SpringerLink
Log in

MiR-499/PRDM16 axis modulates the adipogenic differentiation of mouse skeletal muscle satellite cells

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Obesity is associated with increased risks of diverse diseases; brown adipose tissue (BAT) can increase energy expenditure and protect against obesity by increasing the decomposition of white adipose tissue (WAT) to enhance the non-coupled oxidative phosphorylation of fatty acid in adipocytes and contributes to weight loss. However, BAT is abundant in only small rodents and newborn humans, but not in adults. PRDM16 is a key factor that induces the differentiation of skeletal muscle precursors to brown adipocytes and simultaneously inhibits myogenic differentiation. In the present study, we set insulin-induced skeletal muscle satellite cells (SMSCs) adipogenic differentiation model, as confirmed by the contents of adipogenic markers PRDM16, UCP1 and PGC1α and myogenic markers MyoD1 and MyoG. We selected miR-499 as candidate miRNA, which might regulate PRDM16 to affect SMSCs adipogenic differentiation. Possibly through directly binding to PRDM16 3′-UTR, miR-499 negatively regulated PRDM16 expression and hindered SMSCs adipogenic differentiation by reducing adipogenic markers PRDM16, UCP1 and PGC1α and increasing myogenic markers MyoD1 and MyoG. PRDM16 overexpression could partially reverse the effect of miR-499 on the above markers and SMSCs adipogenic differentiation. Taken together, miR-499/PRDM16 axis can affect the balance between SMSC myogenic and adipogenic differentiation, targeting miR-499 to rescue PRDM16 expression, thus promoting SMSCs adipogenic differentiation may be a promising strategy for obesity treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Wang H, Peng DQ. New insights into the mechanism of low high-density lipoprotein cholesterol in obesity. Lipids Health Dis. 2011;10:176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Wu CL, Zhao SP, Yu BL. Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non-alcoholic fatty liver disease. Biol Rev Camb Philos Soc. 2015;90:367–76.

    Article  PubMed  Google Scholar 

  3. Yu BL, Zhao SP, Hu JR. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity. Obes Rev. 2010;11:560–7.

    Article  PubMed  CAS  Google Scholar 

  4. Liu X, Cervantes C, Liu F. Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity. Protein Cell. 2017;8:446–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377:557–67.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Doak CM, Wijnhoven TM, Schokker DF, Visscher TL, Seidell JC. Age standardization in map** adult overweight and obesity trends in the WHO European Region. Obes Rev. 2012;13:174–91.

    Article  PubMed  CAS  Google Scholar 

  7. Sun X, Li P, Yang X, Li W, Qiu X, Zhu S. From genetics and epigenetics to the future of precision treatment for obesity. Gastroenterol Rep (Oxf). 2017;5:266–70.

    Article  Google Scholar 

  8. Giralt M, Villarroya F. White, brown, beige/brite: different adipose cells for different functions? Endocrinology. 2013;154:2992–3000.

    Article  PubMed  CAS  Google Scholar 

  9. Cinti S. The adipose organ. Prostaglandins Leukot Essent Fatty Acids. 2005;73:9–15.

    Article  PubMed  CAS  Google Scholar 

  10. Cypess AM, Kahn CR. The role and importance of brown adipose tissue in energy homeostasis. Curr Opin Pediatr. 2010;22:478–84.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Seale P, Lazar MA. Brown fat in humans: turning up the heat on obesity. Diabetes. 2009;58:1482–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Tseng YH, Cypess AM, Kahn CR. Cellular bioenergetics as a target for obesity therapy. Nat Rev Drug Discov. 2010;9:465–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Stephens M, Ludgate M, Rees DA. Brown fat and obesity: the next big thing? Clin Endocrinol (Oxf). 2011;74:661–70.

    Article  CAS  Google Scholar 

  15. Almind K, Manieri M, Sivitz WI, Cinti S, Kahn CR. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice. Proc Natl Acad Sci USA. 2007;104:2366–71.

