根據流行病學調查，全球肥胖人口日益增多，而肥胖與許多疾病之發生相關。肥胖會影響血糖、血脂與血壓等變化，長期會造成血液生化值異常及胰島素阻抗等現象，為代謝症候群之危險因子。種子胜肽lunasin經研究證實具有抗腫瘤、抗發炎、抗氧化及降膽固醇等生理功能。本研究目的為探討lunasin處裡對飲食誘發肥胖C57BL/6J公鼠之血液生化值、血清與肝臟小分子代謝體的影響；及對C2C12小鼠骨骼肌細胞葡萄糖代謝與胰島素敏感性之影響。第一部分動物實驗共分低脂飲食組 (low fat diet, LF)、高脂飲食組 (high fat diet, HF)、高脂飲食加腹腔注射4及20 mg/kg bw/day lunasin組 (HF+low dose lunasin, HF-LL及HF+high dose lunasin, HF-HL)以及高脂飲食添加富含lunasin之大豆蛋白組 (HF+ lunasin dietary intake, HF-DL)。結果發現，HF-HL組及HF-DL組顯著減緩肥胖小鼠葡萄糖耐受性異常之情形，且HF-HL組有降低血清三酸甘油酯之趨勢。然而lunasin處理對小鼠血糖、胰島素、血脂及肝臟脂質過氧化物則無顯著影響。另外，血液與肝臟小分子代謝體分析結果，HF組相較於LF組，克式循環和糖解作用中間產物及嘌呤代謝終產物uric acid顯著增加，且膽酸合成及膽固醇代謝相關及參與胺基酸代謝等小分子顯著下降。而lunasin處理能調節肥胖小鼠肝臟TCA cycle和糖解作用之中間產物及uric acid異常增加之情形，亦可改善肥胖小鼠血清及肝臟中參與胺基酸代謝之小分子下降之現象。第二部分細胞實驗探討lunasin介入對C2C12小鼠骨骼肌細胞之葡萄糖代謝，結果發現，lunasin處理能顯著增加C2C12細胞對葡萄糖之利用，但不影響到胰島素阻抗之表現。綜合上述，動物實驗中，HF-HL及HF-DL組可減緩肥胖小鼠葡萄糖耐受性異常推測可能經由調節血清與肝臟小分子代謝進而改善肥胖小鼠部分代謝異常情形。而飲食中添加富含lunasin的大豆蛋白對肥胖小鼠之影響不如腹腔注射lunasin純品效應強烈。而lunasin如何調控肥胖小鼠生理與對骨骼肌細胞葡萄糖代謝影響之相關路徑，值得進一步探討。

The worldwide prevalence of obesity has largely increase according to epidemiologic studies. Obesity is related to many diseases, such as metabolic syndrome, and causes physiological changes in blood sugar, blood lipids, blood pressure, metabolic disorders, and insulin resistance. Lunasin, a seed peptide, exerts many bioactive functions including cancer prevention, immune regulation, anti-oxidation and anti-cholesterol. The aim of this study is to investigate the effect of lunasin on serum biochemical analysis, and metabolic profiling of serum and liver in high-fat diet-induced obese C57BL/6J mice. Additionaly, C2C12 skeleton muscle cells were invesigated the effect of lunasin on glucose uptake and insulin sensitivity. In vivo, mice were divided to five groups and fed experimental diets, including low-fat diet (LF) or high-fat diet (HF), HF with intraperitoneal injected (IP) with 4 or 20 mg/kg bw/day synthetic lunasin (HF-LL, HF-HL), and supplemented lunasin of natural soy protein isolate in diet (20 mg/kg bw/day, HF-DL). The data has shown that high dose of lunasin IP and lunasin of natural soy protein isolate significantly improve glucose tolerance in obese mice. However, lunasin treatment didn’t affect serum levels of glucose, insulin, TG and cholesterol, and MDA formation in liver of mice. In the metabolic profiling, mice of HF group have shown that the metabolic intermediates of TCA cycle, glycolysis and uric acid were increased, and metabolites related to bile acid and amino acid were decrease compared to the LF group. Lunasin treatment modulated abnormally changes of those metabolites. In vitro, C2C12 cells were treated with synthetic lunasin and lunasin-enriched soy protein isolate. The data has showed that lunasin increased glucose uptake in C2C12 cells, but it doesn’t affect insulin resistance. In conclusion, our results demonstrated that high-dose IP of lunasin and lunasin dietary intake prevented glucose intolerance in obese mice. Lunasin treatment improving metabolic disorders in obese mice were found in metabolic profiling analysis. More research need to be carried out to know the mechanism of metabolic regulation in obese mice and the signaling pathway of glucose homeostasis in mice muscle cells.

