Antidiabetic and Antihyperlipidemic Effects of Clitocybe nuda on Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice
The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract of Clitocybe nuda (CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0?g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin ( , , , resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation. 1. Introduction The prevalence of diabetes mellitus (DM) represents a significant and growing global health problem. Type 2 diabetes mellitus (T2D) accounts for 90% to 95% of all patients [1]. Diabetes mellitus is characterized by hyperglycemia that involves abnormalities in either insulin secretion or action at peripheral tissues, resulting in reducing insulin sensitivity at skeletal muscle and adipose and liver tissues, which represents insulin resistance. Both genetic (heredity) and environmental factors (obesity and leisure life style) play an important role in T2D. Clitocybe nuda (Fr.) Bigelow and Smith (Lepista nuda, commonly known as wood blewit or blue stalk mushroom) is an
References
[1]
S. O'Rahilly, R. C. Turner, and D. R. Matthews, “Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes,” The New England Journal of Medicine, vol. 318, no. 19, pp. 1225–1230, 1988.
[2]
L. Barros, B. A. Venturini, P. Baptista, L. M. Estevinho, and I. C. F. R. Ferreira, “Chemical composition and biological properties of Portuguese wild mushrooms: a comprehensive study,” Journal of Agricultural and Food Chemistry, vol. 56, no. 10, pp. 3856–3862, 2008.
[3]
B. Dulger, C. C. Ergul, and F. Gucin, “Antimicrobial activity of the macrofungus Lepista nuda,” Fitoterapia, vol. 73, no. 7-8, pp. 695–697, 2002.
[4]
M. A. Murcia, M. Martínez-Tomé, A. M. Jiménez, A. M. Vera, M. Honrubia, and P. Parras, “Antioxidant activity of edible fungi (truffles and mushrooms): losses during industrial processing,” Journal of Food Protection, vol. 65, no. 10, pp. 1614–1622, 2002.
[5]
N. Mercan, M. E. Duru, A. Turkoglu, K. Gezer, I. Kivrak, and H. Turkoglu, “Antioxidant and antimicrobial properties of ethanolic extract from Lepista nuda (Bull.) Cooke,” Annals of Microbiology, vol. 56, no. 4, pp. 339–344, 2006.
[6]
J. T. Chen, H. J. Su, and J. W. Huang, “Isolation and identification of secondary metabolites of Clitocybe nuda inhibition of zoospore germination of Phytophthora capsici,” Journal of Agricultural and Food Chemistry, vol. 60, no. 30, pp. 7341–7344, 2012.
[7]
C. Kandaswami and E. Middleton, “Flavonoids as antioxidants,” in Natural Antioxidants: Chemistry, Health Effects and Practical Applications, F. Shahidi, Ed., pp. 174–194, The American Oil Chemists Society, Champaign, lll, USA, 1997.
[8]
Y. S. Velioglu, G. Mazza, L. Gao, and B. D. Oomah, “Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products,” Journal of Agricultural and Food Chemistry, vol. 46, no. 10, pp. 4113–4117, 1998.
[9]
D. Xu, Y. Sheng, Z.-Y. Zhou, R. Liu, Y. Leng, and J.-K. Liu, “Sesquiterpenes from cultures of the basidiomycete Clitocybe conglobata and their 11β-hydroxysteroid dehydrogenase inhibitory activity,” Chemical and Pharmaceutical Bulletin, vol. 57, no. 4, pp. 433–435, 2009.
[10]
D. J. St. Jean Jr., M. Wang, and C. Fotsch, “Inhibitors of 11β-HSD1: a potential treatment for the metabolic syndrome,” Current Topics in Medicinal Chemistry, vol. 8, no. 17, pp. 1508–1523, 2008.
[11]
J. Berger, C. Biswas, P. P. Vicario, H. V. Strout, R. Saperstein, and P. F. Pilch, “Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting,” Nature, vol. 340, no. 6228, pp. 70–72, 1989.
[12]
B. B. Kahn, S. W. Cushman, and J. S. Flier, “Regulation of glucose transporter-specific mRNA levels in rat adipose cells with fasting and refeeding. Implications for in vivo control of glucose transporter number,” The Journal of Clinical Investigation, vol. 83, no. 1, pp. 199–204, 1989.
[13]
R. T. Watson and J. E. Pessin, “Intracellular organization of insulin signaling and GLUT4 translocation,” Recent Progress in Hormone Research, vol. 56, pp. 175–194, 2001.
[14]
S. Sujatha, S. Anand, K. N. Sangeetha et al., “Biological evaluation of (3β)-STIGMAST-5-EN-3-OL as potent anti-diabetic agent in regulating glucose transport using in vitro model,” International Journal of Diabetes Mellitus, vol. 2, no. 2, pp. 101–109, 2010.
