Conjugated linoleic acid supplementation enhances insulin sensitivity and peroxisome proliferator-activated receptor gamma and glucose transporter type 4 protein expression in the skeletal muscles of rats during endurance exercise

Document Type: Original Article

Authors

Institute of Sports Health Science, Sunmoon University, Asan city, Chung Nam, 380-701, S. Korea

Abstract

Objective(s):This study examined whether conjugated linoleic acid (CLA) supplementation affects insulin sensitivity and peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter type 4 (GLUT-4) protein expressions in the skeletal muscles of rats during endurance exercise.
Materials and Methods:Sprague-Dawley male rats were randomly divided into HS (high-fat diet (HFD) sedentary group, n = 8), CS (1.0% CLA supplemented HFD sedentary group, n = 8), and CE (1.0% CLA supplemented HFD exercise group, n = 8). The rats in the CE swam for 60 min a day, 5 days a week for 8 weeks.
Results:The serum glucose and insulin contents and homeostasis model assessment of insulin resistance (HOMA-IR) value of the CS and CE were significantly decreased compared to those of the HS. The PPAR-γ protein expressions in the soleus muscle (SOM) and extensor digitorum longus muscle (EDL) were significantly higher in the CE than in the HS. In addition, the PPAR-γ protein expression in the SOM of the CS was significantly higher than that in the HS. On the other hand, the GLUT-4 protein expression of the SOM in the CE was significantly higher compared to that in the HS. However, there was no significant difference in GLUT-4 protein expression in the EDL among the groups.
Conclusion:CLA supplementation with/without endurance exercise has role in improvement of insulin sensitivity. Moreover, when CLA supplementation was accompanied by endurance exercise, the PPAR-γ protein expression in SOM and EDL and the GLUT-4 protein expression in SOM were enhanced compared with the control group.

Keywords


1.Charlotte AM. Muscle development and obesity. Organosenesis 2008; 4:158-169.

2.David S. Exercise, appetite and appetite-regulation hormones: implications for food intake and weight control. Nutri Metab 2010; 57:36-42.

3.Feinle-Bisset C. Modulation of hunger and satiety: hormones and diet. Curr Opin Clin Nutr Metab Care 2014; 17:458-64.

4.Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet induced obese rats. Lipids Health Dis 2010; 9:81-89.

5.Patric S, Klaas RW. The role of high-fat diet and physical activity in the regulation of body weight. Br J Nutr 2000; 84:417-427.

6.Pescatello LS, VanHeest JL. Physical activity mediates a healthier body weight in the presence of obesity. Br J Sports Med 2000; 34:86-93.

7.Goh VH, Hart WG. Associations of physical exercise as a lifestyle habit with lean and fat body mass and handgrip strength and age in Asian men. Ageing Male 2014; 17:131-135.

8.Calegari VC, Zoppi CC, Rezende LF, Siverira LR, Cameiro EM, Boschero AC. Endurance training activates AMP-activated protein kinase, increases expression of uncoupling protein 2 and reduces insulin secretion form rat pancreatic islets. J Endocrinol 2011; 208:257-264.

9.Hung YH, Linden MA, Gordon A, Rector RS, Buhman KK. Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes. Physiol Rep  2015; 3:e12232.

10.Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med 1998; 49:235-261.

11.Bente K. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 2006; 86:205-243.

12.Gonçalves DC, Lira FS, Carnevali LC Jr, Rosa JC, Pimentel GD, Seelaender M. Conjugated linoleic acid: good or bad nutrient. Diabetol Metab Syndr 2010; 2:62-73.

13.Moon HS, Lee HG, Seo JH, Chung CS, Kim TG, Choi YJ, et al. Antiobesity effect of PEGylated conjugated linoleic acid on high-fat diet induced obese C57BL/6J (ob/ob) mice; attenuation of insulin resistance and enhancement of antioxidant defenses. J Nutr Biochem 2009; 20:187-194.

14.Azain MJ, Hausman DB, Sisk MB, Flatt WP, Jewell DE. Dietary conjugated linoleic acid reduces fat adipose tissue cell size rather than cell number. J Nutr 2000; 130:1548-1554.

