Subscribe to RSS
DOI: 10.1055/s-2004-814452
Effects of PPARγ and PPARα Agonists on Serum Leptin Levels in Diet-induced Obese Rats
Publication History
Received 23 July 2003
Accepted after Revision 5 January 2004
Publication Date:
28 April 2004 (online)
![](https://www.thieme-connect.de/media/hmr/200404/lookinside/thumbnails/10.1055-s-2004-814452-1.jpg)
Abstract
Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARγ agonists decrease leptin levels. However, the effects of PPARα agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARγ agonist rosiglitazone (RSG) and PPARα agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 ± 19 vs. 207 ± 34 mg/dl, 58 ± 20 vs. 112 ± 23 mg/dl, 3.1 ± 1.0 vs. 15.2 ± 4.0 ng/ml, 1.6 ± 0.5 vs. 3.6 ± 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 ± 19 vs. 207 ± 34 mg/dl, 57 ± 16 vs. 112 ± 23 mg/dl, 4.3 ± 2.1 vs. 15.2 ± 4.0 ng/ml, 1.6 ± 0.4 vs. 3.6 ± 1.6 ng/ml, respectively). These results suggest that PPARα agonists may decrease serum glucose, insulin and leptin levels as PPARγ agonists do in diet-induced obese rats.
Key words
Diet-induced obesity - Leptin - Rosiglitazone - Gemfibrozil - PPAR
References
- 1 Flier J S. The adipocyte: storage depot or node on the energy information superhighway. Cell. 1995; 80 15-18
- 2 Must A, Spadano J, Coakley E H, Field A E, Colditz G, Dietz W H. The disease burden associated with overweight and obesity. JAMA. 1999; 282 1523-1529
- 3 Markovic T P, Jenkins A B, Campbell L V, Furler S M, Kraegen E W, Chisholm D J. The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM. Diabetes Care. 1998; 21 687-694
- 4 Kersten S. Peroxisome proliferator activated receptors and obesity. Eur J Pharmacol. 2002; 440 223-234
- 5 Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000; 405 421-424
- 6 Knopp R H. Drug treatment of lipid disorders. N Engl J Med. 1999; 341 498-511
- 7 Lee C H, Olson P, Evans R M. Minireview: Lipid Metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology. 2003; 144 2201-2207
- 8 Spiegelman B M. PPAR-γ: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998; 47 507-514
- 9 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse gene and its human homologue. Nature. 1994; 372 425-432
- 10 Ahima R S, Flier J S. Adipose tissue as an endocrine organ. TEM. 2000; 11 327-332
- 11 Considine R V. Regulation of leptin production. Rev Endocr Metab Disord. 2001; 2 357-363
- 12 Walker C G, Bryson J M, Phuyal J L, Caterson I D. Dietary modulation of circulating leptin levels: site-spesific changes in fat deposition and ob mRNA expression. Horm Metab Res. 2001; 34 176-181
- 13 Akiyama T, Tachibana I, Shirohara H, Watanabe N, Otsuki M. High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat. Diabetes Res Clin Pract. 1996; 31 27-35
- 14 Storlien L H, James D E, Burleigh K M, Chisholm D J, Kraegen E W. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol. 1986; 251 E576-E583
- 15 Johansen T, Richelsen B, Hansen H S, Din N, Malmlöf K. Growth hormone-mediated breakdown of body fat: effects of GH on lipases in adipose tissue and skeletal muscle of old rats fed different diets. Horm Metab Res. 2003; 35 243-250
- 16 Masuzaki H, Ogawa Y, Hosoda K, Kawada T, Fushiki T, Nakao K. Augmented expression of the obese gene in the adipose tissue from rats fed high-fat diet. Biochem Biophys Res Commun. 1995; 216 355-358
- 17 Ainslie D A, Proietto J, Fam B C, Thorburn A W. Short-term, high-fat diets lower circulating leptin concentrations in rats. Am J Clin Nutr. 2000; 71 438-442
