MicroRNA Regulatory Networks as Biomarkers in Obesity: The Emerging Role

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 1617)

Abstract

Even though it is a pandemic health problem worldwide, the pathogenesis of obesity is poorly understood. Recently, emerging studies verified that microRNAs (miRNAs) are involved in complicated metabolic processes including adipocyte differentiation, fat cell formation (adipogenesis), obesity-related insulin resistance and inflammation. Many regulatory networks have been identified in murine adipose tissue, but those in human adipose tissue are not as well known. In addition, miRNAs have been detected in circulation, and thus may be usable as diagnostic indicators. MiRNAs may play an important part in regulating metabolic functions in adipose tissues and, by extension, obesity and its associated disorders. Consequently, they may be potential candidates for therapeutic targets and biomarkers.

Key words

Obesity Adipogenesis Regulatory networks Insulin resistance Biomarkers miRNAs 
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References

  1. 1.
    Haslam DW, James WP (2005) Obesity. Lancet 366(9492):1197–1209. doi: 10.1016/s0140-6736(05)67483-1 CrossRefPubMedGoogle Scholar
  2. 2.
    World Health Organization (2014) Global status report on noncommunicable diseases 2014: attaining the nine global noncommunicable diseases targets; a shared responsibility. World Health Organization, GenevaGoogle Scholar
  3. 3.
    Heneghan HM, Miller N, Kerin MJ (2010) Role of microRNAs in obesity and the metabolic syndrome. Obes Rev 11(5):354–361. doi: 10.1111/j.1467-789X.2009.00659.x CrossRefPubMedGoogle Scholar
  4. 4.
    Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309(5740):1519–1524. doi: 10.1126/science.1111444 CrossRefPubMedGoogle Scholar
  5. 5.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297CrossRefPubMedGoogle Scholar
  6. 6.
    Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294(5543):853–858. doi: 10.1126/science.1064921 CrossRefPubMedGoogle Scholar
  7. 7.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi: 10.1016/j.cell.2009.01.002 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hulsmans M, Holvoet P (2013) MicroRNAs as early biomarkers in obesity and related metabolic and cardiovascular diseases. Curr Pharm Des 19(32):5704–5717CrossRefPubMedGoogle Scholar
  9. 9.
    Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7(12):885–896. doi: 10.1038/nrm2066 CrossRefPubMedGoogle Scholar
  10. 10.
    Mudhasani R, Imbalzano AN, Jones SN (2010) An essential role for Dicer in adipocyte differentiation. J Cell Biochem 110(4):812–816. doi: 10.1002/jcb.22625.
  11. 11.
    Martinelli R, Nardelli C, Pilone V, Buonomo T, Liguori R, Castano I, Buono P, Masone S, Persico G, Forestieri P, Pastore L, Sacchetti L (2010) miR-519d overexpression is associated with human obesity. Obesity (Silver Spring) 18(11):2170–2176. doi: 10.1038/oby.2009.474 CrossRefGoogle Scholar
  12. 12.
    Liu S, Yang Y, Wu J (2011) TNFalpha-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors. Biochem Biophys Res Commun 414(3):618–624. doi: 10.1016/j.bbrc.2011.09.131.
  13. 13.
    Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ (2009) MicroRNA let-7 regulates 3T3-L1 adipogenesis. Mol Endocrinol 23(6):925–931. doi: 10.1210/me.2008-0298 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wang Q, Li YC, Wang J, Kong J, Qi Y, Quigg RJ, Li X (2008) miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci U S A 105(8):2889–2894. doi: 10.1073/pnas.0800178105 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zaragosi LE, Wdziekonski B, Brigand KL, Villageois P, Mari B, Waldmann R, Dani C, Barbry P (2011) Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol 12(7):R64. doi: 10.1186/gb-2011-12-7-r64 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ling HY, Wen GB, Feng SD, Tuo QH, Ou HS, Yao CH, Zhu BY, Gao ZP, Zhang L, Liao DF (2011) MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling. Clin Exp Pharmacol Physiol 38(4):239–246. doi: 10.1111/j.1440–1681.2011.05493.x.
  17. 17.
