Exercise Improved Rat Metabolism by Raising PPAR-α

Abstract

Based on the importance of exercise and crucial role of liver in metabolism, the aim of this study was to determine whether the expression of peroxisome proliferator-activated receptor (PPAR)-α, γ and adiponectin receptor 2 in OLETF rat liver were altered in conjunction with improved metabolism with exercise training. OLETF rats were randomly assigned to 2 groups: sedentary control group (n=26), and long-term exercise-trained group (n=26). Full data were available on 32 OLETF rats (16 for each group). Adiponectin, glucose, insulin, triglyceride and cholesterol were assessed. Livers were taken to determine the expression of PPAR-α, γ and adiponectin receptor 2. Compared with sedentary control group, fasting glucose (9.38±2.99 mmol/L vs. 7.32±1.76 mmol/L, P<0.05), triglyceride (1.73±0.34 mmol/L vs. 0.89±0.12 mmol/L, P<0.05) and cholesterol (4.41±0.75 mmol/L vs. 2.13±0.32 mmol/L, P<0.05) were substantially reduced after exercise, which significantly correlated with increased PPAR-α (P<0.05) in liver. The expression of PPAR-α upstream and target genes, including hepatocyte nuclear factor-4 (HNF4), carnitine palmitoyl transferase 1 (CPT-1), catalase (CAT) and ATPbinding cassette transporter A1 (ABCA1) also increased significantly. Therefore, our findings suggest that increased PPAR-α expression in OLETF rats liver is a contributory factor to the exercise-related improvements in whole-body metabolism.

Key words

PPAR-gamma - adiponectin receptor 2 - OLETF - liver - PPAR-alpha - metabolism

References

• 1 Ferré P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.  Diabetes. 2004;  53 S43-S50
• 2 Gurnell M. Peroxisome proliferator-activated receptor γ and the regulation of adipocyte function: lessons from human genetic studies.  Best Pract Res Clin Endocrinol Metab. 2005;  19 501-523
• 3 Harriss DJ, Atkinson G. International Journal of Sports Medicine-Ethical Standards in Sport and Exercise Science Research.  Int J Sports Med. 2009;  30 701-702
• 4 Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis.  Mol Cell Biol. 2001;  21 1393-1403
• 5 Horowitz JF, Leone TC, Feng W, Kelly DP, Klein S. Effect of endurance training on lipid metabolism in women: a potential role for PPARα in the metabolic response to training.  Am J Physiol. 2000;  279 E348-E355
• 6 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.  Arterioscler Thromb Vasc Biol. 2000;  20 1595-1599
• 7 Iemitsu M, Miyauchi T, Maeda S, Tanabe T, Takanashi M, Irukayama-Tomobe Y, Sakai S, Ohmori H, Matsuda M, Yamaguchi I. Aging-induced decrease in the PPAR-α level in hearts is improved by exercise training.  Am J Physiol. 2002;  283 H1750-H1760
• 8 Kawamura T, Yoshida K, Sugawara A, Nagasaka M, Mori N, Takeuchi K, Kohzuki M. Regulation of skeletal muscle peroxisome proliferator-activated receptor γ expression by exercise and angiotensin-converting enzyme inhibition in fructose-fed hypertensive rats.  Hypertens Res. 2004;  27 61-70
• 9 Kimura M, Shinozaki T, Tateishi N, Yoda E, Yamauchi H, Suzuki M, Hosoyamada M, Shibasaki T. Adiponectin is regulated differently by chronic exercise than by weight-matched food restriction in hyperphagic and obese OLETF rats.  Life Sci. 2006;  79 2105-2111
• 10 Kriketos AD, Gan SK, Poynten AM, Furler SM, Chisholm DJ, Campbell LV. Exercise increases adiponectin levels and insulin sensitivity in humans.  Diabetes Care. 2004;  27 629-630
• 11 Lam TK, van de WG, Giacca A. Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites.  Am J Physiol. 2003;  284 E281-E290
• 12 Li J, Ning G, Duncan SA. Mammalian hepatocyte differentiation requires the transcription factor HNF-4alpha.  Genes Dev. 2000;  14 464-474
• 13 Moran TH, Katz LF, Plata-Salaman CR, Schwartz GJ. Disordered food intake and obesity in rats lacking cholecystokinin A receptors.  Am J Physiol. 1998;  274 R618-R625
• 14 Morifuji M, Sanbongi C, Sugiura K. Dietary soya protein intake and exercise training have an additive effect on skeletal muscle fatty acid oxidation enzyme activities and mRNA levels in rats.  Br J Nutr. 2006;  96 469-475
• 15 Muoio DM, Way JM, Tanner CJ, Winegar DA, Kliewer SA, Houmard JA, Kraus WE, Dohm GL. Peroxisome proliferator-activated receptor-alpha regulates fatty acid utilization in primary human skeletal muscle cells.  Diabetes. 2002;  51 901-909
• 16 Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in chronic disease.  Scand J Med Sci Sports. 2006;  16 S3-S63
• 17 Petridou A, Tsalouhidou S, Tsalis G, Schulz T, Michna H, Mougios V. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor γ in rat adipose tissue.  Metabolism. 2007;  56 1029-1036
• 18 Petruzzelli M, Lo Sasso G, Portincasa P, Palasciano G, Moschetta A. Targeting the liver in the metabolic syndrome: evidence from animal models.  Curr Pharm Des. 2007;  13 2199-2207
• 19 Shklyaev S, Aslanidi G, Tennant M, Prima V, Kohlbrenner E, Kroutov V, Campbell-Thompson M, Crawford J, Shek EW, Scarpace PJ, Zolotukhin S. Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats.  Proc Natl Acad Sci USA. 2003;  100 14217-14222
• 20 Steiner G, Lewis GF. Hyperinsulinemia and triglyceride-rich lipoproteins.  Diabetes. 1996;  45 (S 03) S24-S26
• 21 Tsuchida A, Yamauchi T, Takekawa S, Hada Y, Ito Y, Maki T, Kadowaki T. Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination.  Diabetes. 2005;  54 3358-3370
• 22 Walczak R, Tontonoz P. PPARadigms and PPARadoxes: expanding roles for PPARgamma in the control of lipid metabolism.  J Lipid Res. 2002;  43 177-186
• 23 Xiao DS, Ho KP, Qian ZM. Nitric oxide inhibition decreases bleomycin-detectable iron in spleen, bone marrow cells and heart but not in liver in exercise rats.  Mol Cell Biochem. 2004;  260 31-37
• 24 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.  Nature. 2003;  423 762-769
• 25 Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and apoE deficient mice from atherosclerosis.  J Biol Chem. 2003;  278 2461-2468
• 26 Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T, Ito Y, Kamon J, Tsuchida A, Kumagai K, Kozono H, Hada Y, Ogata H, Tokuyama K, Tsunoda M, Ide T, Murakami K, Awazawa M, Takamoto I, Froguel P, Hara K, Tobe K, Nagai R, Ueki K, Kadowaki T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions.  Nat Med. 2007;  13 332-339

Correspondence