臺灣博碩士論文加值系統

本實驗著主要探討幾丁寡醣對於正常飲食狀態與高脂飲食狀態的大白鼠，肝臟脂質代謝的作用之機制，並比較高分子量幾丁聚醣與幾丁寡醣對於肝臟脂質過氧化影響之差異。本研究可分為兩個部分，第一部分為幾丁寡醣對正常飲食大鼠脂質過氧化之影響，以 20隻六週齡雄性 Sprague Dawley (SD)大鼠進行實驗，本次實驗分成兩組，分別為 (1) 正常控制組 (Normal control diet, NC)、(2) 幾丁寡醣組 (CC : control diet + 5% Chitosan oligosaccharides)，實驗進行十二週，實驗結果顯示正常飲食中添加5% 幾丁寡醣，對於大鼠脂質代謝與肝臟脂質過氧化程度不會造成影響。第二部分為幾丁寡醣對於高脂飲食大鼠脂質代謝與脂質過氧化之影響，以 32 隻六週齡雄性 SD大鼠進行實驗，本次實驗分成兩組，分為 (1) 正常控制組 (Normal control diet, NC)、(2) 高脂飲食組 (High fat diet, HF)、(3) 幾丁聚醣組 (HC: high fat diet + 5% High molecular weight chitosan)、(4) 幾丁寡醣組 (CO : high fat diet+ 5% Chitosan oligosaccharides)，實驗進行十二週，實驗結果顯示，高脂飲食中添加5%幾丁寡醣肝臟方面可以透過活化AMPK，降低PPARγ蛋白表現量，進而抑制FAS與HMGCR的活性，降低肝臟中總膽固醇與三酸甘油酯的濃度。脂肪組織方面可以透過增加脂解速率、降低LPL 活性，來降低脂肪組織中三酸甘油酯濃度，並透過降低腸道fabp2 與 fatp4 mRNA的表現量減少脂質吸收，對於肝臟抗氧化酵素GPx、SOD與肝臟脂質過氧化物生成沒有影響，但會使血漿中的AST活性上升，目前尚無法推測其機制。綜合上述結果，本研究中幾丁聚醣與幾丁寡醣，在改善脂質代謝機制不盡相同，腸道方面，幾丁聚醣主要利用其物理特性增加脂質排泄，達到抑制脂質吸收作用，幾丁寡醣則是透過降低腸道 fabp2 與 fatp4 mRNA 的表現量減少脂質吸收。肝臟方面，幾丁聚醣與幾丁寡醣皆可以降低肝臟脂質生合成，兩者間以幾丁聚醣改善肝臟脂質堆積的效果較好，此外幾丁聚醣可以促進肝臟抗氧化酵素GPx與SOD，降低肝臟脂質過氧化物產生，而幾丁寡醣則不會影響肝臟脂質過氧化程度。


關鍵詞：幾丁聚醣、幾丁寡醣、脂質代謝、肝臟脂質過氧化

Abstract
This study was designed to investigate the effects of chitosan oligosaccharides on lipid metabolism in high fat diet and normal diet fed rats, and compare effect of chitosan oligosaccharides and chitosan on liver lipid peroxidation in rats. There are two parts of experiments in this study. In the experiment I, rats are divided into two groups: (1) Normal control diet (NC). (2) Normal control diet + 5% chitosan oligosaccharide (CC). The experimental period was 12 weeks. The results showed that chitosan oligosaccharide at 5% didn't have effect on lipid metabolism and liver lipid peroxidation in normal diet fed rat. In the experiment II, rats are divided into four groups: (1) Normal control diet (NC). (2) High fat diet (HF). (3) High fat diet + 5% high molecular weight chitosan (HC). (4) High fat diet + 5% chitosan oligosaccharide (CO). The experimental period was 12 weeks. In present, supplementation of chitosan oligosaccharide promoted liver pAMPKα which could significantly decrease lipogenesis-associated protein (PPARγ) expressions in liver. Chitosan oligosaccharide supplementation significantly decreased TC and TG accumulation in liver by inhibiting the activity of ACC, FAS, HMCGR which were regulated by lipogenesis-associated protein. Chitosan oligosaccharide supplementation significantly decreased the accumulation of TG in perirenal adipose tissue via inhibiting LPL activity and elevating lipolysis rate. In intestinal, chitosan oligosaccharide supplementation significantly inhibited the expressions of fabp2 and fatp4 mRNA to decrease intestinal absorption of lipids. However, chitosan oligosaccharide didn't have effect on the activity of GPx, SOD and the concentration of MDA, 4-HNE in liver. Moreover, supplementation of chitosan oligosaccharide increased the activity of AST, and without understanding its physiological mechanism. The results showed that several aspects of lipid metabolism are different in chitosan oligosaccharides and chitosan. The chitosan oligosaccharides and chitosan inhibited intestinal absorption of lipids with different way. The chitosan inhibited intestinal absorption of lipids by physical properties. The chitosan oligosaccharides inhibited intestinal absorption of lipids by decreasing the expressions of fabp2 and fatp4 mRNA. Both chitosan and chitosan oligosaccharides could reduce lipid synthesis in the liver. The effect of chitosan on improving liver lipid accumulation is better than chitosan oligosaccharides. Chitosan could promote antioxidant enzymes and reduce the concentration of lipid peroxide production in liver, while chitosan oligosaccharides didn't affect liver lipid peroxidation.

