リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice

Igarashi, Yuichi Iida, Shiho Dai, Jian Huo, Jia Cui, Xiaoran Sawashita, Jinko Mori, Masayuki Miyahara, Hiroki Higuchi, Keiichi 信州大学 DOI:34022607

2023.01.26

概要

Aims: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism.

Main methods: Female obese, type 2 diabetic KK-Ay mice were fed diets supplemented with 0.3% or 0.8% GRO (w/w) for 4–12 weeks. Mice were euthanized and autopsied at 20 weeks old. The effects of GRO on lipid and glucose metabolism were evaluated by measuring physiological and biochemical markers using mRNA sequencing, quantitative reverse-transcription PCR, and western blot analyses.

Key findings: Compared to mice fed the control diet, GRO-supplemented mice had reduced body and white ad- ipose tissue weights, serum levels of triglycerides and cholesterol, and improved glucose tolerance, while food intake was not affected. We found remarkable reductions in the gene expression levels of stearoyl-coenzyme A desaturase 1 (Scd1) and pyruvate dehydrogenase kinase isoenzyme 4 (Pdk4) in the liver, in addition to decreased expression of fatty acid synthase (Fasn) in inguinal white adipose tissue (iWAT). These results suggest that GRO supplementation improves lipid profiles via reduced de novo lipogenesis in the liver and white adipose tissue. Glucose metabolism may also be improved by increased glycolysis in the liver.

Significance: Our analysis of long-term supplementation of GRO in obese and diabetic mice should provide novel insight into preventing insulin resistance and metabolic syndromes.

参考文献

[1] P.G. Kopelman, Obesity as a medical problem, Nature 404 (2000) 635–643.

[2] P. Zimmet, Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted? J. Intern. Med. 247 (2000) 301–310.

[3] P. Zimmet, K.G. Alberti, J. Shaw, Global and societal implications of the diabetes epidemic, Nature 414 (2001) 782–787.

[4] B.B. Lowell, G.I. Shulman, Mitochondrial dysfunction and type 2 diabetes, Science 307 (2005) 384–387.

[5] P. Dandona, A. Aljada, A. Bandyopadhyay, Inflammation: the link between insulin resistance, obesity and diabetes, Trends Immunol. 25 (2004) 4–7.

[6] Y. Yagishita, A. Uruno, T. Fukutomi, R. Saito, D. Saigusa, J. Pi, A. Fukamizu, F. Sugiyama, S. Takahashi, M. Yamamoto, Nrf2 improves leptin and insulin resistance provoked by hypothalamic oxidative stress, Cell Rep. 18 (2017) 2030–2044.

[7] J. Ye, Mechanisms of insulin resistance in obesity, Front. Med. 7 (2013) 14–24.

[8] A.J. Cruz-Jentoft, A.A. Sayer, Sarcopenia, Lancet 393 (2019) 2636–2646.

[9] S. Shibata, A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice, Yakugaku Zasshi 120 (2000) 849–862.

[10] M. Kuroda, Y. Mimaki, Y. Sashida, T. Mae, H. Kishida, T. Nishiyama, M. Tsukagawa, E. Konishi, K. Takahashi, T. Kawada, K. Nakagawa, M. Kitahara, Phenolics with PPAR-gamma ligand-binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice, Bioorg. Med. Chem. Lett. 13 (2003) 4267–4272.

[11] T.Y. Wu, T.O. Khor, C.L. Saw, S.C. Loh, A.I. Chen, S.S. Lim, J.H. Park, L. Cai, A. regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis, AAPS J. 13 (2011) 1–13.

[12] H. Haraguchi, N. Yoshida, H. Ishikawa, Y. Tamura, K. Mizutani, T. Kinoshita, Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra, J. Pharm. Pharmacol. 52 (2000) 219–223.

[13] T. Fukai, A. Marumo, K. Kaitou, T. Kanda, S. Terada, T. Nomura, Anti-Helicobacter pylori flavonoids from licorice extract, Life Sci. 71 (2002) 1449–1463.

[14] C.K. Lee, K.K. Park, S.S. Lim, J.H. Park, W.Y. Chung, Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer, Biol. Pharm. Bull. 30 (2007) 2191–2195.

[15] K. Nakagawa, M. Kitano, H. Kishida, T. Hidaka, K. Nabae, M. Kawabe, K. Hosoe, 90-Day repeated-dose toxicity study of licorice flavonoid oil (LFO) in rats, Food Chem. Toxicol. 46 (2008) 2349–2357.

[16] K. Nakagawa, H. Kishida, N. Arai, T. Nishiyama, T. Mae, Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y) mice, Biol. Pharm. Bull. 27 (2004) 1775–1778.