一、中文文獻
臺灣衛生福利部國民健康署 (2018年6月15日)。106年國人死因統計結果。取自https://www.mohw.gov.tw/cp-16-41794-1.html
臺灣衛生福利部國民健康署 (2016年12月28日)。代謝症候群學習手冊。取自https://www.hpa.gov.tw/Pages/List.aspx?nodeid=1181
周美佳 (2016)。探討種子胜肽Lunasin對於肥胖引起的發炎模式之免疫調節作用。 國立臺灣師範大學，台北市。

二、英文文獻
Akhlaghi, M., Zare, M., & Nouripour, F. (2017). Effect of soy and soy isoflavones on obesity-related anthropometric measures: a systematic review and meta-analysis of randomized controlled clinical trials. Advances in Nutrition, 8(5), 705-717.
Andrikopoulos, S., Blair, A. R., Deluca, N., Fam, B. C., & Proietto, J. (2008). Evaluating the glucose tolerance test in mice. American journal of physiology. Endocrinology and Metabbolism, 295, E1323–E1332.
Ayala, J. E., Samuel, V. T., Morton, G. J., Obici, S., Croniger, C. M., Shulman, G. I., Wasserman, D. H., & McGuinness, O. P. (2010). Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Disease Models & Mechanisms, 3, 525-534.
Begriche, K., Massart, J., Robin, M. A., Bonnet, F., & Fromenty, B. (2013). Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology, 58(4), 1497-1507.
Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Glycolysis Is an Energy-Conversion Pathway in Many Organisms. Biochemistry (5th ed.): New York: W H Freeman.
Breum, L., Rasmussen, M. H., Hilsted, J., & Fernstrom, J. D. (2003). Twenty-four–hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. The American journal of clinical nutrition, 77(5), 1112-1118.
Cam, A., Sivaguru, M., & Mejia, E. G. d. (2013). Endocytic Mechanism of Internalization of Dietary Peptide Lunasin into Macrophages in Inflammatory Condition Associated with Cardiovascular Disease. PLoS ONE, 8(9), e72115.
Cavazos, A., Morales, E., Dia, V. P., & Mejia, E. G. d. (2012). Analysis of Lunasin in Commercial and Pilot Plant Produced Soybean Products and an Improved Method of Lunasin Purification. Journal of Food Science, 77.
Chang, H. C., Lewis, D., Tung, C. Y., Han, L., Henriquez, S. M. P., Voiles, L., Lupov I. P., Pelloso, D., Sinn, A. L., Pollok, K. E., Lumen, B. O. d., Li, F. Blum, J. S., Srivastava, S., & Robertson, M. J. (2014). Soypeptide lunasin in cytokine immunotherapy for lymphoma. Cancer Immunology Immunotherapy, 63(3), 283–295.
Chatterjee, C., Gleddie, S., & Xiao, C. W. (2018). Soybean bioactive peptides and their functional properties. Nutrients, 10(9), 1211.