Keywords: chitosan, chitosan oligosaccharide, lipid metabolism
and liver lipid peroxidation

目錄
摘要 II
Abstract III
圖目錄 VI
表目錄 VII
詞彙縮寫表 VIII
第一章、 前言 1
第二章、文獻探討 2
第一節、 幾丁聚醣及幾丁寡醣 2
1. 幾丁質及幾丁聚醣 2
2. 幾丁寡醣 6
第二節、 脂質代謝 (Lipid metabolism) 7
1. 高脂飲食 7
2. 脂肪組織 8
3. 脂質代謝相關酵素 9
4. AMP-activated protein kinase (AMPK) 之簡介 10
第三節、 脂質過氧化 13
1. 脂質過氧化物生成過程 13
2. 抗氧化防禦系統 13
3. 粒線體對脂質的調控 14
第三章、實驗動機與目的 16
第四章、幾丁寡醣對正常飲食大鼠脂質過氧化之影響 17
第一節、 材料方法 17
1. 實驗流程 17
2. 實驗材料 18
3. 實驗方法 20
第二節、 實驗結果 27
1. 實驗期間大白鼠體重、攝食量和食物利用率 27
2. 實驗結束犧牲時大白鼠組織臟器重量 27
3. 犧牲後大白鼠血漿中葡萄糖、脂質含量與肝臟脂質含量 27
4. 犧牲後大白鼠血漿中AST、ALT活性及TNF-Α含量 27
5. 犧牲後大白鼠肝臟中 TBARS 濃度與抗氧化酵素活性 27
6. 犧牲後大白鼠脂肪組織脂質含量 27
7. 大白鼠糞便重量與脂質濃度測定結果 28
第五章、比較幾丁聚醣及幾丁寡醣對於高脂飲食大鼠脂質代謝之影響 29
第一節、 材料方法 29
1. 實驗流程 29
2. 實驗材料 31
3. 實驗方法 33
第二節、 實驗結果 50
1. 實驗期間大白鼠體重、攝食量和食物利用率 50
2. 實驗結束犧牲時大白鼠組織臟器重量 50
3. 犧牲後大白鼠血漿生化指標測定 50
4. 犧牲後大白鼠肝臟生化指標測定 51
5. 大白鼠腎周脂肪組織脂質含量、LPL活性與脂解速率 52
6. 大白鼠小腸黏膜 mRNA 表現量 52
7. 大白鼠糞便重量及脂質濃度測定 53
第六章、討論 54
第一節、 幾丁聚醣及幾丁寡醣對於體重及組織臟器之影響 54
第二節、 幾丁聚醣及幾丁寡醣對大鼠脂質代謝之影響 54
1. 血漿脂質代謝之影響 54
2. 肝臟脂質代謝之影響 55
3. 脂肪組織代謝之影響 56
4. 腸道脂質吸收之影響 56
5. 糞便脂質濃度之影響 57
第三節、 幾丁聚醣及幾丁寡醣對肝臟脂質過氧化之影響 57
第七章、結論 58
第八章、參考文獻 60

第八章、參考文獻
行政院衛生福利部，2017，民國106年健康促進統計年報。
姚賢宗，2003。幾丁聚醣對大白鼠脂質代謝及腸道生理的影響。國立台灣海洋大學食品科學系博士論文。
馮仕安，2016。幾丁聚醣及其衍生物對大白鼠血糖及血脂之研究。國立臺灣海洋大學食品科學系碩士論文，基隆。
施景銘，2017。比較高、低分子量幾丁聚醣對於大白鼠脂質代謝與脂肪肝之研究。國立臺灣海洋大學食品科學系碩士論文，基隆。
張恬嘉，2014。幾丁聚醣與魚油改善高脂飲食引起的大白鼠肥胖及脂肪肝之研究。國立臺灣海洋大學食品科學系碩士論文，基隆。
陳艷琳，2013。幾丁聚醣改善高脂飲食誘發大白鼠肥胖及脂肪肝之機制探討。國立臺灣海洋大學食品科學系碩士論文，基隆。
顏采恩，2018。比較幾丁聚醣及其衍生物對大白鼠脂質代謝之研究。國立臺灣海洋大學食品科學系碩士論文，基隆。
Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A., Wakil, S. J. (2001). Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science, 291(5513), 2613-2616.