    Article  PubMed  CAS  Google Scholar 

  16. Lepper C, Fan CM. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis. 2010;48:424–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454:961–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007;6:38–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Farmer SR. Molecular determinants of brown adipocyte formation and function. Genes Dev. 2008;22:1269–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Chinnadurai G. Transcriptional regulation by C-terminal binding proteins. Int J Biochem Cell Biol. 2007;39:1593–607.

    Article  PubMed  CAS  Google Scholar 

  21. Kajimura S, Seale P, Tomaru T, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev. 2008;22:1397–409.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Yin H, Pasut A, Soleimani VD, et al. MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16. Cell Metab. 2013;17:210–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Danoviz ME, Yablonka-Reuveni Z. Skeletal muscle satellite cells: background and methods for isolation and analysis in a primary culture system. Methods Mol Biol. 2012;798:21–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Gharaibeh B, Lu A, Tebbets J, et al. Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique. Nat Protoc. 2008;3:1501–9.

    Article  PubMed  CAS  Google Scholar 

  25. Harding RL, Clark DL, Halevy O, Coy CS, Yahav S, Velleman SG. The effect of temperature on apoptosis and adipogenesis on skeletal muscle satellite cells derived from different muscle types. Physiol Rep. 2015. https://doi.org/10.14814/phy2.12539.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Scime A, Grenier G, Huh MS, et al. Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1alpha. Cell Metab. 2005;2:283–95.

    Article  PubMed  CAS  Google Scholar 

  27. Tang R, Ma F, Li W, Ouyang S, Liu Z, Wu J. miR-206-3p Inhibits 3T3-L1 Cell Adipogenesis via the c-Met/PI3K/Akt Pathway. Int J Mol Sci. 2017;18(7):1510. https://doi.org/10.3390/ijms18071510.

    Article  PubMed Central  CAS  Google Scholar 

  28. Saccone V, Consalvi S, Giordani L, et al. HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles. Genes Dev. 2014;28:841–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Jang YJ, Jung CH, Ahn J, Gwon SY, Ha TY. Shikonin inhibits adipogenic differentiation via regulation of mir-34a-FKBP1B. Biochem Biophys Res Commun. 2015;467:941–7.

    Article  PubMed  CAS  Google Scholar 

  30. Sun YM, Qin J, Liu SG, et al. PDGFRα Regulated by miR-34a and FoxO1 Promotes Adipogenesis in Porcine Intramuscular Preadipocytes through Erk Signaling Pathway. Int J Mol Sci. 2017;18(11):2424. https://doi.org/10.3390/ijms18112424.

    Article  PubMed Central  CAS  Google Scholar 

  31. Bork S, Horn P, Castoldi M, Hellwig I, Ho AD, Wagner W. Adipogenic differentiation of human mesenchymal stromal cells is down-regulated by microRNA-369-5p and up-regulated by microRNA-371. J Cell Physiol. 2011;226:2226–34.

    Article  PubMed  CAS  Google Scholar 

  32. Walden TB, Petrovic N, Nedergaard J. PPARalpha does not suppress muscle-associated gene expression in brown adipocytes but does influence expression of factors that fingerprint the brown adipocyte. Biochem Biophys Res Commun. 2010;397:146–51.

    Article  PubMed  CAS  Google Scholar 

  33. Fu T, Seok S, Choi S, et al. MicroRNA 34a inhibits beige and brown fat formation in obesity in part by suppressing adipocyte fibroblast growth factor 21 signaling and SIRT1 function. Mol Cell Biol. 2014;34:4130–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Nesan D, Tavallaee G, Koh D, Bashiri A, Abdin R, Ng DS. Lecithin:Cholesterol Acyltransferase (LCAT) deficiency promotes differentiation of satellite cells to brown adipocytes in a cholesterol-dependent manner. J Biol Chem. 2015;290:30514–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Tiraby C, Tavernier G, Lefort C, et al. Acquirement of brown fat cell features by human white adipocytes. J Biol Chem. 2003;278:33370–6.

