Recent advances in the pathophysiology and pharmacological treatment of obesity

Journal of Clinical Pharmacy and Therapeutics

Volumn 37, Issue 5, 2012, Pages 525-535

  Chugh, P K ^a   Sharma, S ^a  

^a MAULANA AZAD MEDICAL COLLEGE   (India)

Author keywords

fat metabolism; food intake; obesity; overweight; thermogenesis; weight loss

Indexed keywords

AMFEBUTAMONE; AMFEBUTAMONE PLUS NALTREXONE; ANOREXIGENIC AGENT; BELORANIB; BETAHISTINE; CABERGOLINE; CETILISTAT; DEXFENFLURAMINE; FENFLURAMINE; GSK 1521498; GSK 598809; HUMAN GROWTH HORMONE[176-191][176 TYROSINE]; LEPTIN; LORCASERIN; MARAVIROC; NEUROPEPTIDE Y; OBINEPITIDE; PHENTERMINE; PHENTERMINE PLUS TOPIRAMATE; RESVERATROL; RIMONABANT; SIBUTRAMINE; TARANABANT; TESOFENSINE; TETRAHYDROLIPSTATIN; TM 30339; TM 38837; TTP 435; UNCLASSIFIED DRUG; UNINDEXED DRUG; VELNEPERIT;

ADIPOSE TISSUE; ENERGY EXPENDITURE; FOOD INTAKE; HEART INFARCTION; HUMAN; LIFESTYLE MODIFICATION; MEDLINE; OBESITY; PULMONARY HYPERTENSION; REVIEW; SATIETY; SEIZURE; STROKE; SUICIDE; THERMOGENESIS; VALVULAR HEART DISEASE; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; CLINICAL TRIALS AS TOPIC; DOUBLE-BLIND METHOD; DRUG EVALUATION, PRECLINICAL; HUMANS; OBESITY; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84865864614     PISSN: 02694727     EISSN: 13652710     Source Type: Journal    
DOI: 10.1111/j.1365-2710.2012.01347.x     Document Type: Review

References (76)

