アミノ酸シグナルに応答した肝臓脂質蓄積の新機構の解明

[1] L. Chantranupong, R. L. Wolfson, and D. M. Sabatini, “Nutrient-Sensing Mechanisms across Evolution,” Cell, vol. 161, no. 1, pp. 67–83, 2015.

[2] P. Dourlen, A. Sujkowski, R. Wessells, and B. Mollereau, “Fatty acid transport proteins in disease: New insights from invertebrate models,” Prog. Lipid Res., vol. 60, pp. 30–40, 2015.

[3] H. H. M. R.M. Forbes, A.R. Cooper, “The composition of the adult human body as determined by chemical analysis,” J. Biol. Chem, vol. 203, pp. 359–366, 1953.

[4] O. Davidenko, N. Darcel, G. Fromentin, and D. Tomé, “Control of protein and energy intake - brain mechanisms,” Eur. J. Clin. Nutr., vol. 67, no. 5, pp. 455–461, 2013.

[5] C. D. Morrison and T. Laeger, “Protein-dependent regulation of feeding and metabolism,” Trends Endocrinol. Metab., vol. 26, no. 5, pp. 256–262, 2015.

[6] 高橋伸一郎、竹中麻子、豊島由香、木村久美、加藤久典、福嶋俊明、山中大介、笹野史彦、南史朗、岩下光利, “発達と成長を司るホルモン，インスリン様成長因子,” 日本未熟児新生児学会雑誌, vol. 22, no. 1, pp. 19–25, 2010.

[7] C. Postic, R. Dentin, and J. Girard, “Role of the liver in the control of carbohydrate and lipid homeostasis,” Diabetes Metab., vol. 30, no. 5, pp. 398–408, 2004.

[8] M. Stumvoll, B. J. Goldstein, and T. W. Van Haeften, “Type 2 diabetes: principles of pathogenesis and therapy,” Lancet, vol. 365, pp. 1333–1346, 2005.

[9] Y. Izumida, N. Yahagi, Y. Takeuchi, M. Nishi, A. Shikama, A. Takarada, Y. Masuda, M. Kubota, T. Matsuzaka, Y. Nakagawa, Y. Iizuka, K. Itaka, K. Kataoka, S. Shioda, A. Niijima, T. Yamada, H. Katagiri, R. Nagai, N. Yamada, T. Kadowaki, and H. Shimano, “Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization.,” Nat. Commun., vol. 4, p. 2316, 2013.

[10] F. A. Lívero and A. Acco, “Molecular basis of alcoholic fatty liver disease: From incidence to treatment,” Hepatol. Res., 2015.

[11] M. Hernandez-Rodas, R. Valenzuela, and L. Videla, “Relevant Aspects of Nutritional and Dietary Interventions in Non-Alcoholic Fatty Liver Disease,” Int. J. Mol. Sci., vol. 16, no. 10, pp. 25168–25198, 2015.

[12] J. H. Lee, S. Friso, and S.-W. Choi, “Epigenetic mechanisms underlying the link between non-alcoholic fatty liver diseases and nutrition.,” Nutrients, vol. 6, no. 8, pp. 3303–3325, 2014.

[13] “Fatty liver in kwashiorkor,” Nutr. Rev., vol. 27, no. 9, pp. 261–263, 1969.

[14] S.-I. Takahashi, A. Takenaka, and T. Noguchi, “動物の成長を司るホルモン、インスリン様成長因子I,” 蛋白質 核酸 酵素, vol. 41, no. 3, pp. 267–280, 1996.

[15] H. H. Schmidt, T. D. Warner, K. Ishii, H. Sheng, and F. Murad, “Insulin secretion from pancreatic B cells caused by L-arginine-derived nitrogen oxides.,” Science, vol. 255, no. 5045, pp. 721–723, 1992.