Chaves Filho, A. J. M., Lima, C. N. C., Vasconcelos, S. M. M., Lucena, D. F. d., Maes, M., & Macedo, D. (2018). IDO chronic immune activation and tryptophan metabolic pathway: a potential pathophysiological link between depression and obesity. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 80, 234-249.
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017). Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology, 152(7), 1679-1694.
Chen, H. H., Tseng, Y. J., Wang, S. Y., Tsai, Y. S., Chang, C. S., Kuo, T. C., Yao, W. J., Shieh, C. C., & Kuo, P. H. (2015). The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity. International journal of obesity, 39(8), 1241.
Chong, J., Soufan, O., Li, C., Caraus, I., Li, S., Bourque, G., Wishart D. S., & Xia, J. (2018). MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic acids research, 46(W1), W486-W494.
Cirillo, P., Sato, W., Reungjui, S., Heinig, M., Gersch, M., Sautin, Y., Nakagawa, T., & Johnson, R. J. (2006). Uric acid, the metabolic syndrome, and renal disease. Journal of the American Society of Nephrology, 17(12 suppl 3), S165-S168.
Cruz-Huerta, E., Fernández-Tomé, S., Arques, M. C., Amigo, L., Recio, I., Clementeb, A., & Hernández-Ledesma, B. (2015). The protective role of the Bowman-Birk protease inhibitor in soybean lunasin digestion: the effect of released peptides on colon cancer growth. Food & Function, 6, 2626–2635.
Deng, Y., Wang, Z. V., Gordillo, R., An, Y., Zhang, C., Liang, Q., Yoshino, J., Cautivo, K. M., Brabander, J. D., Elmquist, J K., & Horton, J. D. (2017). An adipo-biliary-uridine axis that regulates energy homeostasis. Science, 355(6330), eaaf5375.
Deng, Y., Wang, Z. V., Gordillo, R., Zhu, Y., Ali, A., Zhang, C., Wang, X., Shao, M., Zhang, Z., Lyengar, R., & Gupta, R. K. (2018). Adipocyte Xbp1s overexpression drives uridine production and reduces obesity. Molecular metabolism, 11, 1-17.
Després, J.-P., & Lemieux, I. (2006). Abdominal Obesity and the Metabolic Syndrome. Nature, 444, 881–887.
Dia, V. P., & de Mejia, E. G. (2011). Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells. Molecular nutrition & food research, 55(4), 623-634.
Dobolyi, A., Juhasz, G., Kovacs, Z., & Kardos, J. (2011). Uridine Function in the Central Nervous System. Current Topics in Medicinal Chemistry, 11(8), 1058 - 1067.
Drori, A., Rotnemer-Golinkin, D., Zolotarov, L., & Ilan, Y. (2017). Oral Administration of CardioAid and Lunasin Alleviates Liver Damage in a High-Fat Diet Nonalcoholic Steatohepatitis Model. Digestion, 96, 110–118.
Dugani, C. B., & Klip, A. (2005). Glucose transporter 4: cycling, compartments and controversies. EMBO reports, 6(12), 1137-1142.
Eckel, R. H., Grundy, S. M., & Zimmet, P. Z. (2005). The metabolic syndrome. The lancet, 365(9468), 1415-1428.
Fang, P., Yu, M., Zhang, L., Wan, D., Shi, M., Zhu, Y., Bo, P., & Zhang, Z. (2017). Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway. Molecular and cellular endocrinology, 448, 77-86.
Favero, G., Stacchiotti, A., Castrezzati, S., Bonomini, F., Albanese, M., Rezzani, R., & Rodella, L. F. (2015). Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice. Nutrition Research, 35(10), 891-900.
Fernández-Tomé, S., Ramos, S., Cordero-Herrera, I., Recio, I., Goya, L., & Hernández-Ledesma, B. (2014). In vitro chemo-protective effect of bioactive peptide lunasin against oxidative stress in human HepG2 cells. Food Research International, 62, 793–800.
