15K00827 研究成果報告書

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(TG) TG sterol regulatory element- binding protein (SREBP)-1c (Diabetes 53:560-569, 2004) SREBP-1c (1) SREBP-1c SREBP-1c liver X receptor (LXR)LXR O-Glc NAc (O-linked -N-acetyl glucosamine) (J Biol Chem 285:1607-1615, 2010) O-GlcNAc UDP-GlcNAc 6- (F6P) F6P LXR O-GlcNAc 2 F6P 2 SREBP-1c fatty acid elongase-6 (Elovl6) stearoyl-coa desaturase(scd) 1 (Nat Med 13:1193-202, 2007, Diabetes 62:561-71, 2013) LC/MS 3

1F6P : 20%8 SREBP-1c LXR O-GlcNAc GPD1(Glycerol-3-phosphate dehydrogenase1) GPD1 DHAP -3-Gro3PGro3P DHAP GPD1 BALBc/HeA 3- TG (Biochem Biophys Res Commun, 444, 525 (2014)) 2 LC-MS : 78 BDHQ brief-type self-administered diet history questionnaire PPAR 1F6P mrna Insulin Glycogen mrna 4 mrna LXR O-GlcNAc UDP-GlcNAc 5 LXRO-GlcNAcUDP-GlcNAc UDP-GlcNAc STZ Insulin Glycogen mrna STZmRNA GPD1 GPD1 NAD + GPD1 NAD + GPD1 GPD1 GPD1 AMP-activated protein kinase ( AMPK) GPD1 GPD1

GPD1 GPD1 DHAP GPD1 GPD1 () 2 4-8 24 Phosphatidylcholine (PC) sn-1 sn-2 PC PC PC PC PC PC(16:0/16:1)PC(16:0/18:1) PC PC sn-1 16:0 sn-2 16:1 18:1 ( ) : 78 PC PC(16:0/16:1)PC(16:0/18:1) () 8 PC SCD1 16:1 18:1 LPCAT4 16:1-CoA 18:1-CoA Lyso-PC (16:0) PC (16:0/16:1) PC (16:0/18:1) () PC (16:0/18:1) PPAR PC PC (16:0/18:1) PC (16:0/16:1)PPAR () F6P LXR O-GlcNAc GPD1 DHAP GPD1 sn-1 16:0 sn-2 16:1 18:1 PC(16:0/16:1)PC(16:0/18:1) SCD1 LCAT4 ACC FAS SCD1 De novo lipogenesis Δ9 desaturation High carbohydrate diet Fatty acid (16:0) (16:1) (18:1) PC synthesis PC(16:0/16:1) PC(16:0/18:1) PC 7 PC PC(16:0/16:1)PC(16:0/18:1) PC(16:0/16:1)PC(16:0/18:1) PC(16:0/16:1)PC(16:0/18:1) PPAR

71 Inoue, M., Senoo, N., Sato, T., Nishimura, Y., Nakagawa, T., Miyoshi, N., Goda, T., Morita, A., and Miura, S., Effects of the dietary carbohydrate-fat ratio on plasma phosphatidylcholine profiles in human and mouse. J Nutr Biochem, 50, 83-94 (2017). Sato, T., Yoshida, Y., Morita, A., Mori, N., and Miura, S., Glycerol-3-phosphate dehydrogenase 1 deficiency induces compensatory amino acid metabolism during fasting in mice. Metabolism, 65, 1646-1656 (2016). Senoo, N., Miyoshi, N., Goto-Inoue, N., Minami, K., Yoshimura, R., Morita, A., Sawada, N., Matsuda, J., Ogawa, Y., Setou, 201611 58 20166 70 20165 70 M., Kamei, Y., and Miura, S.: 20165 PGC-1α-mediated changes in phospholipid profiles of exercise-trained skeletal muscle. J Lipid Res, 56, 2286-2296 (2015). Sato, T., Morita, A., Mori, N., and Miura, S.: Glycerol-3-phosphate dehydrogenase 1 69 201511 Glycerol 3-phosphate dehydrogenase 1 deficiency enhances exercise capacity due to increased lipid oxidation during strenuous exercise. Biochem Biophys Res Commun, 457, 653-658 (2015). Sato, T., Morita, A., Mori, N., and Miura, S.: The roles of GPD1 in exercise capacity. Oral session16 Nutritional biochemistry, The 12th Asian Congress of Nutrition. 2015 5 PGC-1α 23 (2), 67-71 (2017). phosphatidylcholine, 59, 51-53 (2017). Miura, S., Inoue, M., Senoo, N., Sato, T., Nishimura, Y., Nakagawa, T., Miyoshi, N., Goda, T., and Morita, A., Effects of the dietary carbohydrate-fat ratio on plasma phosphatidylcholine profiles in human and mouse., Gordon Research Conference, Lipids, Molecular & Cellular Biology of, 2017730-4Waterville valley, NH, USA Sato, T., Yoshida, Y., Morita, A., Mori, N., and Miura, S., Glycerol-3-phosphate dehydrogenase 1 deficiency induces, 58, compensatory amino acid metabolism during 51-52 (2016). fasting in mice., 12 th China-Japan Symposium on Health Sciences, 20172 Hangzhou, China phosphatidylcholine 59 20176 15-16 Glycerol-3-phosphate dehydrogenase 1 71 201611 71 20175 19-21 Glycerol-3-phosphate dehydrogenase 1 71 2017519-21

Sato, T., Yoshida, Y., Morita, A., Mori, N., and Miura, S., Glycerol-3-phosphate dehydrogenase 1 deficiency induces compensatory amino acid metabolism during fasting in mice., The 21st Shizuoka Forum on Health and Longevity, 201611 Shizuoka Inoue, M., Sato, T., Senoo, N., Nishimura, Y., Miyoshi, N., Goda, T., Morita, A., and Miura, S., Long-term effects of carbohydrate/fat ratio in the diet on plasma phospholipid composition in mice and human., The 21st Shizuoka Forum on Health and Longevity, 201611 Shizuoka Sato, T., Morita, A., Mori, N., and Miura, S., The roles of GPD1 in maintaining blood glucose levels under fasting conditions., Experimental Biology 2016, 2016 4 San Diego Sato, T., Morita, A., Mori, N., and Miura, S.: The roles of GPD1 in maintaining blood glucose levels under fasting conditions. The 20th Shizuoka Forum on Health and Longevity, 201510 Sato, T., Morita, A., Mori, N., and Miura, S.: Glycerol 3-phosphate dehydrogenase 1 deficiency enhances exercise capacity due to increased lipid oxidation during strenuous exercise. Cell Symposia: Exercise Metabolism, 20157 Amsterdam Nishimura, Y., Sato, T., Inoue, M., Miura, S., and Morita, A.: Mechanisms of lipogenic gene expression in postprandial liver. Poster session 01 Nutritional biochemistry 1, The 12th Asian Congress of Nutrition. 20155 Inoue, M., Sato, T., Senoo, N., Miyoshi, N., Goda, T., Morita, A., and Miura, S., Long-term effects of carbohydrate/fat ratio in the diet on plasma phospholipid composition in mice and human., 12 th China-Japan Symposium on Health Sciences, 20172Hangzhou, China GPD1 2015 201512 2015 201512 2015 201512