[15]
M. Foretz, N. Toleux, B. Guigas et al., “Regulation of energy metabolism by AMPK: a novel therapeutic approach for the treatment of metabolic and cardiovascular diseases,” Médecine/Sciences, vol. 22, no. 4, pp. 381–388, 2006.
[16]
B. Viollet, L. Lantier, J. Devin-Leclerc et al., “Targeting the AMPK pathway for the treatment of type 2 diabetes,” Frontiers in Bioscience, vol. 14, no. 9, pp. 3380–3400, 2009.
[17]
T. Tsuda, Y. Ueno, H. Aoki et al., “Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes,” Biochemical and Biophysical Research Communications, vol. 316, no. 1, pp. 149–157, 2004.
[18]
A. E. Petro, J. Cotter, D. A. Cooper, J. C. Peters, S. J. Surwit, and R. S. Surwit, “Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6J mouse,” Metabolism, vol. 53, no. 4, pp. 454–457, 2004.
[19]
G. Zhou, R. Myers, Y. Li et al., “Role of AMP-activated protein kinase in mechanism of metformin action,” The Journal of Clinical Investigation, vol. 108, no. 8, pp. 1167–1174, 2001.
[20]
S. C. Stein, A. Woods, N. A. Jones, M. D. Davison, and D. Cabling, “The regulation of AMP-activated protein kinase by phosphorylation,” Biochemical Journal, vol. 345, no. 3, pp. 437–443, 2000.
[21]
T. Swain and W. E. Hills, “The phenolic constituents of Punnus domestica. I.—the quantitative analysis of phenolic constituents,” Journal of the Science of Food and Agriculture, vol. 10, no. 1, pp. 63–68, 1959.
[22]
M. Dubois, K. A. Gilles, J. K. Hamilton, P. A. Rebers, and F. Smith, “Colorimetric method for determination of sugars and related substances,” Analytical Chemistry, vol. 28, no. 3, pp. 350–356, 1956.
[23]
C.-C. Shih, C.-H. Lin, and W.-L. Lin, “Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet,” Diabetes Research and Clinical Practice, vol. 81, no. 2, pp. 134–143, 2008.
[24]
C.-C. Shih, C.-H. Lin, and J.-B. Wu, “Eriobotrya japonica improves hyperlipidemia and reverses insulin resistance in high-fat-fed mice,” Phytotherapy Research, vol. 24, no. 12, pp. 1769–1780, 2010.
[25]
Q. W. Shen, C. S. Jones, N. Kalchayanand, M. J. Zhu, and M. Du, “Effect of dietary α-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice,” Journal of Animal Science, vol. 83, no. 11, pp. 2611–2617, 2005.
[26]
M. A. Iglesias, J.-M. Ye, G. Frangioudakis et al., “AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats,” Diabetes, vol. 51, no. 10, pp. 2886–2894, 2002.
[27]
J.-M. Ye, N. B. Ruderman, and E. W. Kraegen, “AMP-activated protein kinase and malonyl-CoA: targets for treating insulin resistance?” Drug Discovery Today, vol. 2, no. 2, pp. 157–163, 2005.
[28]
H.-G. Joost, G. I. Bell, J. D. Best et al., “Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators,” American Journal of Physiology: Endocrinology and Metabolism, vol. 282, no. 4, pp. E974–E976, 2002.
[29]
P. Daisy, K. Balasubramanian, M. Rajalakshmi, J. Eliza, and J. Selvaraj, “Insulin mimetic impact of Catechin isolated from Cassia fistula on the glucose oxidation and molecular mechanisms of glucose uptake on Streptozotocin-induced diabetic Wistar rats,” Phytomedicine, vol. 17, no. 1, pp. 28–36, 2010.
[30]
A. Barthel and D. Schmoll, “Novel concepts in insulin regulation of hepatic gluconeogenesis,” American Journal of Physiology: Endocrinology and Metabolism, vol. 285, no. 4, pp. E685–E692, 2003.
[31]
Y. Pan, J.-M. Zheng, H.-Y. Zhao, Y.-J. Li, H. Xu, and G. Wei, “Relationship between drug effects and particle size of insulin-loaded bioadhesive microspheres,” Acta Pharmacologica Sinica, vol. 23, no. 11, pp. 1051–1056, 2002.
[32]
T. Hayashi, M. F. Hirshman, E. J. Kurth, W. W. Winder, and L. J. Goodyear, “Evidence for 5′AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport,” Diabetes, vol. 47, no. 8, pp. 1369–1373, 1998.
[33]
E. J. Kurth-Kraczek, M. F. Hirshman, L. J. Goodyear, and W. W. Winder, “5′AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle,” Diabetes, vol. 48, no. 8, pp. 1667–1671, 1999.