Baier, L. J., Bogardus, C., Sacchettini, J. C. (1996). A polymorphism in the human intestinal fatty acid binding protein alters fatty acid transport across Caco-2 cells. Journal of Biological Chemistry, 217, 10892-10896.
Bergamini, C. M., Gambetti, S., Dondi, A., Cervellati, C. (2004). Oxygen, reactive oxygen species and tissue damage. Current pharmaceutical design, 10(14), 1611-1626.
Berger, J. J., and Barnard, R. J. (1999). Effect of diet on fat cell size and hormone-sensitive lipase activity. Journal of Applied Physiology, 87(1), 227-232.
Carlson, S. E. and Goldfarb, S. (1977). A sensitive enzymatic method for the determination of free and esterified tissue cholesterol. Clinica Chimica Acta, 79, 575-582.
Carmen, G. Y., and Víctor, S. M. (2006). Signalling mechanisms regulating lipolysis. Cellular Signalling, 18(4), 401-408.
Cho, E. J., Rahman, A., Kim, S. W., Baek, Y. M., Hwang, H. J., Oh, J. Y., Hwang, H. S., Lee, S. H., Yun, J. W. (2008). Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes. Journal of Microbiology and Biotechnology, 18(1), 80-87.
Chae, S. Y., Son, S., Lee, M., Jang, M. K., Nah, J. W. (2005). Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier. Journal of Controlled Release, 109(1-3), 330-344.
Chae, S. Y., Jang, M. K., and Nah, J. W. (2005). Influence of molecular weight on oral absorption of water soluble chitosans. Journal of Controlled Release, 102(2), 383-394.
Chancharme, L., Thérond, P., Nigon, F., Zarev, S., Mallet, A., Bruckert, E., Chapman, M. J. (2002). LDL particle subclasses in hypercholesterolemia: molecular determinants of reduced lipid hydroperoxide stability. Journal of Lipid Research, 43(3), 453-462.
Chiang, M. T., Yao, H. T., Chen, H. C. (2000). Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol. Biosci Biotechnol Biochem, 64, 965-971.
Chen, Y. D. I., Risser, T. R., Cully, M., & Reaven, G. M. (1979). Is the hypertriglyceridemia associated with insulin deficiency caused by decreased lipoprotein lipase activity?. Diabetes, 28(10), 893-898.
Cockcroft, J. R., Chowienczyk, P. J., Ritter, J. M., Lehmann, E. D., Hopkins, K. D., Parker, J. R. Gosling, R. G. (1995). Hyperlipidaemia, hypertension, and coronary heart disease. Lancet, 345, 862-863.
Cruz, W. S., Kwon, G., Marshall, C. A., McDaniel, M. L., Semenkovich, C. F. (2001). Glucose and insulin stimulate heparin-releasable lipoprotein lipase activity in mouse islets and INS-1 cells: a potential link between insulin resistance and β-cell dysfunction. Journal of Biological Chemistry, 276, 12162-12168.
Davies, D. H. and Hayes, E. R. (1988). Determination of the degree of acetylation of chitin and chitosan. Methods in Enzymology, 161, 442-446.
