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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Potential involvement of Drosophila flightless-1 in carbohydrate metabolism

  • Park, Jung-Eun (Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Jang, Jinho (Department of Biological Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology) ;
  • Lee, Eun Ji (Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Su Jung (Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yoo, Hyun Ju (Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Semin (Department of Biological Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology) ;
  • Kang, Min-Ji (Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center)
  • Received : 2018.07.10
  • Accepted : 2018.07.25
  • Published : 2018.09.30
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Abstract

A previous study of ours indicated that Drosophila flightless-1 controls lipid metabolism, and that there is an accumulation of triglycerides in flightless-1 (fliI)-mutant flies, where this mutation triggers metabolic stress and an obesity phenotype. Here, with the aim of characterizing the function of FliI in metabolism, we analyzed the levels of gene expression and metabolites in fliI-mutant flies. The levels of enzymes related to glycolysis, lipogenesis, and the pentose phosphate pathway increased in fliI mutants; this result is consistent with the levels of metabolites corresponding to a metabolic pathway. Moreover, high-throughput RNA sequencing revealed that Drosophila FliI regulates the expression of genes related to biological processes such as chromosome organization, carbohydrate metabolism, and immune reactions. These results showed that Drosophila FliI regulates the expression of metabolic genes, and that dysregulation of the transcription controlled by FliI gives rise to metabolic stress and problems in the development and physiology of Drosophila.