Fiehn, O. (2002). Metabolomics—the link between genotypes and phenotypes. Functional genomics, 155-171.
Fujita, Y., & Maki, K. (2015). High-fat diet-induced obesity triggers alveolar bone loss and spontaneous periodontal disease in growing mice. BMC obesity, 3(1), 1.
Gallou‐Kabani, C., Vigé, A., Gross, M. S., Rabès, J. P., Boileau, C., Larue‐Achagiotis, C., Tomé, D., Jais, J. P., & Junien, C. (2007). C57BL/6J and A/J mice fed a high‐fat diet delineate components of metabolic syndrome. Obesity, 15(8), 1996-2005.
Galvez, A. F. (2012). Abstract 10693: Identification of Lunasin as the Active Component in Soy Protein Responsible for Reducing LDL Cholesterol and Risk of Cardiovascular Disease. Circulation, 126.
Galvez, A. F., Chen, N., Macasieb, J., & Lumen, B. O. d. (2001). Chemopreventive Property of a Soybean Peptide (Lunasin) That Binds to Deacetylated Histones and Inhibits Acetylation. Canver Research, 61, 7473–7478.
Galvez, A. F., Revilleza, M. J. R., & De Lumen, B. O. (1997). A novel methionine-rich protein from soybean cotyledon: cloning and characterization of cDNA (accession no. AF005030). Plant Gene Register# PGR97-103. Plant Physiol, 114, 1567-1569.
García-Nebot, M. J., Recio, I., & Hernández-Ledesma, B. (2014). Antioxidant activity and protective effects of peptide lunasin against oxidative stress in intestinal Caco-2 cells. Food and Chemical Toxicology, 65, 155–161.
Gidlöf, O., Sathanoori, R., Magistri, M., Faghihi, M. A., Wahlestedt, C., Olde, B., & Erlinge, D. (2015). Extracellular uridine triphosphate and adenosine triphosphate attenuate endothelial inflammation through miR-22-mediated ICAM-1 inhibition. Journal of vascular research, 52(2), 71-80.
Gonzalez de Mejia, E., Vásconez, M., de Lumen, B. O., & Nelson, R. (2004). Lunasin concentration in different soybean genotypes, commercial soy protein, and isoflavone products. Journal of agricultural and food chemistry, 52(19), 5882-5887.
Grundy, S. M. (2016). Metabolic syndromeupdate. Trends in Cardiovascular Medicine, 26(4), 364-373.
Gu, L., Wang, Y., Xu, Y., Tian, Q., Lei, G., Zhao, C., Gao, Z., Pan, Q., Zhao, W., Nong, L., & Tan, S. (2017). Lunasin functionally enhances LDL uptake via inhibiting PCSK9 and enhancing LDLR expression in vitro and in vivo. Oncotarget, 8(46), 80826-80840.
Guijarro-Díez, M., García, M. C., Crego, A. L., & Marina, M. L. (2014). Off-line two dimensional isoelectrofocusing-liquidchromatography/mass spectrometry (time of flight) for thedetermination of the bioactive peptide lunasin. Journal of Chromatography A, 1371, 117–124.
Guillén, A., Granados, S., Rivas, K. E., Estrada, O., Echeverri, L. F., & Balcázar, N. (2015). Antihyperglycemic activity of Eucalyptus tereticornis in insulin-resistant cells and a nutritional model of diabetic mice. Advances in pharmacological sciences, 2015.
Herna´ndez-Ledesma, B., Hsieh, C.-C., & Lumen, B. O. d. (2009). Lunasin, a novel seed peptide for cancer prevention. Peptides, 30, 426–430.
Hernández-Ledesma, B., Hsieh, C.-C., & Lumen, B. O. d. (2009). Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochemical and Biophysical Research Communications, 390, 803–808.