Darlington, G. J., Ross, S. E., MacDougald, O. A. (1998). The role of C/EBP genes in adipocyte differentiation. Journal of Biological Chemistry, 273(46), 30057-30060.
Deuchi, K., Kanauchi, O., Imasato, Y., Kobayashi, E. (1994). Decreasing effect of chitosan on the apparent fat digestibility by rats fed on a high-fat diet. Bioscience, Biotechnology, and Biochemistry, 58(9), 1613-1616.
Department of Health and Humam Services and Department of Agriculture. (2015). 2015-2020 Dietary guidelines for Americans 8th edition. http://health.gov/dietaryguidelines/2015/guidelines/ download on 2017/07/30.
Ebihara, K., and Nakamoto, Y. (2001). Effect of the particle size of corn bran on the plasma cholesterol concentration, fecal output and cecal fermentation in rats. Nutrition Research, 21(12), 1509-1518.
Esterbauer, H., Schaur, R. J., Zollner, H. (1991). Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology and Medicine, 11(1), 81-128.
Esterbauer, H., Eckl, P., Ortner, A. (1990). Possible mutagens derived from lipids and lipid precursors. Mutation Research/Reviews in Genetic Toxicology, 238(3), 223-233.
Fabbrini, E., Mohammed, B. S., Magkos, F., Korenblat, K. M., Patterson, B. W. & Klein, S. (2008). Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology, 134, 424-431.
Fernández-Hernando, C., Suárez, Y., Rayner, K. J., and Moore, K. J. (2011). MicroRNAs in lipid metabolism. Current Opinion in Lipidology, 22(2), 86.
Fernandes, J. C., Spindola, H., De Sousa, V., Santos-Silva, A., Pintado, M. E., Malcata, F. X., and Carvalho, J. E. (2010). Anti-inflammatory activity of chitooligosaccharides in vivo. Marine Drugs, 8(6), 1763-1768.
Fisher, R. M., Coppack, S. W., Humphreys, S. M., Gibbons, G. F., Frayn, K. N. (1995). Human triacylglycerol-rich lipoprotein subfractions as substrates for lipoprotein lipase. Clinica Chimica Acta, 236(1), 7-17.
Fonseca-Alaniz, M. H., Takada, J., Alonso-Vale, M. I. C., Lima, F. B. (2007). Adipose tissue as an endocrine organ: from theory to practice. Jornal de Pediatria, 83(5), 192-203.
Folch, J., Lees, M., and Sloane Stanley, G. H. (1957). A simple method for the isolation and purification of total lipids from animal tissues. The Journal of Biological Chemistry, 226, 497-509.
Fungwe, T. V., Cagen, L., Wilcox, H. G., Heimberg, M. (1992). Regulation of hepatic secretion of very low density lipoprotein by dietary cholesterol. Journal of Lipid Research, 33(2), 179-191.
Fukada, Y., Kimura, K., Ayaki, Y. (1991). Effect of chitosan feeding on intestinal bile acid metabolism in rats. Lipids, 26(5), 395-399.
Gao, S., He, L., Ding, Y., Liu, G. (2010). Mechanisms underlying different responses of plasma triglyceride to high-fat diets in hamsters and mice: roles of hepatic MTP and triglyceride secretion. Biochemical and Biophysical Research Communications, 398(4), 619-626.
Gallaher, D. D., Gallaher, C. M., Mahrt, G. J., Carr, T. P., Hollingsaesd, C. H., Hesslink, R., Wise, J. (2002). A glucomannan and chitosan fiber supplementdecreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans. Journal of the American College of Nutrition, 21, 428-433.
Hardie, D. G. (2014). AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels. Annual Review of Nutrition, 34, 31-55.
Hardie, D. G. (2004). The AMP-activated protein kinase pathway–new players upstream and downstream. Journal of Cell Science, 117(23), 5479-5487.
Hatefi, Y. (1985). The mitochondrial electron transport and oxidative phosphorylation system. Annual Review of Biochemistry, 54(1),1015-1069.
Holm, C. (2003). Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochemical Society Transactions, 31, 1120-1124.
Horton, J. D., Goldstein, J. L., Brown, M. S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. The Journal of Clinical Investigation, 109(9), 1125-1131.
Huang, L., Chen, J., Cao, P., Pan, H., Ding, C., Xiao, T., Zhang, P., Guo, J., Su, Z. (2015). Anti-obese effect of glucosamine and chitosan oligosaccharide in high-fat diet-induced obese rats. Marine Drugs, 13(5), 2732-2756.
