Effects of PPARγ and PPARα Agonists on Serum Leptin Levels in Diet-induced Obese Rats

 

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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.

References

• 1 Flier J S. The adipocyte: storage depot or node on the energy information superhighway.  Cell. 1995;  80 15-18
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 4 Kersten S. Peroxisome proliferator activated receptors and obesity.  Eur J Pharmacol. 2002;  440 223-234
  CrossrefPubMedGoogle Scholar
• 5 Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease.  Nature. 2000;  405 421-424
  CrossrefPubMedGoogle Scholar
• 6 Knopp R H. Drug treatment of lipid disorders.  N Engl J Med. 1999;  341 498-511
  CrossrefPubMedGoogle Scholar
• 7 Lee C H, Olson P, Evans R M. Minireview: Lipid Metabolism, metabolic diseases, and peroxisome proliferator-activated receptors.  Endocrinology. 2003;  144 2201-2207
  CrossrefPubMedGoogle Scholar
• 8 Spiegelman B M. PPAR-γ: adipogenic regulator and thiazolidinedione receptor.  Diabetes. 1998;  47 507-514
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 10 Ahima R S, Flier J S. Adipose tissue as an endocrine organ.  TEM. 2000;  11 327-332
  PubMedGoogle Scholar
• 11 Considine R V. Regulation of leptin production.  Rev Endocr Metab Disord. 2001;  2 357-363
  CrossrefPubMedGoogle Scholar
• 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
  Article in Thieme ConnectPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  Article in Thieme ConnectPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  Article in Thieme ConnectPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 23 Saltiel A R, Olefsky J M. Thiazolidinediones in the treatment of insulin resistance and type II diabetes.  Diabetes. 1996;  45 1661-1669
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 28 Hardie L J, Guilhot N, Trayhurn P. Regulation of leptin production in cultured mature white adipocytes.  Horm Metab Res. 1996;  28 685-689
  PubMedGoogle Scholar
• 29 Considine R V, Caro J F. Leptin and the regulation of body weight.  Int J Biochem Cell Biol. 1997;  29 1255-1272
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar

F. B. Törüner

Gazi University Faculty of Medicine · Division of Endocrinology and Metabolism ·

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