Obesity is one of the serious problems of the 21st century and affects nearly 300 million people worldwide. About 13% of the world’s adult population and over 41 million children under the age of 5 were overweight or obese. It is believed that the common cause of obesity is due to the imbalance in the homeostatic and hedonic regulation and improper disposition of energy intake due to decrease in physical activity. Recent advances in neurobiology have greatly enhanced our understanding of the neuronal and peripheral factors involved in eating behaviour; for an overview of the functional organization of feeding circuits. The Food and Drug Administration (FDA) has approved five long-term obesity drugs for adults who are obese so far: lorcaserin, phentermine/ topiramate, naltrexone/bupropion, Orlistat and liraglutide over the past few years. There is an inadequacy in the selection of accurate animal models and methods to validate the toxicity of drugs to treat obesity. To tackle the growing obesity epidemic and its associated metabolic disorders, there is an urgent need to further decipher the CNS-level molecular mechanisms that lead to the dysregulation in energy homeostasis. This review explains the novel methods which might be the promising tools in the management of obesity in future.
Cite this article:
V. Chitra , Rini. R. Neuro Pharmacological Review on Obesity. Research J. Pharm. and Tech 2020; 13(3):1549-1554. doi: 10.5958/0974-360X.2020.00281.4
1. C.W. Smith William Thomson and the creation of thermodynamics: 1840–1855, Arch Hist Exact Sci, 16 (3) (1977), pp. 231-288
2. W.F. Boron, E.L. Boulpaep (Eds.), Medical physiology (3rd ed.), Elsevier, Philadelphia, PA (2017), p. Xii [1297 pages]
3. S.M. GrundyMetabolic complications of obesity, Endocrine, 13 (2) (2000), pp. 155-165
4. K.G. Alberti, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity, Circulation, 120 (16) (2009), pp. 1640-1645
5. Collaboration, N.C.D.R.F Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults, Lancet, 390 (10113) (2017), pp. 2627-2642
6. Fact sheet obesity and overweight 03-01-2016; Available from: http://www.who.int/mediacentre/factsheets/fs311/en/# (2016)
7. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA. 2016;315(21):2284–2291.
8. Liu X, Chen Y, Boucher NL, Rothberg AE. Prevalence and change of central obesity among US Asian adults: NHANES 2011–2014. BMC Public Health. 2017;17(1):678.
9. St-Onge MP. Sleep-obesity relation: underlying mechanisms and consequences for treatment. Obesity Reviews. 2017;18(suppl 1):34–39.
10. Hirshkowitz M, Whiton K, Albert SA, et al. National Sleep Foundation’s updated sleep duration recommendations: final report. Sleep Health. 2015;1(4):233–243.
11. K.E. Koopman, et al., Diet-induced changes in the Lean Brain: hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region, Mol Metab, 2 (4) (2013), pp. 417-422
12. R.I. Versteeg, et al., Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding, FASEB J, 31 (10) (2017), pp. 4545-4554
13. E.M. van der Zwaal, et al., Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss, EurNeuropsychopharmacol, 26 (7) (2016), pp. 1190-1200
14. D.D. Lam, et al. Brain serotonin system in the coordination of food intake and body weight, PharmacolBiochemBehav, 97 (1) (2010), pp. 84-91
15. J.C. Halford, et al.Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity, Curr Drug Targets, 6 (2) (2005), pp. 201-213
16. M.M. Meguid, et al. Hypothalamic dopamine and serotonin in the regulation of food intake Nutrition, 16 (10) (2000), pp. 843-857
17. S.E. la Fleur, M.J. Serlie. The interaction between nutrition and the brain and its consequences for body weight gain and metabolism; studies in rodents and men Best Pract Res Clin Endocrinol Metab, 28 (5) (2014), pp. 649-659