[16] G. Gheni, M. Ogura, M. Iwasaki, N. Yokoi, K. Minami, Y. Nakayama, K. Harada, B. Hastoy, X. Wu, H. Takahashi, K. Kimura, T. Matsubara, R. Hoshikawa, N. Hatano, K. Sugawara, T. Shibasaki, N. Inagaki, T. Bamba, A. Mizoguchi, E. Fukusaki, P. Rorsman, and S. Seino, “Glutamate Acts as a Key Signal Linking Glucose Metabolism to Incretin/cAMP Action to Amplify Insulin Secretion,” Cell Rep., vol. 9, no. 2, pp. 661–673, 2014.

[17] J. A. Milner, “Mechanism for fatty liver induction in rats fed arginine deficient diets.,” J. Nutr., vol. 109, pp. 24–31, 1979.

[18] Y. Aoyama, H. Yasui, and K. Ashida, “Effect of dietary protein and amino acids in a choline-deficient diet on lipid accumulation in rat liver.,” J. Nutr., vol. 101, no. 6, pp. 739–45, 1971.

[19] K. Kimura, Y. Nakamura, Y. Inaba, M. Matsumoto, Y. Kido, S. I. Asahara, T. Matsuda, H. Watanabe, A. Maeda, F. Inagaki, C. Mukai, K. Takeda, S. Akira, T. Ota, H. Nakabayashi, S. Kaneko, M. Kasuga, and H. Inoue, “Histidine augments the suppression of hepatic glucose production by central insulin action,” Diabetes, vol. 62, no. 7, pp. 2266–2277, 2013.

[20] M. Katsumata, “Promotion of intramuscular fat accumulation in porcine muscle by nutritional regulation.,” Anim. Sci. J., vol. 82, no. 1, pp. 17–25, 2011.

[21] H. Nishi, D. Yamanaka, H. Kamei, Y. Goda, M. Kumano, Y. Toyoshima, A. Takenaka, M. Masuda, Y. Nakabayashi, R. Shioya, N. Kataoka, F. Hakuno, and S.-I. Takahashi, “Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition,” Sci. Rep., vol. 8, no. 5461, pp. 1–11, 2018.

[22] A. González and M. N. Hall, “Nutrient sensing and TOR signaling in yeast and mammals,” EMBO J., vol. 36, no. 4, pp. 397–408, 2017.

[23] K. Asano, “Translational and transcriptional control by eIF2 phosphorylation : requirement for integrity of ribosomal preinitiation complex,” Tampaku Kakusan Koso, vol. 51, no. 5, pp. 389–398, 2006.

[24] M. S. Kilberg, J. Shan, and N. Su, “ATF4-dependent transcription mediates signaling of amino acid limitation,” Trends Endocrinol. Metab., vol. 20, no. 9, pp. 436–443, 2009.

[25] K. Huang and D. C. Fingar, “Growing knowledge of the mTOR signaling network,” Semin. Cell Dev. Biol., vol. 36, pp. 79–90, 2014.

[26] R. L. Wolfson, L. Chantranupong, R. A. Saxton, K. Shen, S. M. Scaria, J. R. Cantor, and D. M. Sabatini, “Sestrin2 is a leucine sensor for the mTORC1 pathway,” Science (80-. )., vol. 351, no. 6268, pp. 43–8, 2015.

[27] L. Chantranupong, S. M. Scaria, R. A. Saxton, M. P. Gygi, K. Shen, G. A. Wyant, T. Wang, J. W. Harper, S. P. Gygi, and D. M. Sabatini, “The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway,” Cell, vol. 165, no. 1, pp. 153–164, 2016.

[28] X. Gu, J. M. Orozco, R. A. Saxton, K. J. Condon, G. Y. Liu, P. A. Krawczyk, S. M. Scaria, J. W. Harper, S. P. Gygi, and D. M. Sabatini, “SAMTOR is an S - adenosylmethionine sensor for the mTORC1 pathway,” Science (80-. )., vol. 358, no. 6364, pp. 813–818, 2017.

[29] R. Geiger, J. C. Rieckmann, T. Wolf, N. Zamboni, F. Sallusto, A. Lanzavecchia, R. Geiger, J. C. Rieckmann, T. Wolf, C. Basso, Y. Feng, T. Fuhrer, and M. Kogadeeva, “L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity Article L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity,” Cell, vol. 167, no. 3, pp. 1–14, 2016.