Hsieh, C.-C., Hern´andez-Ledesma, B., & Lumen, B. O. d. (2010). Soybean Peptide Lunasin Suppresses In Vitro and In Vivo 7,12-Dimethylbenz-[a]anthracene-Induced Tumorigenesis. Journal of Food Science, 75(9), H311-316.
Hsieh, C.-C., Herna´ndez-Ledesma, B., Jeong, H. J., Park, J. H., & Lumen, B. O. d. (2010). Complementary Roles in Cancer Prevention: Protease Inhibitor Makes the Cancer Preventive Peptide Lunasin Bioavailable. PLoS ONE, 5(1).
Hsieh, C.-C., Lin, P.-Y., Kuo, C.-H., Wang, Y.-F. Wang. The effects of lunasin on metabolism in high-fat diet-induced obese C57BL/6J mice. Manuscript.
Hsieh, C.-C., Martínez-Villaluenga, C., Lumenc, B. O. d., & Hernández-Ledesmad, B. (2017). Updating the research on the chemopreventive and therapeutic role of the peptide lunasin. Journal of the science of food and agriculture, 98(6), 2070-2079.
Jeong, H. J., Jeong, J. B., Kim, D. S., Park, J. H., Lee, J. B., Kweon, D. H., Chung, G. Y., Seo, E. W., & Lumen, B. O. d. (2007). The cancer preventive peptide lunasin from wheat inhibits core histone acetylation. Cancer Letters, 255, 42–48.
Jeong, H. J., Lam, Y., & de Lumen, B. O. (2002). Barley lunasin suppresses ras-induced colony formation and inhibits core histone acetylation in mammalian cells. Journal of agricultural and food chemistry, 50(21), 5903-5908.
Kahle, M., Horsch, M., Fridrich, B., Seelig, A., Schultheiß, J., Leonhardt, J., Irmler, M., Beckers, J., Rathkolb, B., Wolf, E., & Franke, N. (2013). Phenotypic comparison of common mouse strains developing high-fat diet-induced hepatosteatosis. Molecular metabolism, 2(4), 435-446.
Kahn, S. E., Hull, R. L., & Utzschneider1, K. M. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 444(14), 840-846.
Kałużna-Czaplińska, J., Gątarek, P., Chirumbolo, S., Chartrand, M. S., & Bjørklund, G. (2019). How important is tryptophan in human health?. Critical reviews in food science and nutrition, 59(1), 72-88.
Kant, A. K. (2006). Secular trends in patterns of self-reported food consumption of adult Americans: NHANES 1971–1975 to NHANES 1999–2002. The American journal of clinical nutrition, 84(5), 1215–1223.
Karacor, K., & Cam, M. (2015). Effects of oleic acid. Medical Science and Discovery, 2, 125-132.
Kim, J., & Samson, S. L. (2014). Cardiovascular effects of incretin therapy in diabetes care. Metabolic syndrome and related disorders, 12(6), 303-310.
Kim, S., Go, G. W., & Imm, J. Y. (2017). Promotion of glucose uptake in C2C12 myotubes by cereal flavone Tricin and its underlying molecular mechanism. Journal of agricultural and food chemistry, 65(19), 3819-3826.
Klein-Wieringa, I. R., Andersen, S. N., Kwekkeboom, J. C., Giera, M., Lange-Brokaar, B. J. E. d., Osch, G. J. V. M. v., Zuurmond, A. N., Stojanovic-Susulic, V., Nelissen, R. G. H. H., Pijl, H., Huizinga, T. W. J., Kloppenburg, M., Toes, R. E. M., & Ioan-Facsinay, A. (2013). Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids. Journal of immunology, 191, 1356-1363.
Koumanov, F., Jin, B., Yang, J., & Holman, G. D. (2005). Insulin signaling meets vesicle traffic of GLUT4 at a plasma-membrane-activated fusion step. Cell metabolism, 2(3), 179-189.