    Article  PubMed  CAS  Google Scholar 

  36. Megeney LA, Kablar B, Garrett K, Anderson JE, Rudnicki MA. MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes Dev. 1996;10:1173–83.

    Article  PubMed  CAS  Google Scholar 

  37. Weintraub H, Davis R, Tapscott S, et al. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991;251:761–6.

    Article  PubMed  CAS  Google Scholar 

  38. Brunetti A, Goldfine ID. Role of myogenin in myoblast differentiation and its regulation by fibroblast growth factor. J Biol Chem. 1990;265:5960–3.

    PubMed  CAS  Google Scholar 

  39. Yutzey KE, Rhodes SJ, Konieczny SF. Differential trans activation associated with the muscle regulatory factors MyoD1, myogenin, and MRF4. Mol Cell Biol. 1990;10:3934–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. 2007;131:242–56.

    Article  PubMed  CAS  Google Scholar 

  41. Hansen JB, Kristiansen K. Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem J. 2006;398:153–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Rosen ED, Spiegelman BM. Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 2000;16:145–71.

    Article  PubMed  CAS  Google Scholar 

  43. Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation. 2001;68:245–53.

    Article  PubMed  CAS  Google Scholar 

  44. Shefer G, Wleklinski-Lee M, Yablonka-Reuveni Z. Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway. J Cell Sci. 2004;117:5393–404.

    Article  PubMed  CAS  Google Scholar 

  45. Stranger BE, Stahl EA, Raj T. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 2011;187:367–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Ebert MS, Sharp PA. Roles for microRNAs in conferring robustness to biological processes. Cell. 2012;149:515–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Dumortier O, Hinault C, Van Obberghen E. MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab. 2013;18:312–24.

    Article  PubMed  CAS  Google Scholar 

  48. Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol. 2003;13:790–5.

    Article  PubMed  CAS  Google Scholar 

  49. Jordan SD, Kruger M, Willmes DM, et al. Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol. 2011;13:434–46.

    Article  PubMed  CAS  Google Scholar 

  50. Wang XY, Chen XL, Huang ZQ, Chen DW, Yu B, He J, Luo JQ, Luo YH, Chen H, Zheng P, Yu J. MicroRNA-499-5p regulates porcine myofiber specification by controlling Sox6 expression. Animal. 2017;11(12):2268–74.

    Article  PubMed  CAS  Google Scholar 

  51. Drummond MJ, Glynn EL, Fry CS, Dhanani S, Volpi E, Rasmussen BB. Essential amino acids increase microRNA-499, -208b, and -23a and downregulate myostatin and myocyte enhancer factor 2C mRNA expression in human skeletal muscle. J Nutr. 2009;139:2279–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Becerril S, Gomez-Ambrosi J, Martin M, et al. Role of PRDM16 in the activation of brown fat programming. Relevance to the development of obesity. Histol Histopathol. 2013;28:1411–25.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Hunan National Natural Science Fund (2015jj2155).

Author information

Authors and Affiliations

  1. Department of General Surgery, Third **angya Hospital, Central South University, 138 Tongzipo Street, Changsha, 410013, Hunan, People’s Republic of China

    Juan Jiang, PengZhou Li, Hao Ling, ZhouZhou Xu, Bo Yi & Shaihong Zhu

Authors
  1. Juan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. PengZhou Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. ZhouZhou Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shaihong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bo Yi or Shaihong Zhu.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, J., Li, P., Ling, H. et al. MiR-499/PRDM16 axis modulates the adipogenic differentiation of mouse skeletal muscle satellite cells. Human Cell 31, 282–291 (2018). https://doi.org/10.1007/s13577-018-0210-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-018-0210-5

Keywords

Search

Navigation