Abstract
In this study, we investigated the effects of silymarin (SM) on gluconeogenesis during exercise in rats. After 4 weeks of exercise, blood samples, liver, and skeletal muscle tissues were collected, and the levels of triglycerides (TG), lactate, peroxisome proliferator activated receptor gamma (PPARγ), phosphoenol pyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase 4 (PDK4), and phosphorylated 5-AMP activated protein kinase (AMPK) were measured. The TG and lactate level of the serum were reduced. In addition, the expression of Akt, PEPCK, and PPARγ in liver was decreased as well as the expression of AMPK in muscle. On the contrary, the level of PDK4 in muscle was increased. These results showed that that administration of SM ameliorated exerciseinduced gluconeogenesis and β-oxidation through the regulation of PPARγ, PEPCK, and PDK4. Thus, intake of SM during exercise may improve endurance by modulating of the metabolism of glucose, lipids, and lactate.
This is a preview of subscription content, access via your institution.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
References
Fritsche L, Weigert C, Haring HU, Lehmann R. How insulin receptor substrate proteins regulate the metabolic capacity of the liver-implications for health and disease. Curr. Med. Chem. 15: 1316–1329 (2008)
Blair JB, Cimbala MA, James ME. Hepatic pyruvate kinase. Quantitative measurements of phosphorylation in vitro and in the isolated rat hepatocyte. J. Biol. Chem. 257: 7595–7602 (1982)
Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, Spiegelman B, Montminy M. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413: 179–183 (2001)
Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch: Possible roles in type 2 diabetes. Am. J. Physiol. 277: 1–10 (1999)
Ceddia RB, Sweeney G. Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells. J. Physiol. 555: 409–421 (2004)
Huang B, Wu P, Bowker-Kinley MM, Harris RA. Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 51: 276–283 (2002)
Huang YJ, Walker D, Chen W, Klingbeil M, Komuniecki R. Expression of pyruvate dehydrogenase isoforms during the aerobic/anaerobic transition in the development of the parasitic nematode Ascaris suum: Atered stoichiometry of phosphorylation/inactivation. Arch. Biochem. Biophys. 352: 263–270 (1998)
Wu P, Inskeep K, Bowker-Kinley MM, Popov KM, Harris RA. Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes. Diabetes 48: 1593–1599 (1999)
Wu P, Sato J, Zhao Y, Jaskiewicz J, Popov KM, Harris RA. Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart. Biochem. J. 329: 197–201 (1998)
Harris RA, Huang B, Wu P. Control of pyruvate dehydrogenase kinase gene expression. Adv. Enzyme Regul. 41: 269–288 (2001)
Gray SR, Baker G, Wright A, Fitzsimons CF, Mutrie N, Nimmo MA, The effect of a 12 week walking intervention on markers of insulin resistance and systemic inflammation. Prev. Med. 48: 39–44 (2009)
Murase T, Haramizu S, Shimotoyodome A, Nagasawa A, Tokimitsu I. Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288: 708–715 (2005)
Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 61: 2035–2063 (2001)
Szewieczek J, Dulawa J, Strzalkowska D, Batko-Szwaczka A, Hornik B. Normal insulin response to short-term intense exercise is abolished in Type 2 diabetic patients treated with gliclazide. J. Diabetes Complicat. 23: 380–386 (2009)
Kim SH, Lee S, Suk K, Bark H, Jun CD, Kim DK, Choi CH, Yoshimura T. Discoidin domain receptor 1 mediates collagen-induced nitric oxide production in J774A.1 murine macrophages. Free Radic. Biol. Med. 42: 343–352 (2007)
Kim SH, Jun CD, Suk K, Choi BJ, Lim H, Park S, Lee SH, Shin HY, Kim DK, Shin TY. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol. Sci. 91: 123–131 (2006)
LeBlanc PJ, Peters SJ, Tunstall RJ, Cameron-Smith D, Heigenhauser GJ. Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle. J. Physiol. 557: 559–570 (2004)
Pilegaard H, Neufer PD. Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise. Proc. Nutr. Soc. 63: 221–226 (2004)
Wu LY, Juan CC, Hwang LS, Hsu YP, Ho PH, Ho LT. Green tea supplementation ameliorates insulin resistance and increases glucose transporter IV content in a fructose-fed rat model. Eur. J. Nutr. 43: 116–124 (2004)
Wolfram S, Raederstorff D, Preller M, Wang Y, Teixeira SR, Riegger C, Weber P. Epigallocatechin gallate supplementation alleviates diabetes in rodents. J. Nutr. 136: 2512–2518 (2006)
Vengerovskii AI, Khazanov VA, Eskina KA, Vasilyev KY. Effects of silymarin (hepatoprotector) and succinic acid (bioenergy regulator) on metabolic disorders in experimental diabetes mellitus. Bull. Exp. Biol. Med. 144: 53–56 (2007)
Holloszy JO, Oscai LB, Don IJ, Mole PA. Mitochondrial citric acid cycle and related enzymes: Adaptive response to exercise. Biochem. Biophys. Res. Commun. 40: 1368–1373 (1970)
Murase T, Haramizu S, Shimotoyodome A, Tokimitsu I, Hase T. Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290: 1550–1556 (2006)
Wahren J, Ekberg K. Splanchnic regulation of glucose production. Annu. Rev. Nutr. 27: 329–345 (2007)
De Feo P, Di Loreto C, Lucidi P, Murdolo G, Parlanti N, De Cicco A, Piccioni F, Santeusanio F. Metabolic response to exercise. J. Endocrinol. Invest. 26: 851–854 (2003)
Stephens FB, Norton L, Jewell K, Chokkalingam K, Parr T, Tsintzas K. Basal and insulin-stimulated pyruvate dehydrogenase complex activation, glycogen synthesis and metabolic gene expression in human skeletal muscle the day after a single bout of exercise. Exp. Physiol. 95: 808–818 (2010)
Jeoung NH, Wu P, Joshi MA, Jaskiewicz J, Bock CB, Depaoli-Roach AA, Harris RA. Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation. Biochem. J. 397: 417–425 (2006)
Hwang B, Jeoung NH, Harris RA. Pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency attenuates the long-term negative effects of a highsaturated fat diet. Biochem. J. 423: 243–252 (2009)
Jeoung NH, Harris RA. Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice. Am. J. Physiol. Endocrinol. Metab. 295: 46–54 (2008)
Chen N, Bezzina R, Hinch E, Lewandowski PA, Cameron-Smith D, Mathai ML, Jois M, Sinclair AJ, Begg DP, Wark JD, Weisinger HS, Weisinger RS. Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a highfat diet. Nutr. Res. 29: 784–793 (2009)
Danesi F, Di Nunzio M, Boschetti E, Bordoni A. Green tea extract selectively activates peroxisome proliferator-activated receptor beta/delta in cultured cardiomyocytes. Br. J. Nutr. 101: 1736–1739 (2009)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Choi, EJ., Kim, EK., Jeoung, N.H. et al. Effect of silymarin on gluconeogenesis and lactate production in exercising rats. Food Sci Biotechnol 25 (Suppl 1), 119–124 (2016). https://doi.org/10.1007/s10068-016-0108-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10068-016-0108-5
Keywords
- silymarin
- exercise
- gluconeogenesis
- β-oxidation