18. K.A. van Galen, et al., The role of central dopamine and serotonin in human obesity: lessons learned from molecular neuroimaging studies Metabolism, 85 (2018), pp. 325-339
19. E.A. Bohula, et al., Cardiovascular safety of lorcaserin in overweight or obese patients, N Engl J Med, 20 (12) (2018), p. 379
20. K. Blum, P.K. Thanos, M.S. Gold- Dopamine and glucose, obesity, and reward deficiency syndrome, Front Psychol, 5 (2014), p. 919
21. A.J. Tulloch, et al. Neural responses to macronutrients: hedonic and homeostatic mechanisms, Gastroenterology, 148 (6) (2015), pp. 1205-1218
22. P.J. Kenny. Reward mechanisms in obesity: new insights and future directions, Neuron, 69 (4) (2011), pp. 664-679
23. P.M. Johnson, P.J. Kenny. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats, Nat Neurosci, 13 (5) (2010), pp. 635-641
24. B.S. Gluskin, B.J. Mickey. Genetic variation and dopamine D2 receptor availability: A systematic review and meta-analysis of human in vivo molecular imaging studies, Transl Psychiatry, 6 (2016), Article e747
25. E.P. Noble, et al. D2 dopamine receptor gene and obesity, Int J Eat Disord, 15 (3) (1994), pp. 205-217
26. E. Stice, et al. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele Science, 322 (5900) (2008), pp. 449-452
27. D.M. Small, M. Jones-Gotman, A. DagherFeeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers, Neuroimage, 19 (4) (2003), pp. 1709-1715
28. G.J. Wang, et al. BMI modulates calorie-dependent dopamine changes in accumbens from glucose intake, PLoS One, 9 (7) (2014), Article e101585
29. C. Szalay, et al. Gustatory perception alterations in obesity: an fMRI study, Brain Res, 1473 (2012), pp. 131-140
30. Y. Rothemund, et al. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals, Neuroimage, 37 (2) (2007), pp. 410-421
31. L.E. Stoeckel, et al. Widespread reward-system activation in obese women in response to pictures of high-calorie foods, Neuroimage, 41 (2) (2008), pp. 636-647
32. L.0E. Stoeckel, et al. Effective connectivity of a reward network in obese women, Brain Res Bull, 79 (6) (2009), pp. 388-395
33. W. Scharmuller, et al. Appetite regulation during food cue exposure: a comparison of normal-weight and obese women, NeurosciLett, 518 (2) (2012), pp. 106-110
34. A.M. Jastreboff, et al. Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels, Diabetes Care, 36 (2) (2013), pp. 394-402
35. Londoño-Lemos ME (2012) Pharmacological treatment against obesity. Rev Colomb Cienc Quim Farm 41: 217-261.
36. Sobrino Crespo C, Perianes Cachero A, Puebla Jiménez L, Barrios V, Arilla Ferreiro E (2014) Peptides and food intake. Front Endocrinol5: 58.
37. Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, et al. (2013) Leptin at the intersection of neuroendocrinology and metabolism: Current evidence and therapeutic perspectives. Cell Metab 18: 29-42.
38. Kotz C, Nixon J, Butterick T, Perez-Leighton C, Teske J, et al. (2012) Brain orexin promotes obesity resistance. Ann N Y AcadSci 1264: 72-86.
39. Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 2013;27:234-50.
40. Nedergaard J, Golozoubova V, Matthias A, et al. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. BiochimBiophys Acta 2001;1504:82-106.
41. Cohen P, Spiegelman BM. Cell biology of fat storage. Mol Biol Cell 2016;27:2523-7.
42. Vargas-Castillo A, Fuentes-Romero R, Rodriguez-Lopez LA, et al. Understanding the Biology of Thermogenic Fat: Is Browning A New Approach to the Treatment of Obesity? Arch Med Res 2017;48:401-413.
43. Wang S, Liang X, Yang Q, et al. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) alpha1. Int J Obes (Lond) 2015;39:967-76.