[17] F. Aoki, S. Honda, H. Kishida, M. Kitano, N. Arai, H. Tanaka, S. Yokota, K. Nakagawa, T. Asakura, Y. Nakai, T. Mae, Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice, Biosci. Biotechnol. Biochem. 71 (2007) 206–214.

[18] Y. Tominaga, K. Nakagawa, T. Mae, M. Kitano, S. Yokota, T. Arai, H. Ikematsu, S. Inoue, Licorice flavonoid oil reduces total body fat and visceral fat in overweight subjects: a randomized, double-blind, placebo-controlled study, Obes. Res. Clin. Pract. 3 (2009) I–IV.

[19] M. Kuroda, Y. Mimaki, S. Honda, H. Tanaka, S. Yokota, T. Mae, Phenolics from Glycyrrhiza glabra roots and their PPAR-gamma ligand-binding activity, Bioorg. Med. Chem. 18 (2010) 962–970.

[20] Y. Yoshioka, Y. Yamashita, H. Kishida, K. Nakagawa, H. Ashida, Licorice flavonoid oil enhances muscle mass in KK-A(y) mice, Life Sci. 205 (2018) 91–96.

[21] K. Sawada, Y. Yamashita, T. Zhang, K. Nakagawa, H. Ashida, Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cells, Mol. Cell. Endocrinol. 393 (2014) 99–108.

[22] M. Nishimura, Breeding of mice strains for diabetes mellitus, Exp. Anim. 18 (1969) 147–157.

[23] A.J. King, The use of animal models in diabetes research, Br. J. Pharmacol. 166 (2012) 877–894.

[24] Z. Xu, J. Huo, X. Ding, M. Yang, L. Li, J. Dai, K. Hosoe, H. Kubo, M. Mori, K. Higuchi, J. Sawashita, Coenzyme Q10 improves lipid metabolism and ameliorates obesity by regulating CaMKII-mediated PDE4 inhibition, Sci. Rep. 7 (2017) 8253.

[25] M. Kitada, Y. Ogura, D. Koya, Rodent models of diabetic nephropathy: their utility and limitations, Int. J. Nephrol. Renov. Dis. 9 (2016) 279–290.

[26] S.A. Bustin, V. Benes, J. Garson, J. Hellemans, J. Huggett, M. Kubista, R. Mueller, T. Nolan, M.W. Pfaffl, G. Shipley, C.T. Wittwer, P. Schjerling, P.J. Day, M. Abreu, B. Aguado, J.F. Beaulieu, A. Beckers, S. Bogaert, J.A. Browne, F. Carrasco-Ramiro, L. Ceelen, K. Ciborowski, P. Cornillie, S. Coulon, A. Cuypers, S. De Brouwer, L. De Ceuninck, J. De Craene, H. De Naeyer, W. De Spiegelaere, K. Deckers, A. Dheedene, K. Durinck, M. Ferreira-Teixeira, A. Fieuw, J.M. Gallup, S. Gonzalo-Flores, K. Goossens, F. Heindryckx, E. Herring, H. Hoenicka, L. Icardi, R. Jaggi, F. Javad, M. Karampelias, F. Kibenge, M. Kibenge, C. Kumps, I. Lambertz, T. Lammens, A. Markey, P. Messiaen, E. Mets, S. Morais, A. Mudarra-Rubio, J. Nakiwala, H. Nelis, P.A. Olsvik, C. P´erez-Novo, M. Plusquin, T. Remans, A. Rihani, P. Rodrigues-Santos, P. Rondou, R. Sanders, K. Schmidt-Bleek, K. Skovgaard, K. Smeets, L. Tabera, S. Toegel, T. Van Acker, W. Van den Broeck, J. Van der Meulen, M. Van Gele, G. Van Peer, M. Van Poucke, N. Van Roy, S. Vergult, J. Wauman, M. Tshuikina-Wiklander, E. Willems, S. Zaccara, F. Zeka, J. Vandesompele, The need for transparency and good practices in the qPCR literature, Nat. Methods 10 (2013) 1063–1067.

[27] M. Miyazaki, H. Sampath, X. Liu, M.T. Flowers, K. Chu, A. Dobrzyn, J.M. Ntambi, Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice, Biochem. Biophys. Res. Commun. 380 (2009) 818–822.

[28] J.M. Ntambi, M. Miyazaki, J.P. Stoehr, H. Lan, C.M. Kendziorski, B.S. Yandell, Y. Song, P. Cohen, J.M. Friedman, A.D. Attie, Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity, Proc. Natl. Acad. Sci. USA 99 (2002) 11482–11486.