    Lin Q, Gao Z, Alarcon RM, Ye J, Yun Z (2009) A role of miR-27 in the regulation of adipogenesis. FEBS J 276(8):2348–2358CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T (2010) Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol Endocrinol 24(10):1978–1987. doi: 10.1210/me.2010-0054 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Karbiener M, Fischer C, Nowitsch S, Opriessnig P, Papak C, Ailhaud G, Dani C, Amri EZ, Scheideler M (2009) microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun 390(2):247–251. doi: 10.1016/j.bbrc.2009.09.098 CrossRefPubMedGoogle Scholar
  20. 20.
    Kim YJ, Hwang SJ, Bae YC, Jung JS (2009) MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue. Stem Cells 27(12):3093–3102. doi: 10.1002/stem.235 PubMedGoogle Scholar
  21. 21.
    Tang YF, Zhang Y, Li XY, Li C, Tian W, Liu L (2009) Expression of miR-31, miR-125b-5p, and miR-326 in the adipogenic differentiation process of adipose-derived stem cells. OMICS 13(4):331–336. doi: 10.1089/omi.2009.0017 CrossRefPubMedGoogle Scholar
  22. 22.
    Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, Sun Y, Koo S, Perera RJ, Jain R, Dean NM, Freier SM, Bennett CF, Lollo B, Griffey R (2004) MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279(50):52361–52365. doi: 10.1074/jbc.C400438200 CrossRefPubMedGoogle Scholar
  23. 23.
    Wilfred BR, Wang WX, Nelson PT (2007) Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab 91(3):209–217. doi: 10.1016/j.ymgme.2007.03.011 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Xie H, Lim B, Lodish HF (2009) MicroRNAs induced during adipogenesis that accelerate fat cell development are downregulated in obesity. Diabetes 58(5):1050–1057. doi: 10.2337/db08-1299 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kennell JA, Gerin I, MacDougald OA, Cadigan KM (2008) The microRNA miR-8 is a conserved negative regulator of Wnt signaling. Proc Natl Acad Sci U S A 105(40):15417–15422. doi: 10.1073/pnas.0807763105 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Qin L, Chen Y, Niu Y, Chen W, Wang Q, Xiao S, Li A, Xie Y, Li J, Zhao X, He Z, Mo D (2010) A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC Genomics 11:320. doi: 10.1186/1471-2164-11-320 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ahn J, Lee H, Jung CH, Jeon TI, Ha TY (2013) MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade. EMBO Mol Med 5(10):1602–1612. doi: 10.1002/emmm.201302647.
  28. 28.
    Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, Selimyan R, Egan JM, Smith SR, Fried SK, Gorospe M (2011) miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol Cell Biol 31(4):626–638. doi: 10.1128/mcb.00894-10 CrossRefPubMedGoogle Scholar
  29. 29.
    Enomoto H, Furuichi T, Zanma A, Yamana K, Yoshida C, Sumitani S, Yamamoto H, Enomoto-Iwamoto M, Iwamoto M, Komori T (2004) Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci 117(Pt 3):417–425. doi: 10.1242/jcs.00866 PubMedGoogle Scholar
  30. 30.
    Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner-Strauss JG, Scheideler M (2011) MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol 8(5):850–860. doi: 10.4161/rna.8.5.16153 CrossRefPubMedGoogle Scholar
  31. 31.
    Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28(2):357–364. doi: 10.1002/stem.288 PubMedPubMedCentralGoogle Scholar
  32. 32.
    Guo Y, Chen Y, Zhang Y, Zhang Y, Chen L, Mo D (2012) Up-regulated miR-145 expression inhibits porcine preadipocytes differentiation by targeting IRS1. Int J Biol Sci 8(10):1408–1417. doi: 10.7150/ijbs.4597 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Peng Y, Xiang H, Chen C, Zheng R, Chai J, Peng J, Jiang S (2013) MiR-224 impairs adipocyte early differentiation and regulates fatty acid metabolism. Int J Biochem Cell Biol 45(8):1585–1593. doi: 10.1016/j.biocel.2013.04.029.
  34. 34.
    Xu P, Vernooy SY, Guo M, Hay BA (2003) The drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13(9):790–795CrossRefPubMedGoogle Scholar
  35. 35.
    Teleman AA, Maitra S, Cohen SM (2006) Drosophila lacking microRNA miR-278 are defective in energy homeostasis. Genes Dev 20(4):417–422. doi: 10.1101/gad.374406 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Peng Y, Yu S, Li H, Xiang H, Peng J, Jiang S (2014) MicroRNAs: emerging roles in adipogenesis and obesity. Cell Signal 26(9):1888–1896. doi: 10.1016/j.cellsig.2014.05.006.
