Astragalus polysaccharide regulates brown adipocytes differentiation by miR-6911 targeting Prdm16.


Journal

Lipids
ISSN: 1558-9307
Titre abrégé: Lipids
Pays: United States
ID NLM: 0060450

Informations de publication

Date de publication:
01 2022
Historique:
revised: 15 10 2021
received: 25 08 2021
accepted: 21 10 2021
pubmed: 6 11 2021
medline: 28 1 2022
entrez: 5 11 2021
Statut: ppublish

Résumé

Brown adipose tissue (BAT) is a specialized tissue in mammals related to thermogenesis. The Astragalus polysaccharide (APS) is the major natural active component of Astragalus membranaceus, which has been recognized as one of the most popular herbal medicines worldwide. The role and possible mechanisms of APS on brown adipocytes differentiation is not well defined. Here, we explored the effect of APS on the differentiation of brown adipocytes in C3H10T 1/2 cells. The results showed that APS promoted the differentiation of brown adipocytes and improved insulin sensitivity along with significant increases in the expression of brown adipogenic marker proteins (C/EBPα, C/EBPβ, and PPARγ), thermogenesis marker proteins (UCP1, PRDM16, and PGC-1α), and insulin sensitivity marker protein (GLUT4). Meanwhile, the results showed that the amount of the phosphorylation of insulin receptor substrate 1 (p-IRS1) and phospho-AKT (p-AKT) which are critical factors in the insulin signaling pathway was increased without changing the total amount of IRS and AKT. Furthermore, the results of RNA-seq showed that APS altered the expression profiles of various miRNAs, and among which the expression of miR-6911 as a universal regulatory factor was significantly decreased. Importantly, we found that miR-6911 regulated the differentiation of brown adipocytes by targeting PR domain-containing 16 (Prdm16). In addition, after transfection of miR-6911 mimics, compared with the control and inhibitor group, PRDM16 protein expression significantly decreased, which was accompanied by the decrease of PPARγ, UCP1, and PGC-1α. Collectively, our results indicated that APS regulated brown adipocytes differentiation in C3H10T 1/2 cells via miRNA-6911 targeting Prdm16.

Identifiants

pubmed: 34738642
doi: 10.1002/lipd.12328
doi:

Substances chimiques

DNA-Binding Proteins 0
MicroRNAs 0
Polysaccharides 0
Prdm16 protein, mouse 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

45-55

Informations de copyright

© 2021 AOCS.