[29] J.M. Ntambi, M. Miyazaki, Regulation of stearoyl-CoA desaturases and role in metabolism, Prog. Lipid Res. 43 (2004) 91–104.

[30] G. Jiang, Z. Li, F. Liu, K. Ellsworth, Q. Dallas-Yang, M. Wu, J. Ronan, C. Esau, C. Murphy, D. Szalkowski, R. Bergeron, T. Doebber, B.B. Zhang, Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase- 1, J. Clin. Investig. 115 (2005) 1030–1038.

[31] R. Guti´errez-Ju´arez, A. Pocai, C. Mulas, H. Ono, S. Bhanot, B.P. Monia, L. Rossetti, Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance, J. Clin. Investig. 116 (2006) 1686–1695.

[32] M. Miyazaki, M.T. Flowers, H. Sampath, K. Chu, C. Otzelberger, X. Liu, J. M. Ntambi, Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis, Cell Metab. 6 (2007) 484–496.

[33] S.H. Lee, A. Dobrzyn, P. Dobrzyn, S.M. Rahman, M. Miyazaki, J.M. Ntambi, Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment, J. Lipid Res. 45 (2004) 1674–1682.

[34] M.T. Flowers, J.M. Ntambi, Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism, Curr. Opin. Lipidol. 19 (2014) 248–256.

[35] P. Dobrzyn, A. Dobrzyn, M. Miyazaki, P. Cohen, E. Asilmaz, D.G. Hardie, J. M. Friedman, J.M. Ntambi, Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver, Proc. Natl. Acad. Sci. USA 101 (2004) 6409–6414.

[36] A.L. AM, D.N. Syed, J.M. Ntambi, Insights into stearoyl-CoA desaturase-1 regulation of systemic metabolism, Trends Endocrinol. Metab. 28 (2017) 831–842.

[37] A.M. Hebbachi, B.L. Knight, D. Wiggins, D.D. Patel, G.F. Gibbons, Peroxisome proliferator-activated receptor α deficiency abolishes the response of lipogenic gene expression to re-feeding, Biol. Chem. 283 (2008) 4866–4876.

[38] S. Zhang, M.W. Hulver, R.P. McMillan, M.A. Cline, E.R. Gilbert, The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility, Nutr. Metab. 11 (2014) 10 (Lond.).

[39] J.E. Foley, Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus, Diabetes Care 15 (1992) 773–784.

[40] L. Hue, H. Taegtmeyer, The Randle cycle revisited: a new head for an old hat, Am. J. Physiol. Endocrinol. Metab. 297 (2009) E578–E591.

[41] B. Hwang, N.H. Jeoung, R.A. Harris, Pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency attenuates the long-term negative effects of a high-saturated fat diet, Biochem. J. 423 (2009) 243–252.

[42] R. Tao, X. Xiong, R.A. Harris, M.F. White, X.C. Dong, Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes, PLoS One 8 (2013) 71997.

[43] S. Nishimura, I. Manabe, M. Nagasaki, K. Eto, H. Yamashita, M. Ohsugi, M. Otsu, K. Hara, K. Ueki, S. Sugiura, K. Yoshimura, T. Kadowaki, R. Nagai, CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity, Nat. Med. 15 (2009) 914–920.

[44] H. Kwon, J.E. Pessin, Adipokines mediate inflammation and insulin resistance, Front. Endocrinol. 4 (2013) 71 (Lausanne).

[45] J.W. Lee, S.S. Choe, H. Jang, J. Kim, H.W. Jeong, H. Jo, K.H. Jeong, S. Tadi, M. G. Park, T.H. Kwak, J. Man Kim, D.H. Hyun, J.B. Kim, AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity, J. Lipid Res. 53 (2012) 1277–1286.

[46] Y. Yamashita, H. Kishida, K. Nakagawa, Y. Yoshioka, H. Ashida, Liquorice flavonoid oil suppresses hyperglycaemia accompanied by skeletal muscle myocellular GLUT4 recruitment to the plasma membrane in KK-A(y) mice, Int. J. Food Sci. Nutr. 70 (2019) 294–302.

[47] A. Hattori, M. Takemoto, T. Ishikawa, Y. Maezawa, M. Koshizaka, H. Tokuyama, P. He, H. Kawamura, K. Kobayashi, K. Yokote, Metabolic effects of glabridin in healthy volunteers and patients with type 2 diabetes: a pilot study, Cogent Food Agric. 5 (2019), 1665943.

[48] S.J. Wakil, L.A. Abu-Elheiga, Fatty acid metabolism: target for metabolic syndrome, J. Lipid Res. Suppl. 50 (2009) S138–S143.

[49] M. Roden, G.I. Shulman, The integrative biology of type 2 diabetes, Nature 576 (2019) 51–60.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る