  37. 37.
    Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438(7068):685–689. doi: 10.1038/nature04303 CrossRefPubMedGoogle Scholar
  38. 38.
    Takanabe R, Ono K, Abe Y, Takaya T, Horie T, Wada H, Kita T, Satoh N, Shimatsu A, Hasegawa K (2008) Up-regulated expression of microRNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. Biochem Biophys Res Commun 376(4):728–732. doi: 10.1016/j.bbrc.2008.09.050 CrossRefPubMedGoogle Scholar
  39. 39.
    Nakanishi N, Nakagawa Y, Tokushige N, Aoki N, Matsuzaka T, Ishii K, Yahagi N, Kobayashi K, Yatoh S, Takahashi A, Suzuki H, Urayama O, Yamada N, Shimano H (2009) The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun 385(4):492–496. doi: 10.1016/j.bbrc.2009.05.058 CrossRefPubMedGoogle Scholar
  40. 40.
    Kloting N, Berthold S, Kovacs P, Schon MR, Fasshauer M, Ruschke K, Stumvoll M, Bluher M (2009) MicroRNA expression in human omental and subcutaneous adipose tissue. PLoS One 4(3):e4699. doi: 10.1371/journal.pone.0004699 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Zhao E, Keller MP, Rabaglia ME, Oler AT, Stapleton DS, Schueler KL, Neto EC, Moon JY, Wang P, Wang IM, Lum PY, Ivanovska I, Cleary M, Greenawalt D, Tsang J, Choi YJ, Kleinhanz R, Shang J, Zhou YP, Howard AD, Zhang BB, Kendziorski C, Thornberry NA, Yandell BS, Schadt EE, Attie AD (2009) Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice. Mamm Genome 20(8):476–485. doi: 10.1007/s00335-009-9217-2 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Grandjean V, Fourre S, De Abreu DA, Derieppe MA, Remy JJ, Rassoulzadegan M (2015) RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders. Sci Rep 5:18193. doi: 10.1038/srep18193 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lustig Y, Barhod E, Ashwal-Fluss R, Gordin R, Shomron N, Baruch-Umansky K, Hemi R, Karasik A, Kanety H (2014) RNA-binding protein PTB and microRNA-221 coregulate AdipoR1 translation and adiponectin signaling. Diabetes 63(2):433–445. doi: 10.2337/db13-1032 CrossRefPubMedGoogle Scholar
  44. 44.
    Meerson A, Traurig M, Ossowski V, Fleming JM, Mullins M, Baier LJ (2013) Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-alpha. Diabetologia 56(9):1971–1979. doi: 10.1007/s00125-013-2950-9 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Chen YH, Heneidi S, Lee JM, Layman LC, Stepp DW, Gamboa GM, Chen BS, Chazenbalk G, Azziz R (2013) miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes 62(7):2278–2286. doi: 10.2337/db12-0963 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Xiao F, Yu J, Liu B, Guo Y, Li K, Deng J, Zhang J, Wang C, Chen S, Du Y, Lu Y, Xiao Y, Zhang Z, Guo F (2014) A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis. Diabetes 63(8):2631–2642. doi: 10.2337/db13–1689.
  47. 47.
    Hung TM, Ho CM, Liu YC, Lee JL, Liao YR, Wu YM, Ho MC, Chen CH, Lai HS, Lee PH (2014) Up-regulation of microRNA-190b plays a role for decreased IGF-1 that induces insulin resistance in human hepatocellular carcinoma. PLoS One 9(2):e89446. doi: 10.1371/journal.pone.0089446 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kornfeld JW, Baitzel C, Konner AC, Nicholls HT, Vogt MC, Herrmanns K, Scheja L, Haumaitre C, Wolf AM, Knippschild U, Seibler J, Cereghini S, Heeren J, Stoffel M, Bruning JC (2013) Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature 494(7435):111–115. doi: 10.1038/nature11793 CrossRefPubMedGoogle Scholar
  49. 49.
    Yang YM, Seo SY, Kim TH, Kim SG (2012) Decrease of microRNA-122 causes hepatic insulin resistance by inducing protein tyrosine phosphatase 1B, which is reversed by licorice flavonoid. Hepatology 56(6):2209–2220. doi: 10.1002/hep.25912.
  50. 50.
    Zhou B, Li C, Qi W, Zhang Y, Zhang F, Wu JX, Hu YN, Wu DM, Liu Y, Yan TT, Jing Q, Liu MF, Zhai QW (2012) Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity. Diabetologia 55(7):2032–2043. doi: 10.1007/s00125-012-2539-8 CrossRefPubMedGoogle Scholar
  51. 51.
