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1 H., Hoshino, K., Kaisho, T., Kuwata, H., Takeushi, O., Takeshige,K.,Saitoh,T.,Yamaoka,S.,Yamamoto,N.,Yamamoto, S., Muta, T., Takeda, K., & Akira, S.Nature,,. Yamazaki, S., Muta, T., Matsuo, S., & Takeshige, K.J. Biol. Chem.,,. Motoyama, M., Yamazaki, S., Eto-Kimura, A., Takeshige, K., &Muta,T.J. Biol. Chem.,,. Matsuo, S., Yamazaki, S., Takeshige, K., & Muta, T. Biochem. J.,,. Kayama, H., Ramirez-Carrozzi, V.R., Yamamoto, M., Mizutani, T., Kuwata, H., Iba, H., Matsumoto, M., Honda, K., Smale, S. T., & Takeda, K.J. Biol. Chem.,,. Kontoyiannis, D., Pasparakis, M., Pizarro, T.T., Cominelli, F., & Kollias, G.Immunity,,. Cheng, J.D., Ryseck, R-P., Attar, R.M., Dambach, D., & Bravo, R.J. Exp. Med.,,. Regulation of inflammatory genes by the nuclear protein IκB-ζ Soh Yamazaki Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University,, Maidashi, Higashi-ku, Fukuoka, Japan Elovl- ER sterol regulatory element-binding protein SREBP - c SREBP- c SREBP- c feedback fatty acid synthase; FAS FAS n- n- Stearoyl-CoA desaturase SCD n- n- CoA ER FAS FAS Elovl- SREBP- a DNA SREBP SREBP- a

2 Elovl- Elovl- HXXHH C KKXX-like C n- fatty acyl-coa elongase Elovl- Elovl- FAS Elovl- SCD- Elovl- Elovl- SREBP Elovl- Elovl- SREBP- Elovl- SREBP- PUFA Elovl- PUFA Elovl- SREBP- Elovl- bp bp SREBP SRE SRE Elovl- SREBP Elovl- Elovl-SREBP Elovl- SREBP- Elovl-

3 Elovl- A B C Elovl- Elovl- Elovl- Elovl- Elovl- de novo Elovl- n- n- Elovl- Elovl- A B Elovl- Elovl- Elovl- Elovl- Elovl- C Elovl- Elovl- Akt Akt Elovl- Akt A Elovl-

4 Elovl- A B Elovl- Akt Elovl- Elovl- Elovl- Elovl- Elovl- B SREBP- FAS SCD- Elovl- SCD- peroxisome proliferators activated receptor PPAR α acyl-coa oxidase AOX β Elovl- Elovl- IRS- Elovl- Elovl- IRS- SREBP-

5 Elovl-6 Elovl-6 Elovl-6 Elovl- SREBP- IRS- SRE IRS- Elovl- SREBP- IRS- IRS- Akt protein kinase C PKC ε diacylglycerol DAG PKCε Elovl- Elovl- Elovl- Elovl- Elovl- KO

6 ACC FAS SCD Elovl- NASH Matsuzaka, T., Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yamamoto, T., Inoue, N., Ishikawa, M., Okada, S., Ishigaki, N., Iwasaki, H., Iwasaki, Y., Karasawa, T., Kumadaki, S., Matsui, T., Sekiya, M., Ohashi, K., Hasty, A.H., Nakagawa, Y., Takahashi, A., Suzuki, H., Yatoh, S., Sone, H., Toyoshima, H., Osuga, J., & Yamada, N.Nat. Med.,,. Shimano, H., Yahagi, N., Amemiya-Kudo, M., Hasty, A.H., Osuga, J., Tamura, Y., Shionoiri, F., Iizuka, Y., Ohashi, K., Harada, K., Gotoda, T., Ishibashi, S., & Yamada, N.J. Biol. Chem.,,. Shimano, H.Prog. Lipid Res.,,. Shimano, H.J. Mol. Med.,,. Ide, T., Shimano, H., Yahagi, N., Matsuzaka, T., Nakakuki, M., Yamamoto, T., Nakagawa, Y., Takahashi, A., Suzuki, H., Sone, H., Toyoshima, H., Fukamizu, A., & Yamada, N. Nat. Cell Biol.,,. Yahagi, N., Shimano, H., Hasty, A.H., Matsuzaka, T., Ide, T., Yoshikawa, T., Amemiya-Kudo, M., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Osuga, J., Harada, K., Gotoda, T., Nagai, R., Ishibashi, S., & Yamada, N.J. Biol. Chem.,,. Takahashi, A., Motomura, K., Kato, T., Yoshikawa, T., Nakagawa, Y., Yahagi, N., Sone, H., Suzuki, H., Toyoshima, H., Yamada, N., & Shimano, H.Diabetes,,. Kato, T., Shimano, H., Yamamoto, T., Yokoo, T., Endo, Y., Ishikawa, M., Matsuzaka, T., Nakagawa, Y., Kumadaki, S., Yahagi, N., Takahashi, A., Sone, H., Suzuki, H., Toyoshima, H., Hasty, A.H., Takahashi, S., Gomi, H., Izumi, T., & Yamada, N.Cell Metab., :. Yahagi, N., Shimano, H., Hasty, A.H., Amemiya-Kudo, M., Okazaki, H., Tamura, Y., Iizuka, Y., Shionoiri, F., Ohashi, K., Osuga, J., Harada, K., Gotoda, T., Nagai, R., Ishibashi, S., & Yamada, N.J. Biol. Chem.,,. Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakakuki, M., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Nagai, R., Osuga, J., Yamada, N., & Shimano, H.,Hepatology,,. Matsuzaka, T., Shimano, H., Yahagi, N., Yoshikawa, T., Amemiya-Kudo, M., Hasty, A.H., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Osuga, J., Takahashi, A., Yato, S., Sone, H., Ishibashi, S., & Yamada, N.J. Lipid Res.,,. Moon, Y.A., Shah, N.A., Mohapatra, S., Warrington, J.A., & Horton, J.D.J. Biol. Chem.,,. Nagarajan, R., Le, N., Mahoney, H., Araki, T., & Milbrandt, J. Proc. Natl. Acad. Sci. USA.,,. Kumadaki, S., Matsuzaka, T., Kato, T., Yahagi, N., Yamamoto, T., Okada, S., Kobayashi, K., Takahashi, A., Yatoh, S., Suzuki, H., Yamada, N., & Shimano, H.Biochem. Biophys. Res. Com.,,. Bruce, C.R. & Febbraio, M.A.Nat. Med.,,. Quality aspect of lipid accumulation in insulin resistance A lesson from long fatty acid elongase, Elovl- Hitoshi Shimano Department of Internal Medicine Endocrinology and Metabolism, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tennodai, Tsukuba-City, Ibaraki -, Japan

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