[30] S. Wang, Z. Tsun, R. Wolfson, K. Shen, G. Wyant, M. Plovanich, E. Yuan, T. Jones, L. Chantranupong, W. Comb, T. Wang, L. Bar-Peled, R. Zoncu, C. Straub, C. Kim, J. Park, B. Sabatini, and D. Sabatini, “Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1,” Science (80-. )., vol. 347, no. 6218, pp. 188– 194, 2015.

[31] P. M. Taylor, “Role of amino acid transporters in amino acid sensing,” Am. J. Clin. Nutr., vol. 99, no. 1, p. 223S–230S, 2014.

[32] T. Kohonen, “Self-organized formation of topologically correct feature maps,” Biol. Cybern., vol. 43, no. 1, pp. 59–69, 1982.

[33] D. E. Rumelhart, G. E. Hinton, and R. J. Williams, “Learning representations by back-propagating errors,” Nature, vol. 323, no. 6088, pp. 533–536, 1986.

[34] A. Takenaka, M. Mori, S. Yamada, J. Ohgane, S. Takahashi, and T. Noguchi, “Nutritional regulation of gene expression of insulin-like growth factor-binding proteins and the acid-labile subunit in various tissues of rats,” J Endocrinol, vol. 150, no. 1, pp. 33–41, 1996.

[35] Y. Toyoshima, R. Tokita, Y. Taguchi, N. Akiyama-akanishi, and A. Takenaka, “Tissue-specific effects of protein malnutrition on insulin signaling pathway and lipid accumulation in growing rats,” Endocr. J., vol. 61, no. 5, pp. 499–512, 2014.

[36] Y. Ozaki, T. Takeda, N. Akanishi, F. Hakuno, Y. Toyoshima, S.-I. Takahashi, and A. Takenaka, “Insulin injection restored increased insulin receptor substrate (IRS)-2 protein during short-term protein restriction but did not affect reduced insulin-like growth factor (IGF)-I mRNA or increased triglyceride accumulation in the liver of rats.,” Biosci. Biotechnol. Biochem., vol. 78, no. 1, pp. 130–8, 2014.

[37] S. G. Folch J, Lees M, “A simple method for the isolation and purification of total lipides from animal tissues.,” J. Biol. Chem., vol. 55, no. 3, pp. 999–1033, 1957.

[38] M. Masuda, Y. Nakabayashi, and G. Yagawa, “Radius Parallel Self-Organizing Map (RPSOM),” J. Comput. Sci. Technol., vol. 6, no. 1, pp. 16–27, 2012.

[39] J. Kasurinen, “A novel fluorescent fatty acid, 5-methyl-BDY-3-dodecanoic acid, is a potential probe in lipid transport studies by incorporating selectively to lipid classes of BHK cells,” Biochem. Biophys. Res. Commun., vol. 187, no. 3, pp. 1594–1601, 1992.

[40] K. Kolahi, S. Louey, O. Varlamov, and K. Thornburg, “Real-time tracking of BODIPY-C12 long-chain fatty acid in human term placenta reveals unique lipid dynamics in cytotrophoblast cells,” PLoS One, vol. 11, no. 4, pp. 1–23, 2016.

[41] J. Borensztajn, M. S. Rone, and T. J. Kotlar, “The inhibition in vivo of lipoprotein lipase (clearing-factor lipase) activity by triton WR-1339.,” Biochem. J., vol. 156, no. 3, pp. 539–543, 1976.

[42] S. Dash, C. Xiao, C. Morgantini, and G. F. Lewis, “New Insights into the Regulation of Chylomicron Production,” Annu. Rev. Nutr., vol. 35, no. 1, pp. 265–294, 2015.

[43] V. L. Malloy, C. E. Perrone, D. A. L. Mattocks, G. P. Ables, N. S. Caliendo, D. S. Orentreich, and N. Orentreich, “Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice,” Metabolism, vol. 62, no. 11, pp. 1651–1661, 2013.