[34]
P. A. Lochhead, I. P. Salt, K. S. Walker, D. G. Hardie, and C. Sutherland, “5-Aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase,” Diabetes, vol. 49, no. 6, pp. 896–903, 2000.
[35]
W. W. Winder, “AMP-activated protein kinase: possible target for treatment of type 2 diabetes,” Diabetes Technology & Therapeutics, vol. 2, no. 3, pp. 441–448, 2000.
[36]
Y. D. Kim, K.-G. Park, Y.-S. Lee et al., “Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP,” Diabetes, vol. 57, no. 2, pp. 306–314, 2008.
[37]
S. Huang and M. P. Czech, “The GLUT4 glucose transporter,” Cell Metabolism, vol. 5, no. 4, pp. 237–252, 2007.
[38]
Y. Li, S. Xu, M. M. Mihaylova et al., “AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice,” Cell Metabolism, vol. 13, no. 4, pp. 376–388, 2011.
[39]
N. Henin, M.-F. Vincent, H. E. Gruber, and G. Van den Berghe, “Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP- activated protein kinase,” The FASEB Journal, vol. 9, no. 7, pp. 541–546, 1995.
[40]
D. M. Muoio, K. Seefeld, L. A. Witters, and R. A. Coleman, “AMP-activated kinase reciprocally regulates triacylglycerol synthesis and fatty acid oxidation in liver and muscle: evidence that sn-glycerol-3-phosphate acyltransferase is a novel target,” Biochemical Journal, vol. 338, no. 3, pp. 783–791, 1999.
[41]
G. F. Merrill, E. J. Kurth, D. G. Hardie, and W. W. Winder, “AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle,” American Journal of Physiology: Endocrinology and Metabolism, vol. 273, no. 6, pp. E1107–E1112, 1997.
[42]
N. Musi, “AMP-activated protein kinase and type 2 diabetes,” Current Medicinal Chemistry, vol. 13, no. 5, pp. 583–589, 2006.
[43]
R. Zimmermann, J. G. Strauss, G. Haemmerle et al., “Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase,” Science, vol. 306, no. 5700, pp. 1383–1386, 2004.
[44]
M. P. Gaidhu, S. Fediuc, N. M. Anthony et al., “Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL,” The Journal of Lipid Research, vol. 50, no. 4, pp. 704–715, 2009.
[45]
M. Kato, N. Higuchi, and M. Enjoji, “Reduced hepatic expression of adipose tissue triglyceride lipase and CGI-58 may contribute to the development of non-alcoholic fatty liver disease in patients with insulin resistance,” Scandinavian Journal of Gastroenterology, vol. 43, no. 8, pp. 1018–1019, 2008.
[46]
H. Shimano, N. Yahagi, M. Amemiya-Kudo et al., “Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes,” The Journal of Biological Chemistry, vol. 274, no. 50, pp. 35832–35839, 1999.
[47]
D. D. Patel, B. L. Knight, D. Wiggins, S. M. Humphreys, and G. F. Gibbons, “Disturbances in the normal regulation of SREBP-sensitive genes in PPARa-deficient mice,” Journal of Lipid Research, vol. 42, no. 3, pp. 328–337, 2001.
[48]
A. Suzuki, S. Okamoto, S. Lee, K. Saito, T. Shiuchi, and Y. Minokoshi, “Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor α gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the α2 form of AMP-activated protein kinase,” Molecular and Cellular Biology, vol. 27, no. 12, pp. 4317–4327, 2007.
[49]
T. Tsuda, F. Horio, K. Uchida, H. Aoki, and T. Osawa, “Dietary cyanidin 3-O-β-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice,” The Journal of Nutrition, vol. 133, no. 7, pp. 2125–2130, 2003.
[50]
I. D. Postescu, C. Tatomir, G. Chereches et al., “Spectroscopic characterization of some grape extracts with potential role in tumor growth inhibition,” Journal of Optoelectronics and Advanced Materials, vol. 9, no. 3, pp. 564–567, 2007.
[51]
H.-C. Su, L.-M. Hung, and J.-K. Chen, “Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats,” American Journal of Physiology: Endocrinology and Metabolism, vol. 290, no. 6, pp. E1339–E1346, 2006.
[52]
V. R. Drel and N. Sybirna, “Protective effects of polyphenolics in red wine on diabetes associated oxidative/nitrative stress in streptozotocin-diabetic rats,” Cell Biology International, vol. 34, no. 12, pp. 1147–1153, 2010.
[53]
R. T. R. Tan, S. Mohamed, G. F. Samaneh, M. M. Noordin, Y. M. Goh, and M. Y. A. Manap, “Polyphenol rich oil palm leaves extract reduce hyperglycaemia and lipid oxidation in STZ-rats,” International Food Research Journal, vol. 18, no. 1, pp. 179–188, 2011.