Keywords

References

  1. Campbell HD, Schimansky T, Claudianos C et al (1993) The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans. Proc Natl Acad Sci U S A 90, 11386-11390 https://doi.org/10.1073/pnas.90.23.11386
  2. Archer SK, Behm CA, Claudianos C and Campbell HD (2004) The flightless I protein and the gelsolin family in nuclear hormone receptor-mediated signalling. Biochem Soc Trans 32, 940-942 https://doi.org/10.1042/BST0320940
  3. Ghoshdastider U, Popp D, Burtnick LD and Robinson RC (2013) The expanding superfamily of gelsolin homology domain proteins. Cytoskeleton (Hoboken) 70, 775-795 https://doi.org/10.1002/cm.21149
  4. Nag S, Larsson M, Robinson RC and Burtnick LD (2013) Gelsolin: the tail of a molecular gymnast. Cytoskeleton (Hoboken) 70, 360-384 https://doi.org/10.1002/cm.21117
  5. Cowin AJ, Adams DH, Strudwick XL et al (2007) Flightless I deficiency enhances wound repair by increasing cell migration and proliferation. J Pathol 211, 572-581 https://doi.org/10.1002/path.2143
  6. Lee YH, Campbell HD and Stallcup MR (2004) Developmentally essential protein flightless I is a nuclear receptor coactivator with actin binding activity. Mol Cell Biol 24, 2103-2117 https://doi.org/10.1128/MCB.24.5.2103-2117.2004
  7. Wu L, Chen H, Zhu Y et al (2013) Flightless I homolog negatively regulates ChREBP activity in cancer cells. Int J Biochem Cell Biol 45, 2688-2697 https://doi.org/10.1016/j.biocel.2013.09.004
  8. Lee YH and Stallcup MR (2006) Interplay of Fli-I and FLAP1 for regulation of beta-catenin dependent transcription. Nucleic Acids Res 34, 5052-5059 https://doi.org/10.1093/nar/gkl652
  9. Choi JS, Choi SS, Kim ES et al (2015) Flightless-1, a novel transcriptional modulator of PPARgamma through competing with RXRalpha. Cell Signal 27, 614-620 https://doi.org/10.1016/j.cellsig.2014.11.035
  10. Jeong KW, Lee YH and Stallcup MR (2009) Recruitment of the SWI/SNF chromatin remodeling complex to steroid hormone-regulated promoters by nuclear receptor coactivator flightless-I. J Biol Chem 284, 29298-29309 https://doi.org/10.1074/jbc.M109.037010
  11. Park JE, Lee EJ, Kim JK, Song Y, Choi JH and Kang MJ (2018) Flightless-I Controls Fat Storage in Drosophila. Mol Cells 41, 603-611
  12. Church C, Moir L, McMurray F et al (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42, 1086-1092 https://doi.org/10.1038/ng.713
  13. Bray GA and Popkin BM (1998) Dietary fat intake does affect obesity! Am J Clin Nutr 68, 1157-1173 https://doi.org/10.1093/ajcn/68.6.1157
  14. de Couet HG, Fong KS, Weeds AG, McLaughlin PJ and Miklos GL (1995) Molecular and mutational analysis of a gelsolin-family member encoded by the flightless I gene of Drosophila melanogaster. Genetics 141, 1049-1059
  15. Perrimon N, Smouse D and Miklos GL (1989) Developmental genetics of loci at the base of the X chromosome of Drosophila melanogaster. Genetics 121, 313-331
  16. Frederiks WM, Bosch KS, De Jong JS and Van Noorden CJ (2003) Post-translational regulation of glucose-6-phosphate dehydrogenase activity in (pre)neoplastic lesions in rat liver. J Histochem Cytochem 51, 105-112 https://doi.org/10.1177/002215540305100112
  17. Ishikawa E, Ogushi S, Ishikawa T and Uyeda K (1990) Activation of mammalian phosphofructokinases by ribose 1,5-bisphosphate. J Biol Chem 265, 18875-18878
  18. Zlobine I, Gopal K and Ussher JR (2016) Lipotoxicity in obesity and diabetes-related cardiac dysfunction. Biochim Biophys Acta 1860, 1555-1568
  19. Bandyopadhyay GK, Yu JG, Ofrecio J and Olefsky JM (2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55, 2277-2285 https://doi.org/10.2337/db06-0062
  20. Bernal A and Kimbrell DA (2000) Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity. Proc Natl Acad Sci U S A 97, 6019-6024 https://doi.org/10.1073/pnas.100391597
  21. Andersen JS, Lam YW, Leung AK et al (2005) Nucleolar proteome dynamics. Nature 433, 77-83 https://doi.org/10.1038/nature03207
  22. Clapier CR, Iwasa J, Cairns BR and Peterson CL (2017) Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol 18, 407-422 https://doi.org/10.1038/nrm.2017.26
  23. Zhang Z, Wang J, Schultz N et al (2014) The HP1 homolog rhino anchors a nuclear complex that suppresses piRNA precursor splicing. Cell 157, 1353-1363 https://doi.org/10.1016/j.cell.2014.04.030
  24. Veal E, Eisenstein M, Tseng ZH and Gill G (1998) A cellular repressor of E1A-stimulated genes that inhibits activation by E2F. Mol Cell Biol 18, 5032-5041 https://doi.org/10.1128/MCB.18.9.5032
  25. Lin R, Elf S, Shan C et al (2015) 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling. Nat Cell Biol 17, 1484-1496 https://doi.org/10.1038/ncb3255
  26. Zimmermann R, Haemmerle G, Wagner EM, Strauss JG, Kratky D and Zechner R (2003) Decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone-sensitive lipase-deficient white adipose tissue. J Lipid Res 44, 2089-2099 https://doi.org/10.1194/jlr.M300190-JLR200
  27. Al-Dwairi A, Pabona JM, Simmen RC and Simmen FA (2012) Cytosolic malic enzyme 1 (ME1) mediates high fat diet-induced adiposity, endocrine profile, and gastrointestinal tract proliferation-associated biomarkers in male mice. PLoS One 7, e46716 https://doi.org/10.1371/journal.pone.0046716
  28. Petridou A, Chatzinikolaou A, Avloniti A et al (2017) Increased Triacylglycerol Lipase Activity in Adipose Tissue of Lean and Obese Men During Endurance Exercise. J Clin Endocrinol Metab 102, 3945-3952 https://doi.org/10.1210/jc.2017-00168
  29. Stofkova A, Krskova K, Vaculin S and Jurcovicova J (2016) Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat correlates with higher production of epinephrine in mesenteric adipocytes in rat model of cachectic rheumatoid arthritis. Autoimmunity 49, 268-276 https://doi.org/10.3109/08916934.2016.1164145
  30. Kim SJ, Tang T, Abbott M, Viscarra JA, Wang Y and Sul HS (2016) AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue. Mol Cell Biol 36, 1961-1976 https://doi.org/10.1128/MCB.00244-16
  31. Choi SW, Lee KS, Lee JH et al (2016) Suppression of Akt-HIF-$1{\alpha}$ signaling axis by diacetyl atractylodiol inhibits hypoxia-induced angiogenesis. BMB Rep 49, 508-513 https://doi.org/10.5483/BMBRep.2016.49.9.069