Partha Sarathi Bairy



 Day-by-day metabolic disorder/syndrome (MS) falling in love with current lifestyle status of everyone especially after study age group of people. If we look carefully around us, we will see evidence is growing up of diabetic, obese, and hypertensive population regularly. In urgencies of above view extensive literature survey has been done prioritizing prevalence of metabolic disorder and peroxisome proliferator-activated receptor-gamma (PPAR-γ) as potential target protein. This review covered current status of MS emphasizing diabetes along with its management criteria. Special importance is given to PPAR-γ exploring its metabolic regulation and structural orientation for understanding ligand-protein interaction. Development of PPAR-γ agonist thiazolidinediones (TZDs) and other pharmacodynamic importance of this nuclear receptor also discussed. Being as nuclear receptor more genomics exploitation needs to be done emphasizing minimization of cardiac adverse effect. Selective PPAR modulator (SPPRM), TZDs are the master regulator of adipogenesis and angiogenesis which makes TZD more interesting topic to explore. Developmental hierarchy suggests that in a few years from now PPAR-γ won’t be in the list of double edge sword.


Metabolic disorder, Diabetes, Peroxisome proliferator-activated receptor-γ, Retinoid X receptor, Thiazolidinedione, Dyslipidemia.

| PDF |


Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: A comprehensive review. J Clin Endocrinol Metab 2009;94(6):1853-78.

Pradeepa R, Surendar J, Indulekha K, Chella S, Anjana RM, Mohan V. Prevalence of metabolic syndrome and its association with coronary artery disease among an Urban Elderly South Indian population (CURES- 145). J Assoc Physicians India 2016;64(5):20-5.

Prasad DS, Kabir Z, Dash AK, Das BC. Prevalence and risk factors for metabolic syndrome in Asian Indians: A community study from urban Eastern India. J Cardiovasc Dis Res 2012;3(3):204-11.

Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA 2015;313(19):1973-4.

Misra A, Khurana L. The metabolic syndrome in South Asians: Epidemiology, determinants, and prevention. Metab Syndr Relat Disord 2009;7(6):497-514.

Ravikiran M, Bhansali A, Ravikumar P, Bhansali S, Dutta P, Thakur JS, et al. Prevalence and risk factors of metabolic syndrome among Asian Indians: A community survey. Diabetes Res Clin Pract 2010;89(2):181-8.

Bairy PS, Shankar B, Das A. Diabetes mellitus and antidiabetics with reference to alpha glucosidase inhibitors. J Biomed Pharm Res 2015;4(6):10-6.

American Diabetes Association. Statistics about Diabetes. Available from: [Last updated on June 17].

WHO. WHO Library Cataloguing-in-Publication Data, Global Report on Diabetes. Geneva: World Health Organization; 2016.

Roglic G. WHO Global report on diabetes: A summary. Int J Noncommun Dis 2016;1:3-8.

Dussa K, Parimalakrishnan S, Sahay R. Assessment of diabetes knowledge using diabetes knowledge questionnaire among people with Type 2 diabetes mellitus. Asian J Pharm Clin Res 2015;8(2):254-6.

Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPAR γ): A review. Biochem Pharmacol 2014;92:73-89.

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112(17):2735-52.

Fappa E, Yannakoulia M, Pitsavos C, Skoumas I, Valourdou S, Stefanadis C. Lifestyle intervention in the management of metabolic syndrome: Could we improve adherence issues? Nutrition 2008;24(3):286-91.

Peter JS, Sabina EP. Global current trends in natural products for diabetes management: A review. Int J Pharm Pharm Sci 2016;8(4):20-8.

Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2004;89(6):2595-600.

Mallappa RH, Rokana N, Duary RK, Panwar H, Batish VK, Grover S. Management of metabolic syndrome through probiotic and prebiotic interventions. Indian J Endocrinol Metab 2012;16(1):20-7.

Bairy PS, Das A, Nainwal LM, Mohanta TK, Kumawat MK, Mohapatra PK, et al. Design, synthesis and anti-diabetic activity of some novel xanthone derivatives targeting α-glucosidase. Bangladesh J Pharmacol 2016;11:308-18.

Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications-a review. Nutr J 2014;13:17.

Miller BR, Nguyen H, Hu CJ, Lin C, Nguyen QT. New and emerging drugs and targets for Type 2 diabetes: Reviewing the evidence. Am Health Drug Benefits 2014;7(8):452-63.