Huang, R., Mendis, E., Rajapakse, N., and Kim, S. K. (2006). Strong electronic charge as an important factor for anticancer activity of chitooligosaccharides (COS). Life Sciences, 78(20), 2399-2408.
Islam, S., Rahman Bhuiyan, M. A., Islam, M. N. (2016). Chitin and chitosan: structure, properties and applications in biomedical engineering. Journal of Polymers and the Environment, 25, 1-13.
Jennings, C. D., Boleyn, K., Bridges, S. R., Wood, P. J., Anderson, J. W. (1988). A comparison of the lipid-lowering and intestinal morphological effects of cholestyramine, chitosan, and oat gum in rats. Proceedings of the Society for Experimental Biology and Medicine, 189, 13-20.
Jeon, Y. J., and Kim, S. K. (2000). Production of chitooligosaccharides using an ultrafiltration membrane reactor and their antibacterial activity. Carbohydrate Polymers, 41(2), 133-141.
Johnson, F., and Giulivi, C. (2005). Superoxide dismutases and their impact upon human health. Molecular Aspects of Medicine, 26(4-5), 340-352.
Ju, C., Yue, W., Yang, Z., Zhang, Q., Yang, X., Liu, Z., Zhang, F. (2010). Antidiabetic effect and mechanism of chitooligosaccharides. Biological and Pharmaceutical Bulletin, 33(9), 1511-1516.
Jung, E. J., Youn, D. K., Lee, S. H., No, H. K., Ha, J. G., Prinyawiwatkul, W. (2010). Antibacterial activity of chitosans with different degrees of deacetylation and viscosities. International Journal of Food Science and Technology, 45(4), 676-682.
Kanauchi, O., Deuchi, K., Imasato, Y., Shizukuishi, M., Kobayashi, E. (1995). Mechanism for the inhibition of fat digestion by chitosan and for the synergistic effect of ascorbate. Bioscience, Biotechnology, and Biochemistry, 59(5), 786-790.
Kerner, J., and Hoppel, C. (2000). Fatty acid import into mitochondria. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1486(1), 1-17.
Kim, J., Yang, G., Kim, Y., Kim, J., Ha, J. (2016). AMPK activators: mechanisms of action and physiological activities. Experimental and Molecular Medicine, 48(4), 1-12.
Knorr, D. (1984). Use of chitinous polymers in food: a challenge for food research and development. Food Technology (USA).
Krüner, G. and Westernhagen, H. V. (1999). Sources of measurement error in assays of EROD activity of fish for biological effects monitoring. Helgoland Marine Research, 53(3), 250.
Kurita, K. (2006). Chitin and chitosan: functional biopolymers from marine crustaceans. Marine Biotechnology, 8, 203-226.
Kushnareva, Y., Murphy, A. N., Andreyev, A. (2002). Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD (P)+ oxidation–reduction state. Biochemical Journal, 368(2), 545-553.
Kumar, M. N. R. (2000). A review of chitin and chitosan applications. Reactive and Functional Polymers, 46(1), 1-27.
Kusunoki, M., Hara, T., Tsutsumi, K., Nakamura, T., Miyata, T., Sakakibara, F., Sakamoto, S., Ogawa, H., Nakaya, Y., Storlien, L. H. (2000). The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet. Diabetologia, 43(7), 875-880.
Lehoux, J. G. and Grondin, F. (1993). Some effect of chitosan on live function in the rat. Endocrinogy, 132, 1078-1084.
Liu, J., Zhang, J., Xia, W. (2008). Hypocholesterolaemic effects of different chitosan samples in vitro and in vivo. Food Chemistry, 107, 419-425.
Lim, B. O., Yamada, K., Nonaka, M., Kuramoto, Y., Hung, P., Sugano, M. (1997). Dietary fibers modulate indices of intestinal immune function in rats. The Journal of Nutrition, 127, 663-667.
Lin, E. C., Fernandez, M. L., McNamara, D. J. (1992). Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs. The Journal of Nutrition, 122(10), 2019-2029.