La Frano, M. R., Hernandez-Carretero, A., Weber, N., Borkowski, K., Pedersen, T. L., Osborn, O., & Newman, J. W. (2017). Diet-induced obesity and weight loss alter bile acid concentrations and bile acid–sensitive gene expression in insulin target tissues of C57BL/6J mice. Nutrition research, 46, 11-21.
Lai, Y. S., Chen, W. C., Kuo, T. C., Ho, C. T., Kuo, C. H., Tseng, Y. J., Lu, K. H., Lin, S. H., Panyod, C. H., & Sheen, L. Y. (2015). Mass-spectrometry-based serum metabolomics of a C57BL/6J mouse model of high-fat-diet-induced non-alcoholic fatty liver disease development. Journal of agricultural and food chemistry, 63(35), 7873-7884.
Lee, L. S., Choi, J. H., Sung, M. J., Hur, J. Y., Hur, H. J., Park, J. D., Kim, Y. C., Gu, E. J., Min, B., & Kim, H. J. (2015). Green tea changes serum and liver metabolomic profiles in mice with high‐fat diet‐induced obesity. Molecular nutrition & food research, 59(4), 784-794.
Lee, Y., Kwon, E. Y., & Choi, M. S. (2018). Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice. International journal of molecular sciences, 19(10), 3281.
Lemieux, I., Lamarche, B. t., Couillard, C., Pascot, A. s., Cantin, B., Bergeron, J., Dagenais, G. R., & Despre´s, J. P. (2001). Total Cholesterol/HDL Cholesterol Ratio vs LDL Cholesterol/HDL Cholesterol Ratio as Indices of Ischemic Heart Disease Risk in Men. Archives of internal medicine, 161(22), 2685-2692.
Li, S., Zhou, T., Li, C., Dai, Z., Che, D., Yao, Y., Li, L., Ma, J., Yang, X., & Gao, G. (2014). High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner. PloS one, 9(5), e97330.
Lin, H. V., Efanov, A. M., Fang, X., Beavers, L. S., Wang, X., Wang, J., Valcarcel, I. C. G., & Ma, T. (2016). GPR142 controls tryptophan-induced insulin and incretin hormone secretion to improve glucose metabolism. PloS one, 11(6), e0157298.
Lowell, B. B., & Shulman, G. I. (2005). Mitochondrial dysfunction and type 2 diabetes. Science, 307(5708), 384-387.
Ma, H., & Patti, M. E. (2014). Bile acids, obesity, and the metabolic syndrome. Best practice & research Clinical gastroenterology, 28(4), 573-583.
Mangge, H., Summers, K. L., Meinitzer, A., Zelzer, S., Almer, G., Prassl, R., Schnedl, W. J., Reininghaus, E., Paulmichl, K., Weghuber, D., & Fuchs, D. (2014). Obesity‐related dysregulation of the Tryptophan–Kynurenine metabolism: Role of age and parameters of the metabolic syndrome. Obesity, 22(1), 195-201.
Mohiti-Ardekani, J., Asadi, S., Ardakani, A. M., Rahimifard, M., Baeeri, M., & Momtaz, S. (2019). Curcumin increases insulin sensitivity in C2C12 muscle cells via AKT and AMPK signaling pathways. Cogent Food & Agriculture, 5(1), 1577532.
Nicholson, J. K., & Lindon, J. C. (2008). Systems biology: metabonomics. Nature, 455(7216), 1054.
Nishitani, S., Fukuhara, A., Jinno, Y., Kawano, H., Yano, T., Otsuki, M., & Shimomura, I. (2018). Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid. Experimental and Clinical Endocrinology & Diabetes.
Odani, S., Koide, T., & Ono, T. (1987). Amino Acid Sequence of a Soybean (Glycine max) Seed Polypeptide Having a Poly(L-Aspartic Acid) Structure. The Journal of Biological Chemistry, 262(22), 10502-10505.