1. World Health Organisation. Media Centre Obesity and Overweight Fact Sheet N°311 Updated March 2011. 2011. Available at: http://www.who.int/ mediacentre/factsheets/fs311/en/index.html (accessed 11 July 2011).
2. Kissebah AH, Freedman DS, Peiris AN,. Health risks of obesity. Med Clin North Am, 1989; 73: 111-138. (Pubitemid 19032518)
3. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet, 2004; 363: 157-163.
4. Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes, 2004; 53: 2087-2094. (Pubitemid 38970759)
5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Executive summary of the third report of the National Cholesterol Education Program (NCEP). JAMA, 2001; 285: 2486-2497.
6. Alberti KG, Zimmet P, Shaw J,. Metabolic syndrome-a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med, 2006; 23: 469-480.
7. Gautron L, Elmquist JK,. Sixteen years and counting: an update on leptin in energy balance. J Clin Investig, 2011; 121: 2087-2093.
8. Schwartz MW, Woods SC, Porte D Jr, et al. Central nervous control of food intake. Nature, 2000; 404: 661-671. (Pubitemid 30205071)
9. Hotamisligil GS,. Inflammation and metabolic disorders. Nature, 2006; 444: 860-867. (Pubitemid 46024993)
10. Spencer M, Yao-Borengasser A, Unal R, et al. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. Am J Physiol Endocrinol Metab, 2010; 299: 1016-1027.
11. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD,. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol, 2001; 175: 81-92. (Pubitemid 32372545)
12. Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization. Front Biosci, 2008; 13: 453-461. (Pubitemid 351599757)
13. Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, 2005; 54: 2277-2286. (Pubitemid 41134253)
14. Aron-Wisnewsky J, Tordjman J, Poitou C, et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab, 2009; 94: 4619-4623.
15. Odegaard JI, Chawla A,. Alternative macrophage activation and metabolism. Annu Rev Pathol, 2011; 6: 275-297.
16. Redinger RN,. The pathophysiology of obesity and its clinical manifestations. Gastroenterol Hepatol, 2007; 3: 856-863. (Pubitemid 350305232)
17. National Institutes of Health. National Heart, Lung, and Blood Institute North American Association for the Study of Obesity. The Practical Guide Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. 2000. Obesity Education Initiative: NIH Publication Number 00-4084; October. Available at: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd-c.pdf (accessed 14 July 2011).
18. Rothman RB, Baumann MH,. Appetite suppressants, cardiac valve disease and combination pharmacotherapy. Am J Ther, 2009; 16: 354-364.
19. James WP, Caterson ID, Coutinho W, et al.; SCOUT Investigators Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363: 905-917.
20. 7TM Pharma. Obinepitide. 2011. Available at: http://www.7tm.com/R-D/ Metabolic-Disorders/Obinepitide.aspx (accessed 1 December 2011).
21. Shionogi. Press release. Shionogi Announces Positive Top Line Efficacy Results From Year-Long Studies of Velneperit, a Novel NPY Y5 Receptor Antagonist Being Investigated for the Treatment of Obesity. 2009. Osaka, Japan and Florham Park, New Jersey, USA: February 17. Available at: http://www.shionogi.co.jp/ iren/news/detail/e-090217-2.pdf (accessed 6 December 2011).
22. Clinical Trials. Double-Blind, Multi-Centre, Randomized Study to Assess the Efficacy and Safety of Velneperit (S-2367) and Orlistat Administered Individually or Combined With a Reduced Calorie Diet (RCD) in Obese Subjects. 2011. U.S. National Institutes of Health: December 8. Available at: http://clinicaltrials.gov/ct2/show/NCT01126970?term= obesity&no-unk= Y&type=Intr&rank=738 (accessed 10 December 2011).
23. 7TM Pharma. TM30339. 2011. Available at: http://www.7tm.com/R-D/ Metabolic-Disorders/TM30339.aspx (accessed 1 December 2011).
24. TransTech Pharma. TTP435. 2011. Available at: http://www.ttpharma.com/ TherapeuticAreas/MetabolicDiseases/Obesity/TTP435/tabid/126/Default.aspx (accessed 14 July 2011).
25. Aronne LJ, Tonstad S, Moreno M, et al. A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study. Int J Obes, 2010; 34: 919-935.
26. 7TM Pharma. TM38837. 2011. Available at: http://www.7tm.com/R-D/ Metabolic-Disorders/TM38837.aspx (accessed 1 December 2011).
27. Scacchi M, Pincelli AI, Cavagnini F,. Growth hormone in obesity. Int J Obes Relat Metab Disord, 1999; 23: 260-271. (Pubitemid 29118856)
28. Mekala KC, Tritos NA,. Effects of recombinant human growth hormone therapy in obesity in adults: a metaanalysis. J Clin Endocrinol Metab, 2009; 94: 130-137.
29. Nam SY, Kim KR, Cha BS, et al. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Int J Obes Relat Metab Disord, 2001; 25: 1101-1107. (Pubitemid 32721530)
