BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Myonectin inhibits adipogenesis in 3T3-L1 preadipocytes by regulating p38 MAPK pathway

  • Park, Tae-Jun (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Park, Anna (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Kim, Jaehoon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Kim, Jeong-Yoon (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Han, Baek Soo (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Oh, Kyoung-Jin (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Eun Woo (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Sang Chul (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Bae, Kwang-Hee (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Won Kon (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2020.11.26
  • Accepted : 2020.12.04
  • Published : 2021.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

In current times, obesity is a major health problem closely associated with metabolic disease such as diabetes, dyslipidemia, and cardiovascular disease. The direct cause of obesity is known as an abnormal increase in fat cell size and the adipocyte pool. Hyperplasia, the increase in number of adipocytes, results from adipogenesis in which preadipocytes differentiate into mature adipocytes. Adipogenesis is regulated by local and systemic cues that alter transduction pathways and subsequent control of adipogenic transcription factors. Therefore, the regulation of adipogenesis is an important target for preventing obesity. Myonectin, a member of the CTRP family, is a type of myokine released by skeletal muscle cells. Although several studies have shown that myonectin is associated with lipid metabolism, the role of myonectin during adipogenesis is not known. Here, we demonstrate the role of myonectin during adipocyte differentiation of 3T3-L1 cells. We found that myonectin inhibits the adipogenesis of 3T3-L1 preadipocytes with a reduction in the expression of adipogenic transcription factors such as C/EBPα, β and PPARγ. Furthermore, we show that myonectin has an inhibitory effect on adipogenesis through the regulation of the p38 MAPK pathway and CHOP. These findings suggest that myonectin may be a novel therapeutic target for the prevention of obesity.