Références

Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409(6821):729-33. https://doi.org/10.1038/35055575
Agyemang K, Han L, Liu E, Zhang Y, Wang T, Gao X. Recent advances in Astragalus membranaceus anti-diabetic research: Pharmacological effects of its phytochemical constituents. Evid Based Complement Alternat Med. 2013;2013:654643. https://doi.org/10.1155/2013/654643
Alcala M, Calderon-Dominguez M, Serra D, Herrero L, Viana M. Mechanisms of impaired brown adipose tissue recruitment in obesity. Front Physiol. 2019;10:94. https://doi.org/10.3389/fphys.2019.00094
Arias N, Aguirre L, Fernández-Quintela A, González M, Lasa A, Miranda J, et al. MicroRNAs involved in the browning process of adipocytes. J Physiol Biochem. 2016;72(3):509-21. https://doi.org/10.1007/s13105-015-0459-z
Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev. 2004;84(1):277-359. https://doi.org/10.1152/physrev.00015.2003
Chen Y, Pan R, Pfeifer A. Regulation of brown and beige fat by microRNAs. Pharmacol Ther. 2017;170:1-7. https://doi.org/10.1016/j.pharmthera.2016.10.004
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509-17. https://doi.org/10.1056/NEJMoa0810780
Fernandez-Verdejo R, Marlatt KL, Ravussin E, Galgani JE. Contribution of brown adipose tissue to human energy metabolism. Mol Aspects Med. 2019;68:82-9. https://doi.org/10.1016/j.mam.2019.07.003
Gallagher EJ, LeRoith D. Obesity and diabetes: The increased risk of cancer and cancer-related mortality. Physiol Rev. 2015;95(3):727-48. https://doi.org/10.1152/physrev.00030.2014
Gavalda-Navarro A, Villarroya J, Cereijo R, Giralt M, Villarroya F. The endocrine role of brown adipose tissue: An update on actors and actions. Rev Endocr Metab Disord. 2021. https://doi.org/10.1007/s11154-021-09640-6
Goody D, Pfeifer A. MicroRNAs in brown and beige fat. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(1):29-36. https://doi.org/10.1016/j.bbalip.2018.05.003
Goto T. A review of the studies on food-derived factors which regulate energy metabolism via the modulation of lipid-sensing nuclear receptors. Biosci Biotechnol Biochem. 2019;83(4):579-88. https://doi.org/10.1080/09168451.2018.1559025
Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression. J Transl Med. 2016;14(1):143. https://doi.org/10.1186/s12967-016-0893-x
Harms M, Seale P. Brown and beige fat: Development, function and therapeutic potential. Nat Med. 2013;19(10):1252-63. https://doi.org/10.1038/nm.3361
Horie T, Nakao T, Miyasaka Y, Nishino T, Matsumura S, Nakazeki F, et al. microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity. Nat Commun. 2021;12(1):843. https://doi.org/10.1038/s41467-021-21107-5
Icli B, Feinberg MW. MicroRNAs in dysfunctional adipose tissue: Cardiovascular implications. Cardiovas Res. 2017;113(9):1024-34. https://doi.org/10.1093/cvr/cvx098
Jakab J, Miškić B, Mikšić Š, Juranić B, Ćosić V, Schwarz D, et al. Adipogenesis as a potential anti-obesity target: A review of pharmacological treatment and natural products. Diabetes Metab Syndr Obes. 2021;14:67-83. https://doi.org/10.2147/DMSO.S281186
Jin M, Zhao K, Huang Q, Shang P. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol. 2014;64:257-66. https://doi.org/10.1016/j.ijbiomac.2013.12.002
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, et al. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature. 2009;460(7259):1154-8. https://doi.org/10.1038/nature08262
Kong X, Yu J, Bi J, Qi H, di W, Wu L, et al. Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes. 2015;64(2):393-404. https://doi.org/10.2337/db14-0395
Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, et al. Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci U S A. 2017;114(32):8649-54. https://doi.org/10.1073/pnas.1705287114
Leto D, Saltiel AR. Regulation of glucose transport by insulin: Traffic control of GLUT4. Nat Rev Mol Cell Bio. 2012;13(6):383-96. https://doi.org/10.1038/nrm3351
Li X, Qu L, Dong Y, Han L, Liu E, Fang S, et al. A review of recent research progress on the Astragalus genus. Molecules (Basel, Switzerland). 2014;19(11):18850-80. https://doi.org/10.3390/molecules191118850
Mao XQ, Yu F, Wang N, Wu Y, Zou F, Wu K, et al. Hypoglycemic effect of polysaccharide enriched extract of Astragalus membranaceus in diet induced insulin resistant C57BL/6J mice and its potential mechanism. Phytomedicine. 2009;16(5):416-25. https://doi.org/10.1016/j.phymed.2008.12.011
Misiewicz-Krzeminska I, Krzeminski P, Corchete LA, Quwaider D, Rojas EA, Herrero AB, et al. Factors regulating microRNA expression and function in multiple myeloma. Noncoding RNA. 2019;5(1):9. https://doi.org/10.3390/ncrna5010009
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766-81. https://doi.org/10.1016/S0140-6736(14)60460-8
Nie T, Zhao S, Mao L, Yang Y, Sun W, Lin X, et al. The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARgamma activity. Br J Pharmacol. 2018;175(9):1439-50. https://doi.org/10.1111/bph.14139
Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 2012;15(3):395-404. https://doi.org/10.1016/j.cmet.2012.01.019
Schreiber I, Dörpholz G, Ott CE, Kragesteen B, Schanze N, Lee CT, et al. BMPs as new insulin sensitizers: Enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation. Sci Rep. 2017;7(1):17192. https://doi.org/10.1038/s41598-017-17595-5
Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454(7207):961-7. https://doi.org/10.1038/nature07182
Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007;6(1):38-54. https://doi.org/10.1016/j.cmet.2007.06.001
Stanford KI, Middelbeek RJW, Townsend KL, An D, Nygaard EB, Hitchcox KM, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013;123(1):215-23. https://doi.org/10.1172/JCI62308
Symonds ME. Brown adipose tissue growth and development. Scientifica (Cairo). 2013;2013:305763. https://doi.org/10.1155/2013/305763
Trajkovski M, Lodish H. MicroRNA networks regulate development of brown adipocytes. Trends Endocrinol Metab. 2013;24(9):442-50. https://doi.org/10.1016/j.tem.2013.05.002
van der Vaart JI, Boon MR, Houtkooper RH. The role of AMPK signaling in brown adipose tissue activation. Cells. 2021;10(5):1122. https://doi.org/10.3390/cells10051122
Villarroya J, Cereijo R, Gavaldà-Navarro A, Peyrou M, Giralt M, Villarroya F. New insights into the secretory functions of brown adipose tissue. J Endocrinol. 2019;243(2):R19-27. https://doi.org/10.1530/JOE-19-0295
Wang N, Liu J, Xie F, Gao X, Ye JH, Sun LY, et al. miR-124/ATF-6, a novel lifespan extension pathway of Astragalus polysaccharide in Caenorhabditis elegans. J Cell Biochem. 2015;116(2):242-51. https://doi.org/10.1002/jcb.24961
Wang N, Zheng J, Chen Z, Liu Y, Dura B, Kwak M, et al. Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nat Commun. 2019;10(1):95. https://doi.org/10.1038/s41467-018-07981-6
Watson RT, Pessin JE. Bridging the GAP between insulin signaling and GLUT4 translocation. Trends Biochem Sci. 2006;31(4):215-22. https://doi.org/10.1016/j.tibs.2006.02.007
Wu Y, Ou-Yang J-P, Wu K, Wang Y, Zhou Y-F, Wen C-Y. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B. Acta Pharmacol Sin. 2005;26(3):345-52. https://doi.org/10.1111/j.1745-7254.2005.00062.x
Zhang R, Qin X, Zhang T, Li Q, Zhang J, Zhao J. Astragalus polysaccharide improves insulin sensitivity via AMPK activation in 3T3-L1 adipocytes. Molecules. 2018;23(10):2711. https://doi.org/10.3390/molecules23102711
Zhao J, Hu J, Zhu M, Du M. Trenbolone enhances myogenic differentiation by enhancing β-catenin signaling in muscle-derived stem cells of cattle. Domest Anim Endocrinol. 2011;40(4):222-9. https://doi.org/10.1016/j.domaniend.2011.01.004
Zheng Y, Ren W, Zhang L, Zhang Y, Liu D, Liu Y. A review of the pharmacological action of Astragalus polysaccharide. Front Pharmacol. 2020;11:349. https://doi.org/10.3389/fphar.2020.00349

Auteurs

Shihe Zhang (S)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Pengkang Song (P)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Xiaoyou Chen (X)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Yu Wang (Y)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Xuyang Gao (X)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Lin Liang (L)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

Junxing Zhao (J)

College of Animal Sciences, Shanxi Agricultural University, Taigu, China.

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