30. Franco C, Brandberg J, Lonn L, et al. Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. J Clin Endocrinol Metab, 2005; 90: 1466-1474. (Pubitemid 40464006)
31. Ng FM, Sun J, Sharma L, et al. Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res, 2000; 53: 274-278. (Pubitemid 32037592)
32. Bengtsson BA, Eden S, Lonn L, et al. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab, 1993; 76: 309-317. (Pubitemid 23073047)
33. Sjödin A, Gasteyger C, Nielsen AL, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes, 2010; 34: 1634-1643.
34. Astrup A, Madsbad S, Breum L, et al. Effect of tesofensine on bodyweight loss body composition and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet, 2008; 372: 1906-1913.
35. Clinical Trials. Effects of the D3 Antagonist GSK598809 on Food Reward and Reinforcement. 2011. U.S. National Institutes of Health: December 22. Available at: http://clinicaltrials.gov/ct2/show/NCT01039454 (accessed 23 December 2011).
36. Ignar DM, Goetz AS, Noble KN, et al. Regulation of ingestive behaviors in the rat by GSK1521498, a novel micro-opioid receptor-selective inverse agonist. J Pharmacol Exp Ther, 2011; 339: 24-34.
37. Clinical Trials. A 35 Day Study to Investigate the Effects of GSK1521498 on Bodyweight in Obese Subjects With Over-Eating Behaviours. 2011. U.S. National Institutes of Health: December 7. Available at: http://clinicaltrials.gov/ct2/ show/NCT01195792?term=obesity&no-unk=Y&type=Intr&rank=241 (accessed 9 December 2011).
38. Shearman LP, Camacho RE, Sloan Stribling D, et al. Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur J Pharmacol, 2003; 475: 37-47. (Pubitemid 37088004)
39. Souers AJ, Gao J, Brune M, et al. Identification of 2-(4-benzyloxyphenyl) -N-[1- (2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl] acetamide, an orally efficacious melanin concentrating hormone receptor 1 antagonist for the treatment of obesity. J Med Chem, 2005; 48: 1318-1321. (Pubitemid 40364542)
40. Smith SR, Weissman NJ, Anderson CM, et al. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med, 2010; 363: 245-256.
41. Hurren KM, Berlie HD,. Lorcaserin: an investigational serotonin 2C agonist for weight loss. Am J Health Syst Pharm, 2011; 68: 2029-2037.
42. Anderson KA, Ribar TJ, Lin F, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab, 2008; 7: 377-388. (Pubitemid 351598022)
43. Zafgen Press Release. Zafgen Announces Positive Top Line Phase 1b Data for ZGN-433 in Obesity. 2011. Available at: http://www.zafgen.com/PDF/Zafgen-PR- 010511.pdf (accessed 9 December 2011).
44. Clinical Trials. Pharmacokinetics, Safety, Tolerability and Efficacy of Intravenous Doses of ZGN-433 in Obese Female Volunteers. 2011. U.S. National Institutes of Health: December 7. Available at: http://clinicaltrials.gov/ct2/ show/NCT01372761 (accessed 9 December 2011).
45. Smith SJ, Cases S, Jensen DR, et al. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet, 2000; 25: 87-90. (Pubitemid 30257043)
46. Clinical Trials. AZD7687 Multiple Ascending Dose Study. 2011. U.S. National Institutes of Health: December 8. Available at: http://clinicaltrials. gov/ct2/show/NCT01119352?term=obesity&no-unk=Y&type=Intr&rank=725 (accessed 10 December 2011).
47. Clinical Trials. Japanese Single and Multiple Ascending Dose, Safety, Tolerability, Pharmacokinetic (PK) & Pharmacodynamic (PD) Study of AZD7687 (JSMAD). 2011. U.S. National Institutes of Health: December 8. Available at: http://clinicaltrials.gov/ct2/show/NCT01217905?term=obesity&no-unk= Y&type=Intr&rank=1069 (accessed 10 December 2011).
48. Clinical Trials. A Multiple Dose Study Of PF-04620110 As A Modified-Release Formulation In Healthy Overweight Or Obese Subjects. 2011. U.S. National Institutes of Health: December 12. Available at: http:// clinicaltrials.gov/ct2/show/NCT01474941 (accessed 15 December 2011).
49. Amorim BS, Cintia BU, Beatriz CGF, et al. A TRbeta-selective agonist confers resistance to diet induced obesity. J Endocrinol, 2009; 203: 291-299.
50. Padwal RS, Majumdar SR,. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet, 2007; 369: 71-77. (Pubitemid 46027230)
51. Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med, 2005; 142: 532-546.
52. Torgerson JS, Hauptman J, Boldrin MN, et al. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care, 2004; 27: 155-161. (Pubitemid 38196725)
53. Bray GA, Greenway FL,. Current and potential drugs for treatment of obesity. Endocr Rev, 1999; 20: 805-875. (Pubitemid 30647075)
54. Kopelman P, Groot Gde H, Rissanen A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical). Obesity, 2010; 18: 108-115.
