Regulasi Adipogenesis oleh mTORC1 melalui Jalur ST A T3

Authors

  • Triawanti Triawanti Laboratorium Biokimia Fakultas Kedokteran Universitas Lambung Mangkurat Banjarmasin
  • M Rasjad Indra Laboratorium Fisiologi Fakultas Kedokteran Universitas Brawijaya Malang
  • Askandar Tjokroprawiro Pusat Diabetes dan Nutrisi Surabaya (PDNS) Fakultas Kedokteran Universitas Airlangga/Rumah Sakit Umum Daerah Dr . Soetomo Surabaya
  • Hidayat Sujuti Laboratarium Biokimia-Biomolekuler Fakultas Kedokteran Universitas Brawijaya Malang

DOI:

https://doi.org/10.21776/ub.jkb.2013.027.03.1

Abstract

Obesitas  merupakan  suatu  penyakit  kelebihan  massa  lemak  tubuh  yang  mempunyai  efek  merugikan  bagi  kesehatan.  Pada saat  ini  proses  adipogenesis  menjadi salah  satu  target  terapi  obesitas.  Salah  satu  jalur  yang  diduga  teraktivasi  pada  proses adipogenesis  adalah  melalui aktivasi  ST A T3  yang  salah  satu  jalur  hulunya  melalui protein  mammalian target  of rapamycin complex 1 (mTOR). Penelitian ini bertujuan untuk membuktikan proses adipogenesis melalui jalur ST A T3 yang diaktivasi oleh  mTORC1.  Penelitian  ini  merupakan  penelitian  eksperimental  dengan  rancangan  post  test  only  control.  Untuk penghambatan  mTORC1  digunakan  rapamycin  dan  penghambatan  ST A T3  digunakan  inhibitor  ST A T3  peptide.  Subjek penelitian  adalah  kultur  primer  sel  preadiposit  yang  diambil  dari  lemak  viseral  tikus  putih  Rattus  norvegicus.  Setelah  kultur sel preadiposit dinilai konfluen minimal 70-80% dilakukan induksi diferensiasi dan dibagi menjadi  4 kelompok yakni (K) kontrol  (A):   diberi rapamycin  10  nM,  (B):  diberi  inhibitor  ST A T3  100  µM (C):  diberi  inhibitor  ST A T3  100  µM dan   rapamycin10  nM.  Parameter  yang  diukur  adalah  aktivasi  p70S6K1,  ST A T3,  ekspresi  C/EBPδ,  aktivitas  enzim  Glyserol-3-fosfodehidrogenase  (GPDH)  pada  hari  ke-2,  ke-4  dan  ke-6  serta  gambaran  morfologis  sel  adiposit.  Analisis  statistik menggunakan uji ANOVA, Duncan dan korelasi Pearson dengan tingkat kepercayaan 95%. Hasil penelitian membuktikan terjadi  penghambatan  proses  adipogenesis  karena  penghambatan  aktivasi  p70S6K1,  dan  ST A T3  oleh  rapamycin  dan inhibitor ST A T3.

Downloads

Download data is not yet available.

References

Dewan S and Wilding JP. Obesity and Type-2 Diabetes in the Elderly. Gerontology. 2003; 49(3): 137-145.

WHO. Obesity and Overweight. (Online) 2006. http://www.who.int/mediacentre/factsheets/fs311/en/ [diakses tanggal 23 Juli 2009].

Kemenkes RI. Hasil Riset Kesehatan Dasar. Jakarta: Badan Pengembangan dan Penelitian Kesehatan; 2010.

Departemen Kesehatan Republik Indonesia. Laporan Hasil Riset Kesehatan Dasar Nasional. Jakarta: Badan Penelitian dan Pengembangan Kesehatan; 2008.

Stein CJ and Colditz. The Epidemic of Obesity. The Journal of Clinical Endocrinology and Metabolism. 2004; 89(6): 2522-2525.

De Simone G, Di Fiore A, and Supuran CT. Are Carbonic Anhydrase Inhibitors Suitable for Obtaining Antiobesity Drugs? Current Pharmaceutical Design. 2008; 14(7): 655-660.

Jang EH, Moon JS, Ko JH, et al. Novel Black Soy Peptides with Antiobesity Effects: Activation of Leptin-Like Signaling and AMP-Activated Protein Kinase. International Journal of Obesity. 2008; 32(7): 1161-1170.

Musri MM, Gomis R, and Parrizas M. Chromatin and Chromatin-Modifying Proteins in Adipogenesis. Biochemistry and Cell Biology. 2007; 85(4): 397-410.

