The role of Fatty acid binding protein 5 (Fabp5) in fatty acid partitioning in the liver

간에서 지방산 분할에 대한 지방산결합 단백질 5의 역할

  • Received : 2019.05.23
  • Accepted : 2019.08.20
  • Published : 2019.08.28


The aim of investigated the role of FABP5 in the hepatic lipogenesis and lipid metabolisms. Mice were overexpressed and silenced liver FABP5 using virus particles. Mice were fed a Western-type diet or regular chow for 1week and then sacrificed mouse after 24hr fasted. Liver homogenates were used for protein analysis by Western blot and mRNA levels by RT-PCR. Hepatic and serum lipids were analysed by thin-layer chromatography. Mice fed a Western-type or high saturated fat diet revealed large increases in FABP5 expression. However, FABP5 mRNA levels were drastically reduced under fasted. Hepatic TG was significantly increased FABP5-OEAV mice, but a significantly decreased hepatic free cholesterol under fed. The discovered a substantial decrease in hepatic TG mass with FABP5 silencing. In these data, presented evidence for an important role of FABP5 in hepatic lipogenesis and hepatic TG storage. FABP5 may also be a potential target in the treatment of NAFLD, metabolic syndrome, and obesity. Furthermore, studies to which transcription factors are involved in FABP5 expression and regulation.


Fatty acid binding protein 5(FABP5);hepatic lipogenesis;non-alcoholic fatty liver disease(NAFLD);metabolic syndrome;obesity


