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

Filipowicz W, Bhattacharyya S, Sonenberg N . Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet. 2008; 9(2):102-14. DOI: 10.1038/nrg2290. View

Baek D, Villen J, Shin C, Camargo F, Gygi S, Bartel D . The impact of microRNAs on protein output. Nature. 2008; 455(7209):64-71. PMC: 2745094. DOI: 10.1038/nature07242. View

Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N . Widespread changes in protein synthesis induced by microRNAs. Nature. 2008; 455(7209):58-63. DOI: 10.1038/nature07228. View

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J . The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956):415-9. DOI: 10.1038/nature01957. View

Denli A, Tops B, Plasterk R, Ketting R, Hannon G . Processing of primary microRNAs by the Microprocessor complex. Nature. 2004; 432(7014):231-5. DOI: 10.1038/nature03049. View

Gregory R, Yan K, Amuthan G, Chendrimada T, Doratotaj B, Cooch N . The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004; 432(7014):235-40. DOI: 10.1038/nature03120. View

Grishok A, Pasquinelli A, Conte D, Li N, Parrish S, Ha I . Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001; 106(1):23-34. DOI: 10.1016/s0092-8674(01)00431-7. View

10.

Hutvagner G, McLachlan J, Pasquinelli A, Balint E, Tuschl T, Zamore P . A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001; 293(5531):834-8. DOI: 10.1126/science.1062961. View

11.

Ketting R, Fischer S, Bernstein E, Sijen T, Hannon G, Plasterk R . Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001; 15(20):2654-9. PMC: 312808. DOI: 10.1101/gad.927801. View

12.

Meijer H, Smith E, Bushell M . Regulation of miRNA strand selection: follow the leader?. Biochem Soc Trans. 2014; 42(4):1135-40. DOI: 10.1042/BST20140142. View

13.

Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee J, Lotvall J . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9(6):654-9. DOI: 10.1038/ncb1596. View

14.

Chiang H, Schoenfeld L, Ruby J, Auyeung V, Spies N, Baek D . Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev. 2010; 24(10):992-1009. PMC: 2867214. DOI: 10.1101/gad.1884710. View

15.

Jan C, Friedman R, Ruby J, Bartel D . Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs. Nature. 2010; 469(7328):97-101. PMC: 3057491. DOI: 10.1038/nature09616. View

16.

Fromm B, Billipp T, Peck L, Johansen M, Tarver J, King B . A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome. Annu Rev Genet. 2015; 49:213-42. PMC: 4743252. DOI: 10.1146/annurev-genet-120213-092023. View

17.

Kozomara A, Birgaoanu M, Griffiths-Jones S . miRBase: from microRNA sequences to function. Nucleic Acids Res. 2018; 47(D1):D155-D162. PMC: 6323917. DOI: 10.1093/nar/gky1141. View

18.

Fromm B, Domanska D, Hoye E, Ovchinnikov V, Kang W, Aparicio-Puerta E . MirGeneDB 2.0: the metazoan microRNA complement. Nucleic Acids Res. 2019; 48(D1):D1172. PMC: 7145716. DOI: 10.1093/nar/gkz1016. View

19.

Kalvari I, Argasinska J, Quinones-Olvera N, Nawrocki E, Rivas E, Eddy S . Rfam 13.0: shifting to a genome-centric resource for non-coding RNA families. Nucleic Acids Res. 2017; 46(D1):D335-D342. PMC: 5753348. DOI: 10.1093/nar/gkx1038. View

20.

Bartel D . Metazoan MicroRNAs. Cell. 2018; 173(1):20-51. PMC: 6091663. DOI: 10.1016/j.cell.2018.03.006. View