Ormazabal, V., Nair, S., Elfeky, O., Aguayo, C., Salomon, C., & Zuñiga, F. A. (2018). Association between insulin resistance and the development of cardiovascular disease. Cardiovascular diabetology, 17(1), 122.
P.Dia, V., & deMejia, E. G. (2010). Lunasin promotes apoptosis in human colon cancer cells by mitochondrial pathway activation and induction of nuclear clusterin expression. Cancer Letters, 295(1), 44-53.
Pabona, J. M. P., Dave, B., Su, Y., Montales, M. T. E., Lumen, B. O. d., Mejia, E. G. d., Rahal, O. M., & Simmen, R. C. M. (2013). The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein. Gene Nutrition, 8, 79–90.
Pan, Z., & Raftery, D. (2007). Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Analytical and bioanalytical chemistry, 387(2), 525-527.
Park, H. S., Hur, H. J., Kim, S. H., Park, S. J., Hong, M. J., Sung, M. J., Kwon, D. Y., & Kim, M. S. (2016). Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet‐induced obese mice. Molecular nutrition & food research, 60(9), 1944-1955.
Park, H., Park, K. T., Park, E., Kim, S., Choi, M., Liu, K. H., & Lee, C. (2017). Mass spectrometry-based metabolomic and lipidomic analyses of the effects of dietary platycodon grandiflorum on liver and serum of obese mice under a high-fat diet. Nutrients, 9(1), 71.
Park, S., Sadanala, K. C., & Kim, E. K. (2015). A metabolomic approach to understanding the metabolic link between obesity and diabetes. Molecules and cells, 38(7), 587.
Petrasek, J., Iracheta‐Vellve, A., Saha, B., Satishchandran, A., Kodys, K., Fitzgerald, K. A., Kurt-Jones, E. A., & Szabo, G. (2015). Metabolic danger signals, uric acid and ATP, mediate inflammatory cross‐talk between hepatocytes and immune cells in alcoholic liver disease. Journal of leukocyte biology, 98(2), 249-256.
Prentice, A. M. (2006). The emerging epidemic of obesity in developing countries. International Journal of Epidemiology, 35, 93–99.
Price, S. J., Pangloli, P., Krishnan, H. B., & Dia, V. P. (2016). Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis. Food Research International, 90, 205–215. Raheja, U. K., Fuchs, D., Giegling, I., Brenner, L. A., Rovner, S. F., Mohyuddin, I., Weghuber, D., Mangge, H., Rujescu, D., & Postolache, T. T. (2015). In psychiatrically healthy individuals, overweight women but not men have lower tryptophan levels. Pteridines, 26(2), 79-84.
Rossmeisl, M., Rim, J. S., Koza, R. A., & Kozak, L. P. (2003). Variation in type 2 diabetes-related traits in mouse strains susceptible to diet-induced obesity. Diabetes, 52(8), 1958-1966.
Satapati, S., Sunny, N. E., Kucejova, B., Fu, X., He, T. T., Méndez-Lucas, A., Shelton, J. M., Perales, J. C., Browning, J. D., & Burgess, S. C. (2012). Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver. Journal of lipid research, 53(6), 1080-1092.
Sezer, H. (2017). Insulin resistance, obesity and lipotoxicity. Obesity and Lipotoxicity, 277-304.
Shen, Y., Honma, N., Kobayashi, K., Jia, L. N., Hosono, T., Shindo, K., Ariga, T., & Seki, T. (2014). Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling. PLoS One, 9(2), e87894.
Shidal, C., Inaba, J.-I., Yaddanapudi, K., & Davis, K. R. (2017). The soy-derived peptide Lunasin inhibits invasive potential of melanoma initiating cells. Oncotarget, 8(15), 25525-25541.
Spiegelman, P. P. (2003). Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine Reviews, 24, 78-90.