Keywords

References

  1. Spiegelman BM and Flier JS (2001) Obesity and the regulation of energy balance. Cell 104, 531-543 https://doi.org/10.1016/S0092-8674(01)00240-9
  2. Arner P and Spalding KL (2010) Fat cell turnover in humans. Biochem Biophys Res Commun 396, 101-104 https://doi.org/10.1016/j.bbrc.2010.02.165
  3. Seldin MM, Peterson JM, Byerly MS, Wei Z and Wong GW (2012) Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 287, 11968-11980 https://doi.org/10.1074/jbc.M111.336834
  4. Mi Q, Li Y, Wang M et al (2019) Circulating C1q/TNF-related protein isoform 15 is a marker for the presence of metabolic syndrome. Diabetes Metab Res Rev 35, e3085 https://doi.org/10.1002/dmrr.3085
  5. Farmer SR (2006) Transcriptional control of adipocyte formation. Cell Metab 4, 263-273 https://doi.org/10.1016/j.cmet.2006.07.001
  6. Chang E and Kim CY (2019) Natural products and obesity: a focus on the regulation of mitotic clonal expansion during Adipogenesis. Molecules 24, 1157 https://doi.org/10.3390/molecules24061157
  7. Rosen ED and MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7, 885-896 https://doi.org/10.1038/nrm2066
  8. Koh YK, Lee MY, Kim JW et al (2008) Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2. J Biol Chem 283, 34896-34906 https://doi.org/10.1074/jbc.M804007200
  9. Takeuchi K and Reue K (2009) Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 296, E1195-1209 https://doi.org/10.1152/ajpendo.90958.2008
  10. Jones JR, Barrick C, Kim KA et al (2005) Deletion of PPAR gamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci U S A 102, 6207-6212 https://doi.org/10.1073/pnas.0306743102
  11. Tang QQ, Zhang JW and Daniel Lane M (2004) Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis. Biochem Biophys Res Commun 319, 235-239 https://doi.org/10.1016/j.bbrc.2004.04.176
  12. Darlington GJ, Wang N and Hanson RW (1995) C/EBP alpha: a critical regulator of genes governing integrative metabolic processes. Curr Opin Genet Dev 5, 565-570 https://doi.org/10.1016/0959-437X(95)80024-7
  13. Koerner A, Kratzsch J and Kiess W (2005) Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come. Best Pract Res Clin Endocrinol Metab 19, 525-546 https://doi.org/10.1016/j.beem.2005.07.008
  14. Kim H and Sakamoto K (2012) (-)-Epigallocatechin gallate suppresses adipocyte differentiation through the MEK/ERK and PI3K/Akt pathways. Cell Biol Int 36, 147-153 https://doi.org/10.1042/CBI20110047
  15. Hardie DG (2011) AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 25, 1895-1908 https://doi.org/10.1101/gad.17420111
  16. Huang B, Yuan HD, Kim DY, Quan HY and Chung SH (2011) Cinnamaldehyde prevents adipocyte differentiation and adipogenesis via regulation of peroxisome proliferatoractivated receptor-gamma (PPARgamma) and AMP-activated protein kinase (AMPK) pathways. J Agric Food Chem 59, 3666-3673 https://doi.org/10.1021/jf104814t
  17. Nakae J, Kitamura T, Kitamura Y, Biggs WH 3rd, Arden KC and Accili D (2003) The forkhead transcription factor Foxo1 regulates adipocyte differentiation. Dev Cell 4, 119-129 https://doi.org/10.1016/S1534-5807(02)00401-X
  18. Chen YY, Lee MH, Hsu CC, Wei CL and Tsai YC (2012) Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathway in 3T3-L1 preadipocytes. J Agric Food Chem 60, 955-963 https://doi.org/10.1021/jf203981x
  19. Bennett CN, Ross SE, Longo KA et al (2002) Regulation of Wnt signaling during adipogenesis. J Biol Chem 277, 30998-31004 https://doi.org/10.1074/jbc.M204527200
  20. Kim WK, Choi HR, Park SG, Ko Y, Bae KH and Lee SC (2012) Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated beta-catenin stabilization. Int J Biochem Cell Biol 44, 327-334 https://doi.org/10.1016/j.biocel.2011.11.004
  21. Bost F, Aouadi M, Caron L and Binetruy B (2005) The role of MAPKs in adipocyte differentiation and obesity. Biochimie 87, 51-56 https://doi.org/10.1016/j.biochi.2004.10.018
  22. Pearson G, Robinson F, Beers Gibson T et al (2001) Mitogenactivated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22, 153-183 https://doi.org/10.1210/er.22.2.153
  23. Johnson GL and Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912 https://doi.org/10.1126/science.1072682
  24. Hu J, Roy SK, Shapiro PS et al (2001) ERK1 and ERK2 activate CCAAAT/enhancer-binding protein-beta-dependent gene transcription in response to interferon-gamma. J Biol Chem 276, 287-297 https://doi.org/10.1074/jbc.M004885200
  25. Zick Y (2001) Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol 11, 437-441 https://doi.org/10.1016/S0962-8924(01)81297-6
  26. Hirosumi J, Tuncman G, Chang L et al (2002) A central role for JNK in obesity and insulin resistance. Nature 420, 333-336 https://doi.org/10.1038/nature01137
  27. Engelman JA, Lisanti MP and Scherer PE (1998) Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem 273, 32111-32120 https://doi.org/10.1074/jbc.273.48.32111
  28. Hata K, Nishimura R, Ikeda F et al (2003) Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Mol Biol Cell 14, 545-555 https://doi.org/10.1091/mbc.E02-06-0356
  29. Engelman JA, Berg AH, Lewis RY, Lin A, Lisanti MP and Scherer PE (1999) Constitutively active mitogen-activated protein kinase kinase 6 (MKK6) or salicylate induces spontaneous 3T3-L1 adipogenesis. J Biol Chem 274, 35630-35638 https://doi.org/10.1074/jbc.274.50.35630
  30. Ho IC, Kim JH, Rooney JW, Spiegelman BM and Glimcher LH (1998) A potential role for the nuclear factor of activated T cells family of transcriptional regulatory proteins in adipogenesis. Proc Natl Acad Sci U S A 95, 15537-15541 https://doi.org/10.1073/pnas.95.26.15537
  31. Patel NG, Holder JC, Smith SA, Kumar S and Eggo MC (2003) Differential regulation of lipogenesis and leptin production by independent signaling pathways and rosiglitazone during human adipocyte differentiation. Diabetes 52, 43-50 https://doi.org/10.2337/diabetes.52.1.43
  32. Aouadi M, Laurent K, Prot M, Le Marchand-Brustel Y, Binetruy B and Bost F (2006) Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages. Diabetes 55, 281-289 https://doi.org/10.2337/diabetes.55.02.06.db05-0963
  33. Yang TT, Xiong Q, Enslen H, Davis RJ and Chow CW (2002) Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases. Mol Cell Biol 22, 3892-3904 https://doi.org/10.1128/MCB.22.11.3892-3904.2002
  34. Tamura K, Sudo T, Senftleben U, Dadak AM, Johnson R and Karin M (2000) Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis. Cell 102, 221-231 https://doi.org/10.1016/S0092-8674(00)00027-1
  35. Wang XZ and Ron D (1996) Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD 153) by p38 MAP Kinase. Science 272, 1347-1349 https://doi.org/10.1126/science.272.5266.1347
  36. Batchvarova N, Wang XZ and Ron D (1995) Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153). EMBO J 14, 4654-4661 https://doi.org/10.1002/j.1460-2075.1995.tb00147.x
  37. Kim WK, Lee CY, Kang MS et al (2008) Effects of leptin on lipid metabolism and gene expression of differentiationassociated growth factors and transcription factors during differentiation and maturation of 3T3-L1 preadipocytes. Endocr J 55, 827-837 https://doi.org/10.1507/endocrj.K08E-115
  38. Kim WK, Jung H, Kim DH et al (2009) Regulation of adipogenic differentiation by LAR tyrosine phosphatase in human mesenchymal stem cells and 3T3-L1 preadipocytes. J Cell Sci 122, 4160-4167 https://doi.org/10.1242/jcs.053009
  39. Kim EY, Kim WK, Kang HJ et al (2012) Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity. J Lipid Res 53, 1864-1876 https://doi.org/10.1194/jlr.M026567
  40. Hossain M, Imran KM, Rahman MS, Yoon D, Marimuthu V, Kim YS (2020) Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes. BMB Rep 53, 142-147 https://doi.org/10.5483/BMBRep.2020.53.3.093
  41. Nguyen MT, Min KH & Lee W (2020) MiR-183-5p induced by saturated fatty acids regulates the myogenic differentiation by directly targeting FHL1 in C2C12 myoblasts. BMB Rep 53, 605-610 https://doi.org/10.5483/BMBRep.2020.53.11.175