[44] Y. Aoyama, A. Yoshida, and K. Ashida, “Effect of Some Dietary Additions to Either an Arginine- Devoid Diet or a Diet Supplemented with Orotic Acid Refed after Starvation on Liver Lipid Content during Essential Fatty Acid Deficiency in Rats,” J. Nutr., vol. 111, pp. 895–906, 1981.

[45] Y. Toyoshima, R. Tokita, Y. Ohne, F. Hakuno, T. Noguchi, S. Minami, H. Kato, and S. I. Takahashi, “Dietary protein deprivation upregulates insulin signaling and inhibits gluconeogenesis in rat liver,” J. Mol. Endocrinol., vol. 45, no. 5, pp. 329–340, 2010.

[46] Nutrient Requirements of Laboratory Animals; Fourth Revised Edition. 1995.

[47] D. M. Sabatini, “Twenty-five years of mTOR: Uncovering the link from nutrients to growth,” Proc. Natl. Acad. Sci., vol. 114, no. 45, pp. 11818–11825, 2017.

[48] I. Ben-Sahra, G. Hoxhaj, S. J. H. Ricoult, J. M. Asara, and B. D. Manning, “mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle,” Science (80-. )., vol. 351, no. 6274, pp. 728–733, 2016.

[49] I. Ben-Sahra, J. J. Howell, J. M. Asara, and B. D. Manning, “Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through mTOR and S6K1,” Science (80-. )., vol. 339, no. March, pp. 1323–1328, 2013.

[50] P. Nguyen, V. Leray, M. Diez, S. Serisier, J. Le Bloc’H, B. Siliart, and H. Dumon, “Liver lipid metabolism,” J. Anim. Physiol. Anim. Nutr. (Berl)., vol. 92, no. 3, pp. 272–283, 2008.

[51] J. Ha, S. Daniel, S. S. Broyles, and K. H. Kim, “Critical phosphorylation sites for acetyl-CoA carboxylase activity,” J. Biol. Chem., vol. 269, no. 35, pp. 22162–22168, 1994.

[52] X. Di He, W. Gong, J. N. Zhang, J. Nie, C. F. Yao, F. S. Guo, Y. Lin, X. H. Wu, F. Li, J. Li, W. C. Sun, E. D. Wang, Y. P. An, H. R. Tang, G. Q. Yan, P. Y. Yang, Y. Wei, Y. Z. Mao, P. C. Lin, J. Y. Zhao, Y. Xu, W. Xu, and S. M. Zhao, “Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations,” Cell Metab., vol. 27, no. 1, p. 151–166.e6, 2017.

[53] A. J. Meijer and P. Codogno, “Regulation and role of autophagy in mammalian cells,” Int. J. Biochem. Cell Biol., vol. 36, no. 12, pp. 2445–2462, 2004.

[54] N. Mizushima, A. Yamamoto, M. Matsui, T. Yoshimori, and Y. Ohsumi, “In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker,” Mol. Biol. Cell, vol. 15, no. 3, pp. 1101–1111, 2004.

[55] Ö. H. Yilmaz, P. Katajisto, D. W. Lamming, Y. Gültekin, K. E. Bauer-Rowe, S. Sengupta, K. Birsoy, A. Dursun, V. Onur Yilmaz, M. Selig, G. P. Nielsen, M. Mino- Kenudson, L. R. Zukerberg, A. K. Bhan, V. Deshpande, and D. M. Sabatini, “MTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake,” Nature, vol. 486, no. 7404, pp. 490–495, 2012.

[56] M. Igarashi and L. Guarente, “mTORC1 and SIRT1 Cooperate to Foster Expansion of Gut Adult Stem Cells during Calorie Restriction,” Cell, vol. 166, no. 2, pp. 436– 450, 2016.

[57] N. Emmanuel, S. Ragunathan, Q. Shan, F. Wang, A. Giannakou, N. Huser, G. Jin, J. Myers, R. T. Abraham, and K. Unsal-Kacmaz, “Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase,” Cell Rep., vol. 19, no. 13, pp. 2665–2680, 2017.

[58] J. A. Milner, “Metabolic aberrations associated with arginine deficiency,” J. Nutr., vol. 115, no. 4, pp. 516–523, 1985.