Asche C, LaFleur J, Conner C. A review of diabetes treatment adherence and the association with clinical and economic outcomes. Clin Ther 2011;33(1):74-109.

Russo GL, Russo M, Ungaro P. AMP-activated protein kinase: A target for old drugs against diabetes and cancer. Biochem Pharmacol 2013;86(3):339-50.

Overton HA, Fyfe MC, Reynet C. GPR119, a novel G protein-coupled receptor target for the treatment of Type 2 diabetes and obesity. Br J Pharmacol 2008;153 Suppl 1:S76-81.

Latruffe N, Vamecq J. Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism. Biochimie 1997;79(2-3):81-94.

Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBP alpha induces adipogenesis through PPAR gamma: A unified pathway. Genes Dev 2002;16(1):22-6.

Lewis SN, Garcia Z, Hontecillas R, Bassaganya-Riera J, Bevan DR. Pharmacophore modeling improves virtual screening for novel peroxisome proliferator-activated receptor-gamma ligands. J Comput Aided Mol Des 2015;29(5):421-39.

Stanley TB, Leesnitzer LM, Montana VG, Galardi CM, Lambert MH, Holt JA, et al. Subtype specific effects of peroxisome proliferator-activated receptor ligands on corepressor affinity. Biochemistry 2003;42(31):9278-87.

de Groot JC, Weidner C, Krausze J, Kawamoto K, Schroeder FC, Sauer S, et al. Structural characterization of amorfrutins bound to the peroxisome proliferator-activated receptor γ. J Med Chem 2013;56(6):1535-43.

Veeramachaneni GK, Raj KK, Bondili JS, Talluri VR. Screening and molecular docking studies of new natural agonists against peroxisome proliferator-activated receptor-alpha targeted to treat obesity. Asian J Pharm Clin Res 2016;9(4):80-4.

Semple RK, Chatterjee VK, O’Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest 2006;116(3):581-9.

Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: No alteration in adipose tissue of obese and NIDDM patients. Diabetes 1997;46(8):1319-27.

Fruchart JC. Peroxisome proliferator-activated receptor-alpha (PPARalpha): At the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 2009;205(1):1-8.

Barish GD, Narkar VA, Evans RM. PPAR delta: A dagger in the heart of the metabolic syndrome. J Clin Invest 2006;116(3):590-7.

Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med 2004;10(4):355-61.

Luquet S, Gaudel C, Holst D, Jehl-Pietri C, Fredenrich A. Grimaldi PA. Roles of PPAR delta in lipid absorption and metabolism: A new target for the treatment of Type 2 diabetes. Biochim Biophys Acta 2005;1740(2):313-7.

Kaserer T, Obermoser V, Weninger A, Gust R, Schuster D. Evaluation of selected 3D virtual screening tools for the prospective identification of peroxisome proliferator-activated receptor (PPAR) γ partial agonists. Eur J Med Chem 2016;124:49-62.

Tenenbaum A, Motro M, Fisman EZ. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: The bezafibrate lessons. Cardiovasc Diabetol 2005;4:14.

Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, et al. The protein data bank. Acta Crystallogr D Biol Crystallogr 2002;58:899-907.

Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris TP, et al. Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature 2008;456(7220):350-6.

Zoete V, Grosdidier A, Michielin O. Peroxisome proliferator-activated receptor structures: Ligand specificity, molecular switch and interactions with regulators. Biochim Biophys Acta 2007;1771(8):915-25.

Salam NK, Huang TH, Kota BP, Kim MS, Li Y, Hibbs DE. Novel PPAR-gamma agonists identified from a natural product library: A virtual screening, induced-fit docking and biological assay study. Chem Biol Drug Des 2008;71(1):57-70.

Datar AP, Aher SB. Design and synthesis of novel thiazolidine-2,4-diones as hypoglycemic agents. J Saudi Chem Soc 2016;20:196-201.

Begum A, Begum S, Prasad KV, Bharathi K. In silico studies on functionalized azaglycine derivatives containing 2, 4-thiazolidinedione scaffold on multiple targets. Int J Pharm Pharm Sci 2017;9(8):209-15.

Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995;270(22):12953-6.

Frias JP, Yu JG, Kruszynska YT, Olefsky JM. Metabolic effects of troglitazone therapy in Type 2 diabetic, obese, and lean normal subjects. Diabetes Care 2000;23(1):64-9.