Lodhi, G., Kim, Y. S., Hwang, J. W., Kim, S. K., Jeon, Y. J., Je, J. Y., Ahn, C. B., Moon, S. H., Jeon, B. T., Park, P. J. (2014). Chitooligosaccharide and its derivatives: preparation and biological applications. Biomed Research International, 2014.
Mashige, F., Tanaka, N., Maki, A., Kamei, S., Yamanaka, M. (1981). Direct spectrophotometry of total bile acids in serum. Clinical Chemistry, 27(8), 1352-1356.
Maezaki, Y., Tsuji, K., Nakagawa, Y., Kawai, Y., Akimoto, M., Tsugita, T., Takekawa, W., Terada, A., Hara, H., Mitsuoka, T. (1993). Hypocholesterolemic effect of chitosan in adult males. Bioscience, Biotechnology, and Biochemistry, 57(9), 1439-1444.
McBride, H. M., Neuspiel, M., Wasiak, S.（2006）. Mitochondria: more than just a powerhouse. Current Biology, 16(14), R551-R560.
Milger, K., Herrmann, T., Becker, C., Gotthardt, D., Zickwolf, J., Ehehalt, R., Watkins, P. A., Stremmel, W., Füllekrug, J. (2006). Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4. Journal of Cell Science, 119, 4678-4688.
Mourya, V. K., Inamdar, N. N., Choudhari, Y. M. (2011). Chitooligosaccharides: Synthesis, characterization and applications. Polymer Science Series A, 53(7), 583-612.
Mosca, C. L., Marshall, J. A., Grunwald, G. K., Cornier, M. A., Baxter, J. (2004). Insulin resistance as a modifier of the relationship between dietary fat intake and weight gain. International Journal of Obesity, 28, 803-812.
Mokdad, A. H., Ford, E. S., Bowman, B. A., Dietz, W. H., Vinicor, F., Bales, V. S., Marks, J. S. (2003). Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. Journal of the American Medical Association, 289(1), 76-79.
Musso G, Gambino R, Cassader M. (2009). Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD). Progress in Lipid Research, 48(1), 1-26.
Nawar, W. W. Lipid in “Food Chemistry”. Fennema, O. R. Ed., Marcel Dekker, INC., New York. 1985, 139-244.
Nepokroeff, C. M., Lakshmanan, M. R., and Porter, J. W. (1975). Fatty acid synthase from rat liver. Methods in Enzymology, 35, 37-44.
Ngo, D. N., Lee, S. H., Kim, M. M., and Kim, S. K. (2009). Production of chitin oligosaccharides with different molecular weights and their antioxidant effect in RAW 264.7 cells. Journal of Functional Foods, 1(2), 188-198.
Noeman, S. A., Hamooda, H. E., Baalash, A. A. (2011). Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetology & Metabolic Syndrome, 3(1), 17.
Ouchi, N., Parker, J. L., Lugus, J. J., Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nature Reviews Immunology, 11(2), 85.
Pan, H., Yang, Q., Huang, G., Ding, C., Cao, P., Huang, L., Xiao, T., Xiao, T., Guo, J., Su, Z. (2016). Hypolipidemic effects of chitosan and its derivatives in hyperlipidemic rats induced by a high-fat diet. Food & Nutrition Research, 60(1), 31137.
Panith, N., Wichaphon, J., Lertsiri, S., Niamsiri, N. (2016). Effect of physical and physicochemical characteristics of chitosan on fat-binding capacities under in vitro gastrointestinal conditions. LWT-Food Science and Technology, 71, 25-32.
Pagano, C., Soardo, G., Esposito, W., Fallo, F., Basan, L., Vettor, R. (2005). Plasma adiponectin is decreased in nonalcoholic fatty liver disease. European Journal of Endocrinology, 152(1), 113-118.
Pastore, A., Federici, G., Bertini, E., Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clinica Chimica Acta, 333(1), 19-39.
Ramsay, T. G. (1996). Fat cells. Endocrinology and Metabolism Clinics of North America, 25(4), 847-870.
Rinaudo, M. (2006). Chitin and chitosan: Properties and applications. Progress in Polymer Science, 31, 603-632.
Rocha, A., Bolin, A. P., Cardoso, C. A. L., Otton, R. (2016). Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity. European Journal of Nutrition, 55(7), 2231-2244.
Rolo, A. P., Teodoro, J. S., Palmeira, C. M. (2012). Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radical Biology and Medicine, 52(1), 59-69.