44. Baskaran P, Krishnan V, Ren J, et al. Capsaicin induces browning of white adipose 600 tissue and counters obesity by activating TRPV1 channel-dependent mechanisms. Br J 601 Pharmacol 2016;173:2369-89.
45. Mercader J, Ribot J, Murano I, et al. Remodeling of white adipose tissue after retinoic 603 acid administration in mice. Endocrinology 2006;147:5325-32.
46. Matta JA, Miyares RL, Ahern GP. TRPV1 is a novel target for omega-3 polyunsaturated fatty acids. J Physiol 2007;578:397-411.
47. Quesada-Lopez T, Cereijo R, Turatsinze JV, et al. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes. Nat Commun 2016; 7:13479.
48. Cho S, Namkoong K, Shin M, et al. Cardiovascular Protective Effects and Clinical Applications of Resveratrol. J Med Food 2017;20:323-334.
49. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013;368:1685-94.
50. Hoffstedt J FD, Löfgren P. Impaired subcutaneous adipocyte lipogenesis is associated with systemic insulin resistance and increased apolipoprotein B/AI ratio in men and women.. J Intern Med. 2007;262:131-9. 639
51. Collet TH, Dubern B, Mokrosinski J, et al. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Mol Metab 2017;6:1321-1329.
52. Blevins JE, Baskin DG. Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans. PhysiolBehav 2015;152:438-49.
53. Blevins JE, Graham JL, Morton GJ, et al. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. Am J PhysiolRegulIntegr Comp Physiol 2015;308:R431-8.
54. Tribollet E, Barberis C, Dubois-Dauphin M, et al. Localization and characterization of binding sites for vasopressin and oxytocin in the brain of the guinea pig. Brain Res 1992;589:15-23.
55. Ott V, Finlayson G, Lehnert H, et al. Oxytocin reduces reward-driven food intake in humans. Diabetes 2013;62:3418-25.
56. Prashant S Mewada, Chirag K Patel, CS Rami, HU Patel, CN Patel. New Emerging Targets for Obesity. Asian J. Research Chem. 3(2): April- June 2010; Page 278-287.
57. Meenakshi Mohan. The Role of Leptin on Obesity: A Review. Research J. Pharm. and Tech. 7(12): Dec. 2014; Page 1501-1505.
58. R. Monalisa. Role of Leptin in obesity. Research J. Pharm. and Tech. 8(8): August, 2015; Page 1073-1076.
59. B. Reshmi, Gowri Sethu. A Study on Obesity among Children. Research J. Pharm. and Tech. 8(8): August, 2015; Page 1177-1178.
60. Aniruddh Menon, M.S.Thenmozhi. Correlation Between Thyroid Function and Obesity. Research J. Pharm. and Tech 2016; 9(10):1568-1570.
61. Ahmed Hilal Sheriff K, Karpagam Krishnamoorthy. Satiety Centre of The Brain –A boon or A curse?. Research J. Pharm. and Tech. 2017; 10(4): 963-967.
62. P. Shanmugasundaram, T. N. Uma Maheshwari, Praveen. D, A. Harini. A Comprehensive Review on natural ways to Lose Weight. Research J. Pharm. and Tech 2017; 10(11): 4030-4032.
63. Shovit Ranjan, Praveen Kumar Sharma. Association of Brain-Derived Neurotrophic factor (BDNF) gene SNP G196A with Type 2 Diabetes and Obesity: A Meta- Analysis. Research J. Pharm. and Tech 2017; 10(12): 4297-4305.
64. Doaa Mahdi Omran, Saad Merza Alaraji, Ali Hussein Albayati, Wathiq Essam. Relationship between Ghrelin and Leptin with Insulin Resistance in Obese Patients and Non-Obese Individuals. Research J. Pharm. and Tech. 2018; 11(1): 281-283.
65. Amean A. Yasir. Assessment of Family Lifestyle and Eating Habits for Home Prevention in Hilla City. Research J. Pharm. and Tech 2018; 11(5):1847-1850.