Scheen AJ. Thiazolidinediones and liver toxicity. Diabetes Metab 2001;27(3):305-13.

Berlie HD, Kalus JS, Jaber LA. Thiazolidinediones and the risk of edema: A meta-analysis. Diabetes Res Clin Pract 2007;76(2):279-89.

Isley WL. Hepatotoxicity of thiazolidinediones. Expert Opin Drug Saf 2003;2(6):581-6.

Villacorta L, Schopfer FJ, Zhang J, Freeman BA, Chen YE. PPAR-γ and its ligands: Therapeutic implications in cardiovascular disease. Clin Sci (Lond) 2009;116(3):205-18.

Agrawal R, Jain P, Dikshit SN. Balaglitazone: A second generation peroxisome proliferator-activated receptor (PPAR) gamma (γ) agonist. Mini Rev Med Chem 2012;12(2):87-97.

Guasch L, Sala E, Valls C, Blay M, Mulero M, Arola L, et al. Structural insights for the design of new PPARgamma partial agonists with high binding affinity and low transactivation activity. J Comput Aided Mol Des 2011;25(8):717-28.

Wojtowicz AK, Szychowski KA, Kajta M. PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells. Neurotox Res 2014;25(3):311-22.

dos Santos JC, Bernardes A, Giampietro L, Ammazzalorso A, De Filippis B, Amoroso R, et al. Different binding and recognition modes of GL479, a dual agonist of peroxisome proliferator-activated receptor α/γ. J Struct Biol 2015;191(3):332-40.

Gross B, Staels B. PPAR agonists: Multimodal drugs for the treatment of Type-2 diabetes. Best Pract Res Clin Endocrinol Metab 2007;21(4):687-710.

Zheng W, Qiu L, Wang R, Feng X, Han Y, Zhu Y, et al. Selective targeting of PPAR? By the natural product chelerythrine with a unique binding mode and improved antidiabetic potency. Sci Rep 2015;5:12222.

Sauer S. Amorfrutins: A promising class of natural products that are beneficial to health. Chembiochem 2014;15(9):1231-8.

Ye J. Challenges in drug discovery for thiazolidinedione substitute. Yao Xue Xue Bao 2011;1(3):137-42.

Grommes C, Landreth GE, Schlegel U, Heneka MT. The non-thiazolidinedione tyrosine-based peroxisome proliferator-activated receptor gamma ligand GW7845 induces apoptosis and limits migration and invasion of rat and human glioma cells. J Pharmacol Exp Ther


Stienstra R, Duval C, Müller M, Kersten S. PPARs, obesity, and Inflammation. PPAR Res 2007;2007:95974.

Yoshimura R, Matsuyama M, Hase T, Tsuchida K, Kuratsukuri K, Kawahito Y, et al. The effect of peroxisome proliferator-activated receptor-gamma ligand on urological cancer cells. Int J Mol Med 2003;12(6):861-5.

Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011;2(4):236-40.

Grommes C, Landreth GE, Heneka MT. Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol 2004;5(7):419-29.

Sikka S, Chen L, Sethi G, Kumar AP. Targeting PPARγ Signaling cascade for the prevention and treatment of prostate cancer. PPAR Res 2012;2012:968040.

Boris M, Kaiser CC, Goldblatt A, Elice MW, Edelson SM, Adams JB, et al. Effect of pioglitazone treatment on behavioral symptoms in autistic children. J Neuroinflammation 2007;4:3.

Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355(22):2297-307.

Shah DK, Menon KM, Cabrera LM, Vahratian A, Kavoussi SK, Lebovic DI. Thiazolidinediones decrease vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells in vitro. Fertil Steril 2010;93(6):2042-7.

About this article




Metabolic disorder, Diabetes, Peroxisome proliferator-activated receptor-γ, Retinoid X receptor, Thiazolidinedione, Dyslipidemia.





Additional Links

Manuscript Submission


Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 12 December 2017 Page: 40-44

Print ISSN


Online ISSN


Authors & Affiliations

Partha Sarathi Bairy
Department of Pharmaceutical Sciences, SBSPGI, Balawala, Dehradun, Uttarakhand-248161. India

Article Tools

Email this article (Login required)
Email the author (Login required)


  • There are currently no refbacks.