Robertson, G., Leclercq, I., Farrell, G. C. (2001). II. Cytochrome P-450 enzymes and oxidative stress. American Journal of Physiology-Gastrointestinal and Liver Physiology, 281(5), G1135-G1139.
Rutter, G. A., Xavier, G., D. S., Leclerc, I. (2003). Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochemical Journal, 375(1), 1-16.
Scheffler, I. E.（2001）. Mitochondria make a come back. Advanced Drug Delivery Reviews, 49(1）, 3-26.
Senevirathne, M., Ahn, C. B., Je, J. Y. (2011). Hepatoprotective effect of chitooligosaccharides against tert-butylhydroperoxide-induced damage in Chang liver cells. Carbohydrate Polymers, 83(2), 995-1000.
Sell, H., Berger, J. P., Samson, P., Castriota, G., Lalonde, J., Deshaies, Y., Richard, D. (2004). Peroxisome proliferator-activated receptor γ agonism increases the capacity for sympathetically mediated thermogenesis in lean and ob/ob mice. Endocrinology, 145(8), 3925-3934.
Sessions, V. A., and Salter, A. M. (1994). The effects of different dietary fats and cholesterol on serum lipoprotein concentrations in hamsters. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 1211(2), 207-214.
Steinberg, G. R., and Kemp, B. E. (2009). AMPK in health and disease. Physiological Reviews, 89(3), 1025-1078.
Stryer L. (1998) Biochemistry, 3rd edn. Academic press, U S A.
Su, C. L., Sztalryd, C., Contreras, J. A., Holm, C., Kimmel, A. R., Londos, C. (2003). Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes. Journal of Biological Chemistry, 278(44), 43615-43619.
Sugano, M., Fujikawa, T., Hiratsuji, Y., Nakashima, K., Fukuda, N., Hasegawa, Y. (1980). A novel use of chitosan as a hypocholesterolemic agent in rats. The American Journal of Clinical Nutrition, 33, 787-793.
Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A. (2006). A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-α and n-3 polyunsaturated fatty acid treatment on liver injury. The American Journal of Pathology, 169(3), 846-860.
Takehisa, F., and Suzuki, Y. (1990). Effect of guar gum and cholestyramine on plasma lipoprotein cholesterol in rats. Journal of Japanese Society of Nutrition and Food Science, 43, 269-274.
Tomas, E., Tsao, T. S., Saha, A. K., Murrey, H. E., Zhang, C. C., Itani, S. I., Lodish, H. F., Ruderman, N. B. (2002). Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation. Proceedings of the National Academy of Sciences, 99(25), 16309-16313.
Trayhurn, P., and Beattie, J. H. (2001). Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society, 60(3), 329-339.
Van de Velde, K., and Kiekens, P. (2004). Structure analysis and degree of substitution of chitin, chitosan and dibutyrylchitin by FT-IR spectroscopy and solid state 13C NMR. Carbohydrate Polymers, 58(4), 409-416.
Wang, B., Zhang, S., Wang, X., Yang, S., Jiang, Q., Xu, Y., Xia, W. (2017). Transcriptome analysis of the effects of chitosan on the hyperlipidemia and oxidative stress in high-fat diet fed mice. International Journal of Biological Macromolecules, 102, 104-110.
Westerterp-Plantenga, M. S. (2001). Analysis of energy density of food in relation to energy intake regulation in human subjects. British Journal of Nutrition, 85, 351-361.
Wu, Q., Lin, D., Yao, S. (2014). Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes. Marine Drugs, 12, 6236-6253.
Xu, G., Huang, X., Qiu, L., Wu, J. Hu, Y. (2007). Mechanism study of chitosan on lipid metabolism in hyperlipidemic rats. Asia Pacific Journal of Clinical Nutrition, 16, 313-317.
Zeng L, Qin C, Wang W, Chi W, Li W (2008) Absorption and distribution of chitosan in mice after oral administration. Carbohydrate Polymers 71. 435–440.
Zhang, Y., Ahmad, K. A., Khan, F. U., Yan, S., Ihsan, A. U., Ding, Q. (2019). Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway. Chemico-Biological Interactions, 350(25), 54-64.
Zong, C., Yu, Y., Song, G., Luo, T., Li, L., Wang, X., Qin, S. (2012). Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice. Experimental Biology and Medicine, 237, 194-200.