- 18 Takahashi N, Patel H R, Qi Y, Dushay J, Ahima R S. Divergent effects of leptin in mice susceptible or resistant to obesity. Horm Metab Res. 2002; 34 691-697
- 19 Pickavance L C, Tadayyon M, Widdowson P S, Buckingham R E, Wilding J PH. Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution. Br J Pharmacology. 1999; 128 1570-1576
- 20 Hevener A, Reichart D, Janez A, Olefsky J. Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance in male wistar rats. Diabetes. 2001; 50 2316-2322
- 21 Oakes N D, Camilleri S, Furler S M, Chisholm D J, Kraegen E W. The insulin sensitizer, BRL 49 653, reduces systemic fatty acid supply and utilization and tissue lipid availability in the rat. Metabolism. 1997; 46 935-942
- 22 Kraegen E W, Cooney G J, Ye J, Thompson A L. Triglycerides, fatty acids and insulin resistance - hyperinsulinemia. Exp Clin Endocrinol Diabetes. 2001; 109 S516-S526
- 23 Saltiel A R, Olefsky J M. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996; 45 1661-1669
- 24 De Vos P, Lefebvre A M, Miller S G, Guerro-Millo M, Wong K, Saladin R, Hamann L G, Staels B, Briggs M R, Auwerx J. Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated reseptor γ. J Clin Invest. 1996; 98 1004-1009
- 25 Wang Q, Dryden S, Frankish H M, Bing C, Pickavance L, Hopkins D, Buckingham R, Williams G. Increased feeding in fatty Zucker rats by the thiazolidinedione BRL 49 653 (rosiglitazone) and the possible involvement of leptin and hypothalamic neuropeptide Y. Br J Pharmacology. 1997; 122 1405-1410
- 26 Kallen C B, Lazar M A. Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc Natl Acad Sci USA. 1996; 93 5793-5796
- 27 Hollenberg A N, Susulic V S, Madura J P, Zhang B, Moller D E, Tontonoz P, Sarraf P, Spiegelman B M, Lowell B B. Functional antagonism between CCAAT/enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma on the leptin promoter. J Biol Chem. 1997; 272 5283-5290
- 28 Hardie L J, Guilhot N, Trayhurn P. Regulation of leptin production in cultured mature white adipocytes. Horm Metab Res. 1996; 28 685-689
- 29 Considine R V, Caro J F. Leptin and the regulation of body weight. Int J Biochem Cell Biol. 1997; 29 1255-1272
- 30 Chaput E, Saladin R, Silvestre M, Edgar A D. Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun. 2000; 271 445-450
- 31 Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, Herbert J M, Winegar D A, Willson T M, Fruchart J C, Berge R K, Staels B. Peroxisome proliferator-activated receptor α activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000; 275 16638-16642
- 32 Mancini F P, Lanni A, Sabatino L, Moreno M, Giannino A, Contaldo F, Colantuoni V, Goglia F. Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats. FEBS Lett. 2001; 491 154-158
- 33 Kochan Z, Karbowska J, Swierczynski J. Effect of clofibrate on malic enzyme and leptin mRNAs level in rat brown and white adipose tissue. Horm Metab Res. 1999; 31 538-542
- 34 Rizvi F, Puri A, Bhatia G, Khanna A K, Wulff E M, Rastogi A K, Chander R. Antidyslipidemic action of fenofibrate in dyslipidemic-diabetic hamster model. Biochem Biophys Res Commun. 2003; 305 215-222
- 35 Ye J M, Doyle P, Iglesias M A, Watson D G, Cooney G J, Kraegen E. Peroxisome proliferator-activated receptor (PPAR)-α activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats. Diabetes. 2001; 50 411-417
F. B. Törüner
Gazi University Faculty of Medicine · Division of Endocrinology and Metabolism ·
Halit Ziya Sokak 24/8 Çankaya · 06540 · Ankara · Turkey
Phone: +90(312)214-1000, -5804 ·
Fax: +90(312)2154204
Email: fusunbalostoruner@yahoo.com