Ueda, Y., Iwakura, H., Bando, M., Doi, A., Ariyasu, H., Inaba, H., Morita, S., & Akamizu, T. (2018). Differential role of GPR142 in tryptophan-mediated enhancement of insulin secretion in obese and lean mice. PloS one, 13(6), e0198762.
Uratsuji, H., Tada, Y., Kawashima, T., Kamata, M., Hau, C. S., Asano, Y., Sugaya, M., Kadono, T., Asahina, A., Sato, S., & Tamaki, K. (2012). P2Y6 Receptor Signaling Pathway Mediates Inflammatory Responses Induced by Monosodium Urate Crystals. The Journal of Immunology, 188, 436-444.
Van der Greef, J., & Smilde, A. K. (2005). Symbiosis of chemometrics and metabolomics: past, present, and future. Journal of Chemometrics: A Journal of the Chemometrics Society, 19(5‐7), 376-386.
Vaziri, N. D., & Liang, K. (2004). Effects of HMG-CoA Reductase Inhibition on Hepatic Expression of Key Cholesterol-Regulatory Enzymes and Receptors in Nephrotic Syndrome. American Journal of Nephrology, 24, 606–613.
Walker, A., Pfitzner, B., Neschen, S., Kahle, M., Harir, M., Lucio, M., Moritz, F., Tziotis, D., Witting, M., Rothballer, M., & Engel, M. (2014). Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet. The ISME journal, 8(12), 2380.
Wang, C.-Y., & Liao, J. K. (2012). A Mouse Model of Diet-Induced Obesity and Insulin Resistance. Methods Mol Biol. Author manuscript, 821, 421–433.
Wang, S., Wu, C., Li, X., Zhou, Y., Zhang, Q., Ma, F., Wei, J., Zhang, X., & Guo, P. (2017). Syringaresinol-4-O-β-d-glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes. Acta pharmaceutica sinica B, 7(4), 453-460.
Watson, R. T., & Pessin, J. E. (2001). Intracellular organization of insulin signaling and GLUT4 translocation. Recent progress in hormone research, 56, 175-193.
Wende, A. R., Symons, J. D., & Abel, E. D. (2012). Mechanisms of lipotoxicity in the cardiovascular system. Current hypertension reports, 14(6), 517-531.
Williams, L. M., Campbell, F. M., Drew, J. E., Koch, C., Hoggard, N., Rees, W. D., Kamolrat, T., Ngo, H. T., Steffensen, I. L., Gray, S. R., & Tups, A. (2014). The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases. PloS one, 9(8), e106159.
Wishart, D. S., Tzur, D., Knox, C., Eisner, R., Guo, A. C., Young, N., Cheng, D., Jewell, K., Arndt, D., Sawhney, S., & Fung, C. (2007). HMDB: the human metabolome database. Nucleic acids research, 35(suppl_1), D521-D526.
World Health Organization. 2018 Fact sheets. Detail. Obesity and overweight. Retrieved October 20, 2018, from https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Xia, J., Sinelnikov, I. V., Han, B., & Wishart, D. S. (2015). MetaboAnalyst 3.0—making metabolomics more meaningful. Nucleic acids research, 43(W1), W251-W257.
Yoshitomi, H., Tsuru, R., Li, L., Zhou, J., Kudo, M., Liu, T., & Gao, M. (2017). Cyclocarya paliurus extract activates insulin signaling via Sirtuin1 in C2C12 myotubes and decreases blood glucose level in mice with impaired insulin secretion. PloS one, 12(8), e0183988.
Zheng, X., Zhou, K., Zhang, Y., Han, X., Zhao, A., Liu, J., Qu, L., Ge, K., Huang, F., Hernandez, B., & Yu, H. (2018). Food withdrawal alters the gut microbiota and metabolome in mice. The FASEB Journal, 32(9), 4878-4888.
Zhu, Y., Li, H., & Wang, X. (2017). Lunasin abrogates monocytes to endothelial cells. Molecular Immunology, 92, 146–150.