15.Angela AW, Aparna P, Li-Fen L, Marths AB. Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice. J Lipid Res 2008; 49:98-106.

16.Jhao J, Tian Y, Xu J, Liu D, Wang X, Zhao B. Endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats. Lipid Health Dis 2011; 10:225-231.

17.Brozinick JT, Etgen GJ, Yaspelkis BB, Kang HY, Ivy JL. Effects of exercise training on muscle GLUT-4 protein content and translocation on obese Zucker rats. Am J Physiol Endocrinol Metab 1993; 265:E419-E427.

18.Dohm GL. Exercise effects on muscle insulin signaling and action invited review; Regulation of skeletal muscle GLUT-4 expression by exercise. J Appl Physiol 2002; 93: 782-787.

19.Hammarstedt A, Anderson CX, Rotter SV, Smith U. The effects of PPAR gamma ligand on the adipose tissue in insulin resistance. Prostaglandins Leukot Essent Fatty Acids 2005; 73:65-75.

20.Kang J, Lee J, Kwon D, Song Y. Effect of Opuntia humifusa supplementation and acute exercise on insulin sensitivity and associations with PPAR-r and PGC-1a protein expression in skeletal muscle of rats. Int J Mol Sci 2013; 4:7140-7154.

21.Rusell AP, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, et al. Endurance training in humans leads to fiber type specific increases in levels of peroxisome proliferator activated receptor gamma coactivator 1 and peroxisome proliferator activated receptor alpha in skeletal muscle. Diabetes 2003; 52: 2874-2881.

22.Hariri N, Thibault L. High-fat diet induced obesity in animal models. Nutr Res Rev 2010; 23:270-299.

23.Kwon DK, Hwang KH, Kim YK, Lee KH, Song YJ. Effects of swimming exercise and soybean supplementation on the immune functions of rats fed a high fat diet. Clin Exp Pharmacol Physiol 2008; 35:638-642.

24.Armstrong RB, Phelps RO. Muscle fiber type composition of the rat hind limb. Am J Anat 1984; 171:259-272.

25.DeLany JP, Blohm F, Truett AA, Scimeca J, West DB. Conjugated linoleic acid reduces body fat content in mice without affecting energy intake. Am J Physiol 1999; 276:R1172-R1177.

26.Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997; 32:853-858.

27.Koba K, Akahoshi A, Yamasaki M, Tanaka K, Yanada K, Iwata T, et al. Dietary conjugated linoleic acid in relation to CLA differently modifies body fat mass and serum and liver lipid levels in rats. Lipids 2002; 37:343-350.

28.Poulos SO, Sisk M, Hausman DB, Azain MJ, Hausman GJ. Pre- and postnatal dietary conjugated linoleic acid alters adipose development, body weight gain and body composition in Sprague-Dawley rats. J Nutr 2001; 131:2722-2731.

29.Kim CH, Youn JH, Park JY, Hong SK, Park KS, Park SW, et al. Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats. Am J Physiol Endocrinol Metab 2000; 278:977-984.

30.Costa-Júnior JM, Ferreira SM, Protzek AO, Santos GJ, Cappelli AP, Silveira LR, et al. Endurance training inhibits insulin clearance and IDE expression in Swiss mice. PLoS One 2015; 10:e0118809.

31.Yamasaki B, Ikeda A, Oji M, Tanaka Y, Hirao A, Kasai M, et al. Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague Dawley rats fad various fat-level diets. Nutrition 2003; 19:30-35.

32.Hariri N, Thibault L. High-fat diet induced obesity in animal models. Nutr Res Rev 2010; 23:270-299.

33.Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet induced obese rats. Lipids Health Dis 2010; 9:81-89.

34.Straczkowski M, Kowaiska I, Dzienis-Straczkowska S, Kinalski M, Górski J, Kinalska L. The effect of exercise training on glucose tolerance and skeletal muscle triacylglycerol content in rats fed with a high-fat diet. Diabetes Metab 2001; 27:19-23.