    Li W, Wang J, Chen QD, Qian X, Li Q, Yin Y, Shi ZM, Wang L, Lin J, Liu LZ, Jiang BH (2013) Insulin promotes glucose consumption via regulation of miR-99a/mTOR/PKM2 pathway. PLoS One 8(6):e64924. doi: 10.1371/journal.pone.0064924 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ling HY, Ou HS, Feng SD, Zhang XY, Tuo QH, Chen LX, Zhu BY, Gao ZP, Tang CK, Yin WD, Zhang L, Liao DF (2009) CHANGES IN microRNA (miR) profile and effects of miR-320 in insulin-resistant 3T3-L1 adipocytes. Clin Exp Pharmacol Physiol 36(9):e32–e39. doi: 10.1111/j.1440-1681.2009.05207.x CrossRefPubMedGoogle Scholar
  53. 53.
    Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M (2011) MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 474(7353):649–653. doi: 10.1038/nature10112 CrossRefPubMedGoogle Scholar
  54. 54.
    He A, Zhu L, Gupta N, Chang Y, Fang F (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol 21(11):2785–2794. doi: 10.1210/me.2007-0167 CrossRefPubMedGoogle Scholar
  55. 55.
    Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, Naar AM (2010) MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328(5985):1566–1569. doi: 10.1126/science.1189123 CrossRefPubMedGoogle Scholar
  56. 56.
    Davalos A, Goedeke L, Smibert P, Ramirez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suarez Y, Lai EC, Fernandez-Hernando C (2011) miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A 108(22):9232–9237. doi: 10.1073/pnas.1102281108 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Ryu HS, Park SY, Ma D, Zhang J, Lee W (2011) The induction of microRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes. PLoS One 6(3):e17343. doi: 10.1371/journal.pone.0017343 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Huang B, Qin W, Zhao B, Shi Y, Yao C, Li J, Xiao H, Jin Y (2009) MicroRNA expression profiling in diabetic GK rat model. Acta Biochim Biophys Sin Shanghai 41(6):472–477CrossRefPubMedGoogle Scholar
  59. 59.
    Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J (2011) Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation 124(2):175–184. doi: 10.1161/circulationaha.110.012237 CrossRefPubMedGoogle Scholar
  60. 60.
    D'Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, Rubino M, Carena MC, Spazzafumo L, De Simone M, Micheli B, Biglioli P, Achilli F, Martelli F, Maggiolini S, Marenzi G, Pompilio G, Capogrossi MC (2010) Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 31(22):2765–2773. doi: 10.1093/eurheartj/ehq167 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T (2011) Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 4(4):446–454. doi: 10.1161/circgenetics.110.958975 CrossRefPubMedGoogle Scholar
  62. 62.
    Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31(6):659–666. doi: 10.1093/eurheartj/ehq013 CrossRefPubMedGoogle Scholar
  63. 63.
    Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating MicroRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3(6):499–506. doi: 10.1161/circgenetics.110.957415 CrossRefPubMedGoogle Scholar
  64. 64.
    Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S (2010) Circulating microRNAs in patients with coronary artery disease. Circ Res 107(5):677–684. doi: 10.1161/CIRCRESAHA.109.215566 CrossRefPubMedGoogle Scholar
  65. 65.
    Hulsmans M, Sinnaeve P, Van der Schueren B, Mathieu C, Janssens S, Holvoet P (2012) Decreased miR-181a expression in monocytes of obese patients is associated with the occurrence of metabolic syndrome and coronary artery disease. J Clin Endocrinol Metab 97(7):E1213–E1218. doi: 10.1210/jc.2012-1008 CrossRefPubMedGoogle Scholar
  66. 66.
    Guo M, Mao X, Ji Q, Lang M, Li S, Peng Y, Zhou W, Xiong B, Zeng Q (2010) miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome. Immunol Cell Biol 88(5):555–564. doi: 10.1038/icb.2010.16 CrossRefPubMedGoogle Scholar
  67. 67.
    Hulsmans M, Van Dooren E, Mathieu C, Holvoet P (2012) Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin. PLoS One 7(2):e32794. doi: 10.1371/journal.pone.0032794 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Lihua Zhang
    • 1
  • Daniel Miller
    • 2
  • Qiuping Yang
    • 1
  • Bin Wu
    • 3
  1. 1.Department of GeriatricsFirst Affiliated Hospital of Kunming Medical UniversityKunmingChina
  2. 2.School of ComputingUniversity of South AlabamaMobileUSA
  3. 3.Department of EndocrinologyFirst Affiliated Hospital, Kunming Medical UniversityKunmingChina

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