[59] J. S. Lee, L. Adler, H. Karathia, N. Carmel, S. Rabinovich, N. Auslander, R. Keshet, N. Stettner, A. Silberman, L. Agemy, D. Helbling, R. Eilam, Q. Sun, A. Brandis, S. Malitsky, M. Itkin, H. Weiss, S. Pinto, S. Kalaora, R. Levy, E. Barnea, A. Admon, D. Dimmock, N. Stern-Ginossar, A. Scherz, S. C. S. Nagamani, M. Unda, D. M. Wilson, R. Elhasid, A. Carracedo, Y. Samuels, S. Hannenhalli, E. Ruppin, and A. Erez, “Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures,” Cell, vol. 174, no. 6, p. 1559–1570.e22, 2018.

[60] J. D. Young, “The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30-year collaborative odyssey,” Biochem. Soc. Trans., vol. 44, no. 3, pp. 869–876, 2016.

[61] J. Furukawa, K. Inoue, J. Maeda, T. Yasujima, K. Ohta, Y. Kanai, T. Takada, H. Matsuo, and H. Yuasa, “Functional identification of SLC43A3 as an equilibrative nucleobase transporter involved in purine salvage in mammals,” Sci. Rep., vol. 5, no. October, pp. 1–11, 2015.

[62] Y. Deng, Z. V Wang, R. Gordillo, Y. An, C. Zhang, Q. Liang, J. Yoshino, K. M. Cautivo, J. De Brabander, J. K. Elmquist, J. D. Horton, J. A. Hill, S. Klein, and P. E. Scherer, “An adipo-biliary-uridine axis that regulates energy homeostasis,” Science (80-. )., vol. 355, no. eaaf5375, 2017.

[63] P. Nicklin, P. Bergman, B. Zhang, E. Triantafellow, H. Wang, B. Nyfeler, H. Yang, M. Hild, C. Kung, C. Wilson, V. E. Myer, J. P. MacKeigan, J. a. Porter, Y. K. Wang, L. C. Cantley, P. M. Finan, and L. O. Murphy, “Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy,” Cell, vol. 136, no. 3, pp. 521–534, 2009.

[64] D. C. I. Goberdhan, C. Wilson, and A. L. Harris, “Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot,” Cell Metab., vol. 23, no. 4, pp. 580–589, 2016.

[65] K. Sumita, Y. H. Lo, K. Takeuchi, M. Senda, S. Kofuji, Y. Ikeda, J. Terakawa, M. Sasaki, H. Yoshino, N. Majd, Y. Zheng, E. R. Kahoud, T. Yokota, B. M. Emerling, J. M. Asara, T. Ishida, J. W. Locasale, T. Daikoku, D. Anastasiou, T. Senda, and A. T. Sasaki, “The Lipid Kinase PI5P4Kβ Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis,” Mol. Cell, vol. 61, no. 2, pp. 187–198, 2016.

[66] F. Pietrocola, L. Galluzzi, J. M. Bravo-San Pedro, F. Madeo, and G. Kroemer, “Acetyl coenzyme A: A central metabolite and second messenger,” Cell Metab., vol. 21, no. 6, pp. 805–821, 2015.

[67] S. J. Mentch and J. W. Locasale, “One‐carbon metabolism and epigenetics: understanding the specificity,” Ann. N. Y. Acad. Sci., pp. 1–8, 2015.

[68] Z. Zhang, M. Tan, Z. Xie, L. Dai, Y. Chen, and Y. Zhao, “Identification of lysine succinylation as a new post-translational modification,” Nat. Chem. Biol., vol. 7, no. 1, pp. 58–63, 2011.

[69] I. P. Pogribny, V. P. Tryndyak, T. V. Bagnyukova, S. Melnyk, B. Montgomery, S. a. Ross, J. R. Latendresse, I. Rusyn, and F. a. Beland, “Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet,” J. Hepatol., vol. 51, no. 1, pp. 176–186, 2009.