35.Haghshenas R, Jafari M, Ravasi A, Kordi M, Gilani N, Shariatzadeh M, et al. The effect pf eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma. Iran J Basic Med Sci 2014; 17:237-243.

36.Tarnopolosky M, Zimmer A, Paikin J, Safdar A, Aboud A, Pearce E, et al. Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS One 2007; 2:e99120.

37.Patureau Mirand P, Mosoni L, Arnal-Bagnard MA, Faulconnier Y, Chardigny JM, Chilliard Y. Dietary conjugated linoleic acid has limited effects on tissue protein anabolism in sedentary and exercising adult rats. Reprod Nutr Dev 2006; 46:621-632.

38.Livisay SA, Zhou S, Ip C, Decker EA. Impact of dietary conjugated linoleic acid on the oxidative stability of rat liver microsomes and skeletal muscle homogenates. J Agric Food Chem 2000; 48:4162-4167.

39.Park Y, Albright KJ, Storkson JM, Liu W, Cook ME, Pariza MW. Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids 1999; 34:243-248.

40.Röckl KS, Witczak CA, Goodyear LJ. Signaling mechanisms in skeletal muscle; acute responses and chronic adaptations to exercise. IUBMB Life 2008; 60:145-153.

41.Yoshika Y, Masuda T, Nakano H, Miura H, Nakaya S, Itazawa S, et al. In vitro IH-NMR spectroscopic analysis of metabolites in fast- and slow-twitch muscles of young rats. Magn Reson Med Sci 2002; 1:7-13.

42.Vyas D, Kadegowda AKG, Erdman RA. Dietary conjugated linoleic acid hepatic steatosis: Species-specific effects on liver and adipose lipid metabolism and gene expression. J Nutr Metab 2012; 2012:932928-932940.

43.Kern M, Wells JA, Stephens JM, Elton CW, Friedman JE, Tapscott EB, et al. Insulin responsiveness in skeletal muscle is determined by glucose transporter protein level. Biochem J 1990; 270:397-400.

44.Friedman JE, Sherman WM, Reed MJ, Elton CW, Dohm GL. Exercise training increases glucose transporter protein GLUT-4 in skeletal muscle of obese Zucker rats. FEBS Lett 1990; 268:13-16.

45.Kumar PM, Venkataranganna MV, Manjunath K, Viswanatha GL, Ashok G. Methanolic extract of Momordica cymbalaria enhances glucose uptake in L6 myotubes in vitro by up-regulating PPAR-γ and GLUT-4. Chin J Nat Med 2014; 12:895-900.

46.Li M, Bai Y, Chen C, Cui J, Xu X, Dai Y. Effects of exercise and conjugated linoleic acid on PPARγ in adolescent obese rats. Wei Sheng Yan Jiu 2015; 44:179-184.

47.Li M, Bai Y, Jianfei C, Xiaodong X, Yuanyuan D, Jing Z. Effects of different exercise intensity on PPARγ and relative index in adolescent obesity rats. Wei Sheng Yan Jiu 2014; 43:732-737.

48.Phillippe PM, Laurent M, Marie-Agnes AB, Yannick F, Jean-Michel C, Yves C. Dietary conjugated linoleic acid has limited effects on tissue protein anabolism in sedentary and exercising adult rats. Reprod Nutr Dev 2006; 46:621-632.

49.Lira FS, Yamahita AS, Uchida MC, Zanchi NE, Guaiano B, Martins JE, et al. Low and moderate rather than high intensity strength exercise induces benefit regarding plasma lipid profile. Diabetol Metab Syndr 2010; 2:31-36.

 50.Lillioja S, Young AA. Culter CL. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest 1987; 80:415-424.

51.Henriksson J. Effect of training and nutrition on the development of skeletal muscle. J Sports Sci 1995; 13:S25-30.

52.Kolka CM, Richey JM, Castro AV, Broussard JL, Ionut V, Bergman RN. Lipid-induced insulin resistance does not impair insulin access to skeletal muscle. Am J Physiol Endocrinol Metab 2015; [Epub ahead of print].