  1. G. V. Richieri, R. T. Ogata & A. M. Kleinfeld. (1994). Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB. The Journal of Biological Chemistry, 269(39), 23918-23930. PMID: 7929039
  2. A. Reese-wagoner, J. Thompson & L. Banaszak. (1999). Structural properties of the adipocyte lipid binding protein. Biochimca et Biophysica Acta, 1441(2-3), 106-116. DOI: 10.1016/S1388-1981(99)00154-7
  3. J. Thompson, J. Ory, A. Reese-wagoner & L. Banaszak. (1999a). The liver fatty acid binding protein-comparison of cavity properties of intracellular lipid-binding proteins. Molecular and Cellular Biochemistry, 192(1-2), 9-16. PMID: 10331654
  4. J. Thompson, A. Reese-wagoner & L. Banaszak. (1999b). Liver fatty acid binding protein: species variation and the accommodation of different ligands. Biochimca et Biophysica Acta 1441(2-3), 117-130. DOI: 10.1016/s1388-1981(99) 00146-8
  5. M. Furuhashi & G. S. Hotamisligil. (2008). Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nature Reviews Drug Discovery 7(6), 489-503. DOI: 10.1038/ nrd2589
  6. L. Makowski & G. S. Hotamisligil. (2005). The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis. Current opinion in lipidology 16(5), 543-548. PMID: 16148539
  7. E. P. Newberry, Y. Xie, S. M. Kennedy, J. Luo & N. O. Davidson. (2006). Protection against Western diet-induced obesity and hepatic steatosis in liver fatty acid-binding protein knockout mice. Hepatology, 44(5), 1191-1205. DOI: 10.1002/hep.21369
  8. E. P. Newberry, S. M. Kennedy, Y. Xie, B. T. Sternard, J. Luo & N. O. Davidson. (2008). Diet-induced obesity and hepatic steatosis in L-Fabp / mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation. American Journal of Physiology Gastrointestinal and Liver Physiology, 294(1), G307-314. DOI: 10.1152/ajpgi. 00377.2007
  9. G. Siegenthaler, R. Hotz, D. Chatellard-Gruaz, L. Didierjean, U. Hellman, & J. H. Saurat. (1994). Purification and characterization of the human epidermal fatty acid-binding protein: localization during epidermal cell differentiation in vivo and in vitro. Biochemical Journal, 302(Pt 2), 363-371. DOI: 10.1042/bj3020363
  10. D. A. Bernlohr, M. A. Simpson, A. V. Hertzel, & L. J. Banaszak. (1997). Intracellular lipid-binding proteins and their genes. Annual Review of Nutrition, 17, 277-303. DOI: 10.1146/annurev.nutr.17.1.277
  11. J. amulin, I. Berget, S. Lien, & H. Sundvold. (2008). Differential gene expression of fatty acid binding proteins during porcine adipogenesis. Comparative Biochemistry and Physiology. Part B, Biochemical & Molecular Biolology, 151(2), 147-152. DOI: 10.1016/j.cbpb.2008. 06.010.
  12. N. H. Haunerland & F. Spener. (2004). Fatty acid-binding proteins--insights from genetic manipulations. Progress in Lipid Research, 43(4), 328-349. DOI: 10.1016/j.plipres.2004.05.001
  13. F. Guthmann, C. Schachtrup, A. Tolle, H. Wissel, B. Binas, H. Kondo, Y. Owada, F. Spener & B. Rustow. (2004). Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma. Biochimca et Biophysica Acta, 1636(2-3), 196-204. DOI: 10.1016/j.bbalip.2003.10.015
  14. Y. Owada, H. Takano, H. Yamanaka, H. Kobayashi, Y. Sugitani, Y. Tomioka, I. Suzuki, R. Suzuki, T. Terui, M. Mizugaki, H. Tagami, T. Noda & H. KONDO. (2002b). Altered water barrier function in epidermal-type fatty acid binding protein-deficient mice. The Journal of Investigative Dermatology, 118(3), 430-435. DOI: 10.1046/j.0022-202x.2001.01616.x
  15. M. Hoekstra, M. Stitzinger, E. J. Van Wanrooij, I. N. Michon, J. K. Kruijt, J. Kamphorst, M. Van Eck, E. Vreugdenhil, T. J. Van Berkel & J. Kuiper. (2006). Microarray analysis indicates an important role for FABP5 and putative novel FABPs on a Western-type diet. Journal of Lipid Research, 47(10), 2198-2207. DOI: 10.1194/ jlr.M600095-JLR200
  16. J. Westerbacka, M. Kolak, T. Kiviluoto, P. Arkkila, J. Siren, A. Hamsten, R. M. Fisher & H. Yki-Jarvinen. (2007). Genes involved in fatty acid partitioning and binding, lipolysis, monocyte/macrophage recruitment, and inflammation are overexpressed in the human fatty liver of insulin-resistant subjects. Diabetes, 56(11), 2759-2765. DOI: 10.2337/db07-0156
  17. A. W. Thorburn, L. H. Storlien, A. B. Jenkins, S. Khouri & E. W. Kraegen. (1989). Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. The American Journal of Clinical Nutrition, 49(6), 1155-1163. DOI: 10.1093/ajcn/49.6.1155
  18. S. R. Witting, M. Brown, R. Saxena, S. Nabinger & N. Morral. (2008). Helper-dependent Adenovirus-mediated Short Hairpin RNA Expression in the Liver Activates the Interferon Response. The Journal of Biological Chemistry, 283(4), 2120-2128. DOI: 10.1074/jbc.M704178200
  19. K. A. Le & L. Tappy. (2006). Metabolic effects of fructose. Current Opinion in Clinical Nutrition and Metabolic Care, 9(4), 469-475. DOI: 10.1097/01.mco.0000232910.61612.4d
  20. N. Morral, H. J. Edenberg, S. R. Witting, J. Altomonte, T. Chu & M. Brown. (2007). Effects of glucose metabolism on the regulation of genes of fatty acid synthesis and triglyceride secretion in the liver. Journal of Lipid Research ,48(7), 1499-1510. DOI: 10.1194/jlr.M700090- JLR200
  21. K. L. Stanhope & P. J. Havel. (2008). Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Current opinion in lipidology, 19(1), 16-24. DOI: 10.1097/ MOL.0b013e3282f2b24a
  22. K. N. Maxwell, R. E. Soccio, E. M. Duncan, E. Sehayek & J. L. Breslow. (2003). Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. Journal of Lipid Research, 44(11), 2109-2119. DOI: 10.1194/jlr.M300203- JLR200
  23. R. J. Mason, T. Pan, K. E. Edeen, L. D. Nielsen, F. Zhang, M. Longphre, M. R. Eckart & S. Neben. (2003). Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells. Journal of Clinical Investigation, 112(2), 244-255. DOI: 10.1172/JCI16793
  24. Y. Chang, K. Edeen, X. Lu, M. De Leon & R. J. Mason. (2006). Keratinocyte growth factor induces lipogenesis in alveolar type II cells through a sterol regulatory element binding protein-1c-dependent pathway. American Journal of Respiratory Cell and Molecular Biology, 35(2), 268-274. DOI: 10.1165/rcmb.2006-0037OC
  25. J. S. Millar, S. J. Stone, U. J. Tietge, B. Tow, J. T. Billheimer, J. S. Wong, R. L. Hamilton, R. V. JR. Farese & D. J. Rader. (2006). Short-term overexpression of DGAT1 or DGAT2 increases hepatic triglyceride but not VLDL triglyceride or apoB production. J Lipid Res, 47(10), 2297-2305. DOI: 10.1194/jlr.M600213 -JLR200
  26. X. X. Yu, S. F. Murray, S. K. Pandey, S. L. Booten, D. Bao, X. Z. Song, S. Kelly, S. Chen, R. Mckay, B. P. Monia & S. Bhanot. (2005). Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice. Hepatology, 42(2), 362-371. DOI: 10.1002/hep.20783
  27. W. C. Man, M. Miyazaki, K. Chu & J. Ntambi. (2006). Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis. Journal of Lipid Research, 47(9), 1928-1939. DOI: 10.1194/jlr.M600172-JLR200
  28. J. Storch & A. E. Thumser. (2000). The fatty acid transport function of fatty acid-binding proteins. Biochimca et Biophysica Acta, 1486(1), 28-44. DOI: 10.1016/s1388-1981(00)00046-9
  29. K. T. Hsu & J. Storch. (1996). Fatty acid transfer from liver and intestinal fatty acid-binding proteins to membranes occurs by different mechanisms. The Journal of Biological Chemistry, 271(23), 13317-13323. DOI: 10.1074/ jbc.271.23.13317
  30. H. Y. Koo, M. A. Wallig, B. H. Chung, T. Y. Nara, B. H. Cho & M. T. Nakamura. (2008). Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. Biochimica et Biophysica Acta, 1782(5), 341-348. DOI: 10.1016/j.bbadis.2008.02.007
  31. H. Yamashita, M. Takenoshita, M. Sakurai, R. K. Bruick, W. J. Henzel, W. Shillinglaw, D. Arnot & K. Uyeda. (2001). A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proceedings of the National Academy of Science of United State of America, 98(16), 9116-9121. DOI: 10.1073/pnas.161284298
  32. L. Ma, L. N. Robinson & H. C. Towle. (2006). ChREBP*Mlx is the principal mediator of glucose-induced gene expression in the liver. The Journal of Biological Chemistry, 281(39), 28721-28730. DOI: 10.1074/jbc.M601576200
  33. H. A. Coller, C. Grandori, P. Tamayo, T. Colbert, E. S. Lander, R. N. Eisenman & T. R. Golub. (2000). Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proceedings of the National Academy of Science of United State of America, 97(7), 3260-3265. DOI: 10.1073/pnas.97.7.3260
  34. M. Munz, R. Zeidler & O. Gires. (2005). The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Cancer Lett, 225(1), 151-157. DOI: 10.1016/j.canlet.2004. 11.048