55. Wellcome Trust Press Release. PP1420 A Breakthrough in Appetite Suppression. 2010. Available at: http://wellcometrust.wordpress.com/2010/10/06/ pp1420 (accessed 9 December 2011).
56. Bloomgarden ZT,. Gestational diabetes mellitus and obesity. Diabetes Care, 2010; 33: e60-e65.
57. Greenway FL, Dunayevich E, Tollefson G, et al. NB-201 Study Group Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo. J Clin Endocrinol Metab, 2009; 94: 4898-4906.
58. Greenway FL, Fujioka K, Plodkowski RA, et al. COR-I Study Group Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 2010; 376: 595-605.
59. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity, 2011; 19: 110-120.
60. Gadde KM, Yonish GM, Foust MS, et al. Combination therapy of zonisamide and bupropion for weight reduction in obese women: a preliminary, randomized, open-label study. J Clin Psychiatry, 2007; 68: 1226-1229. (Pubitemid 47395625)
61. Orexigen Pharmaceuticals Inc. Press release. Orexigen ® Therapeutics Phase2b Trial for Empatic ™ Meets Primary Efficacy Endpoint Demonstrating Significantly Greater Weight Loss Versus Comparators in Obese Patients. 2009. Available at: http://ir.orexigen.com/phoenix.zhtml?c=207034&p= irolnewsArticle&ID=1336796&highlight= (accessed 9 December 2011).
62. Dunican KC, Adams NM, Desilets AR,. The role of pramlintide for weight loss. Ann Pharmacother, 2010; 44: 538-545.
63. Chan JL, Roth JD, Weyer C,. It takes two to tango: combined amylin/leptin agonism as a potential approach to obesity drug development. J Investig Med, 2009; 57: 777-783.
64. Ravussin E, Smith SR, Mitchell JA, et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity, 2009; 17: 1736-1743.
65. Clinical Trials. A Study To Examine The Efficacy And Safety Of Pramlintide+Metreleptin In Obese Subjects. 2011. U.S. National Institutes of Health: December 7. Available at: http://clinicaltrials.gov/ct2/show/ NCT01235741?term=obesity&no-unk=Y&type=Intr&rank=214 (accessed 9 December 2011).
66. Clinical Trials. To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects. 2011. U.S. National Institutes of Health: December 11. Available at: http://clinicaltrials.gov/ct2/show/NCT01420328?term= obesity&no-unk=Y&type=Intr&rank=1326 (accessed 14 December 2011).
67. Clinical Trials. Effect of Maraviroc on Metabolic Function in Obese Subjects (Phase I). 2011. U.S. National Institutes of Health: December 12. Available at: http://clinicaltrials.gov/ct2/show/NCT01133210?term= obesity&no-unk=Y&type=Intr&rank=1343 (accessed 14 December 2011).
68. Clinical Trials. Effect of Cabergoline on Weight and Glucose Tolerance. 2011. U.S. National Institutes of Health: December 12. Available at: http://clinicaltrials.gov/ct2/show/NCT01395602?term=obesity&no-unk= Y&type=Intr&rank=1363 (accessed 14 December 2011).
69. Clinical Trials. Effects of Betahistine Hydrochloride in Overweight Women. 2011. U.S. National Institutes of Health: December 12. Available at: http://clinicaltrials.gov/ct2/show/NCT00459992?term=obesity&no-unk= Y&type=Intr&rank=1189 (accessed 14 December 2011).
70. Clinical Trials. Craving, Binge Eating and Obesity. 2011. U.S. National Institutes of Health: December 8. Available at: http://clinicaltrials.gov/ct2/ show/NCT00414167?term=obesity&no-unk=Y&type=Intr&rank=617 (accessed 10 December 2011).
71. Palming J, Sjöholm K, Jernås M, et al. The expression of NAD(P)H:quinone oxidoreductase 1 is high in human adipose tissue, reduced by weight loss, and correlates with adiposity, insulin sensitivity, and markers of liver dysfunction. J Clin Endocrinol Metab, 2007; 92: 2346-2352. (Pubitemid 46997144)
72. Kim S, Jin Y, Choi Y, et al. Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol, 2011; 81: 1343-1351.
73. Timmers S, Konings E, Bilet L, et al., Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab, 2011; 14: 612-622.
74. Clinical Trials. Long-term Investigation of Resveratrol in Obesity (LIRMOI). 2011. U.S. National Institutes of Health: December 8. Available at: http://clinicaltrials.gov/ct2/show/NCT00414167?term=obesity&no-unk= Y&type=Intr&rank=617 (accessed 10 December 2011).
75. Clinical Trials. Long-term Investigation of Resveratrol on Fat Metabolism in Obese Men. 2011. U.S. National Institutes of Health: December 7. Available at: http://clinicaltrials.gov/ct2/show/NCT01446276?term=obesity&no-unk= Y&type=Intr&rank=410 (accessed 9 December 2011).
76. Clinical Trials. Resveratrol in Type2 Diabetes and Obesity. 2011. U.S. National Institutes of Health: December 7. Available at: http://clinicaltrials. gov/ct2/show/NCT01158417?term=obesity&no-unk=Y&type=Intr&rank=202 (accessed 9 December 2011).