[70] F. Obata, K. Tsuda-Sakurai, T. Yamazaki, R. Nishio, K. Nishimura, M. Kimura, M. Funakoshi, and M. Miura, “Nutritional Control of Stem Cell Division through S- Adenosylmethionine in Drosophila Intestine,” Dev. Cell, vol. 44, no. 6, p. 741–751.e3, 2018.

[71] J. H. Sang and R. C. King, “Nutritional requirements of axenically cultured Drosophila melanogaster adults,” J. Exp. Biol., vol. 38, no. 4, pp. 793–809, 1961.

[72] R. Weindruch and R. S. Sohal, “Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging.,” N. Engl. J. Med., vol. 337, no. 14, pp. 986–994, 1997.

[73] R. A. Miller, G. Buehner, Y. Chang, J. M. Harper, R. Sigler, and M. Smith-Wheelock, “Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance,” Aging Cell, vol. 4, no. 3, pp. 119–125, 2005.

[74] P. Kapahi, M. Kaeberlein, and M. Hansen, “Dietary restriction and lifespan: Lessons from invertebrate models,” Ageing Res. Rev., vol. 39, pp. 3–14, 2017.

[75] S. Post and M. Tatar, “Nutritional geometric profiles of insulin/IGF expression in Drosophila melanogaster,” PLoS One, vol. 11, no. 5, pp. 1–16, 2016.

[76] N. Agrawal, R. Delanoue, A. Mauri, D. Basco, M. Pasco, B. Thorens, and P. L??opold, “The Drosophila TNF Eiger Is an Adipokine that Acts on Insulin-Producing Cells to Mediate Nutrient Response,” Cell Metab., vol. 23, no. 4, pp. 675–684, 2016.

[77] D. A. Skorupa, A. Dervisefendic, J. Zwiener, and S. D. Pletcher, “Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster,” Aging Cell, vol. 7, no. 4, pp. 478–490, 2008.

[78] Y. Taya, Y. Ota, A. C. Wilkinson, K. Ayano, H. Watarai, M. Kasai, H. Nakauchi, and S. Yamazaki, “Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation,” Science (80-. )., vol. 354, no. 6316, pp. 1152–1155, 2016.

[79] N. Shiraki, Y. Shiraki, T. Tsuyama, F. Obata, M. Miura, G. Nagae, H. Aburatani, K. Kume, F. Endo, and S. Kume, “Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells,” Cell Metab., vol. 19, no. 5, pp. 780– 794, 2014.

[80] J. Zhang, N. N. Pavlova, and C. B. Thompson, “Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine,” EMBO J., vol. 36, no. 10, pp. 1302– 1315, 2017.

[81] N. N. Pavlova, S. Hui, J. M. Ghergurovich, J. Fan, A. M. Intlekofer, R. M. White, J. D. Rabinowitz, C. B. Thompson, and J. Zhang, “As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino Acid,” Cell Metab., vol. 27, pp. 1– 11, 2018.

[82] J. Alba-Roth, O. A. Müller, J. Schopohl, and K. Von Werder, “Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion,” J. Clin. Endocrinol. Metab., vol. 67, no. 6, pp. 1186–1189, 1988.

[83] V. W.-S. Wong, L. A. Adams, V. de Lédinghen, G. L.-H. Wong, and S. Sookoian, “Noninvasive biomarkers in NAFLD and NASH — current progress and future promise,” Nat. Rev. Gastroenterol. Hepatol., vol. 15, no. 8, pp. 461–478, 2018.

[84] H. Sano, A. Nakamura, M. J. Texada, J. W. Truman, H. Ishimoto, A. Kamikouchi, Y. Nibu, K. Kume, T. Ida, and M. Kojima, “The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster,” PLoS Genet., vol. 11, no. 5, pp. 1–26, 2015.

[85] R. Delanoue, E. Meschi, N. Agrawal, A. Mauri, Y. Tsatskis, H. McNeill, and P. Léopold, “Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor,” Science (80-. )., vol. 353, no. 6307, pp. 1553–1556, 2016.

[86] A. Rajan and N. Perrimon, “Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion,” Cell, vol. 151, no. 1, pp. 123– 137, 2012.