Au WS, Payne VA, O'rahilly S, and Rochford JJ. The NR4A Family of Orphan Nuclear Receptors are Not Required for Adipogenesis. International Journal of Obesity. 2008; 32: 388-392

Zhang JW, Klemm DJ, Vinson C, and Lane MD. Role of CREB in Transcriptionl Regulation of CCAA T/Enhancer-Binding Protein Î’ Gene During Adipogenesis. The Journal Biological Chemistry. 2004; 279(6): 4471-4478.

Bacquer O, Petroulakis E, Pagllalunga S, et al. Elevated Sensitivity to Diet-Induced Obesity and Insulin Resistance in Mice Lacking 4E-BP1 dan 4E-BP2. Journal of Clinical Investigation. 2007; 117(2): 387-396.

Rui L. A Link Between Protein Translation and Body Weight. The Journal of Clinical Investigation. 2007; 117(2): 310-313.

Hwang M, Perez CA, Moretti L, and Lu B. The mTOR Signaling Network: Insights from its Role During Embryonic Development. Current Medicinal Chemistry. 2008; 15(12): 1192-1208.

Kahn BB and Myers MG Jr. mTOR Tells the Brain that the Body is Hungr. Nature Medicine. 2006; 12(6): 615-617.

Dann SG, Selveraj A, and Thomas G. Mtor Complex1-S6K1 Signaling: At the Crossroads of Obesity, Diabetes and Cancer. Trends in Molecular Medicine. 2007; 13(6): 252-259.

Rosner M and Hengstschlager M. Cytoplasmic and Nuclear Distribution of the Protein Complexes mTORC 1 and mTORC 2: Rapamycin Triggers Dephosphorylation and Delocalization of the mTORC2 Component Rictor and sin1. Human Molecular Genetics. 2008; 17(19): 2934-2948.

El-Chaar D, Gagnon A, and Sorisky A. Inhibition of Insulin Signaling and Adipogenesis by Rapamycin: Effect on Phosphorylation of P70 S6 Kinase Vs Eif4e-BP1. International Journal of Obesity and Related Metabolic Disorders. 2004; 28(2): 191-198.

Kim JE and Chen J. Regulation of Peroxisome Proliferation-Activated Receptor-Gamma Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis. Diabetes. 2004; 53(11): 2748-2756.

Indra MR, Hernowati TE, Satuman, dan Widodo E. Kultur Adiposit dan Pemeriksaan Adiposi tokin. Malang: Laboratorium Ilmu Faal Fakultas Kedokteran Universitas Brawijaya; 2010.

LiuL, LiF, Cardelli JA, Martin KA, Blenis J, and Huang S. Rapamycin Inhibits Cell Motility by Suppression of mTOR-Mediated S6K1 and 4E-BP1 Pathways.Oncogene. 2006; 25(53): 7029-7040.

De Virgilio C and Loewith R. Cell Growth Control: Little Eukaryotes Make Big Contributions. Oncogene. 2006; 25(48): 6392-6415.

Garcia R, Bowman TL, Niu G, et al. Constitutive Activation of Stat3 by the Src and JAK Tyrosine Kinases Participates in Growth Regulation of Human Breast Carcinoma Cells. Oncogene. 2001; 20(20): 2499-2513.

Chen C-L, Hsieh F-C, Lieblein JC, et al. Stat3 Activation in Human Endometrial and Cervical Cancers. British Journal of Cancer. 2007; 96(4): 591-599.

Schust J, Sperl B, Hollis A, Mayer TU, and Berg T. Stattic: A Small-Molecule Inhibitor of STAT3 Activation and Dimerization. Chemistry and Biology. 2006; 13(11): 1235-1242.

Deng J, Grande F, and Neamati N. Small Molecule Inhibitors of Stat3 Signaling Pathway. Current Cancer Drug Targets. 2007; 7(1): 91-107.

Wang D, Zhou Y, Lei W, et al. Signal Transducer and Activator of Transcription 3 (STAT3) Regulates Adipocyte Differentiation Via Peroxisome-Proliferator-Activated Receptor γ (PP ARγ). Biology of Cell. 2009; 102(1): 1-12.

Ma J, Meng Y, Kwiatkowski DJ, et al. Mammalian Target of Regulates Murine and Human Sell Differentiation through STAT3/P63/Jagged/Notch Cascade. Journal of Clinical Investigation. 2010; 120(10): 103-114.

He ML, Wang Y, You JS, Mir PS, and McAllister TA. Effect of Seaweed Extract on Fatty Acid Accumulation and Glycerol-3-Phosphate Dehydrogenase Activity in 3T3-L1-Adipocytes. Journal of Lipid Research. 2009; 44(2): 125-132.

Downloads

Published

2013-04-27

Issue

Section

Research Article

Most read articles by the same author(s)