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A review of the neurobiology of obesity and the available pharmacotherapies

Published online by Cambridge University Press:  19 January 2018

Mehala Subramaniapillai
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
Roger S. McIntyre*
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Ontario, Ontario, Canada
*Address for correspondence: Roger S. McIntyre, MD, FRCPC, Professor of Psychiatry and Pharmacology, University of Toronto, Head, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, MP 9-325, Toronto, ON M5T 2S8, Canada. (Email:


Obesity is becoming an increasing problem worldwide. In addition to causing many physical health consequences, there is increasing evidence demonstrating that obesity is toxic to the brain and, as such, can be considered a disease of the central nervous system. Peripheral level regulators of appetite, such as leptin, insulin, ghrelin, and cholecystokinin, feed into the appetite center of the brain, which is controlled by the hypothalamus, to maintain homeostasis and energy balance. However, food consumption is not solely mediated by energy balance, but is also regulated by the mesolimbic reward system, where motivation, reward, and reinforcement factors influence obesity. The purpose of this review is to highlight the neurobiology of eating behavior and obesity and to describe various neurobiological treatment mechanisms to treat obesity.

CME Review Article
© Cambridge University Press 2018 

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This activity is supported by an unrestricted educational grant from Orexigen Therapeutics.


1. Vucetic, Z, Reyes, TM. Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity. Wiley Interdiscip Rev Syst Biol Med. 2010; 2(5): 577593.Google Scholar
2. GBD 2015 Obesity Collaborators, Afshin, A, Forouzanfar, MH, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017; 377(1): 1327.Google Scholar
3. Singh, GM, Danaei, G, Farzadfar, F, et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One. 2013; 8(7): e65174.CrossRefGoogle ScholarPubMed
4. Lauby-Secretan, B, Scoccianti, C, Loomis, D, et al. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016; 375(8): 794798.Google Scholar
5. McIntyre, RS, Mansur, RB, Lee, Y, et al. Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: results from the global mood and brain science initiative. Bipolar Disord. 2017; 19(2): 128134.Google Scholar
6. Mansur, RB, McIntyre, RS, Cao, B, et al. Obesity and frontal-striatal brain structures in offspring of individuals with bipolar disorder: results from the global mood and brain science initiative. Bipolar Disord. In press. doi: 10.1111/bdi.12559.CrossRefGoogle Scholar
7. Rajan, TM, Menon, V. Psychiatric disorders and obesity: a review of association studies. J Postgrad Med. 2017; 63(3): 182190.Google Scholar
8. Anis, AH, Zhang, W, Bansback, N, Guh, DP, Amarsi, Z, Birmingham, CL. Obesity and overweight in Canada: an updated cost-of-illness study. Obes Rev. 2010; 11(1): 3140.Google Scholar
9. Swinburn, BA, Sacks, G, Hall, KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011; 378(9793): 804814.Google Scholar
10. Mishra, AK, Dubey, V, Ghosh, AR. Obesity: an overview of possible role(s) of gut hormones, lipid sensing and gut microbiota. Metabolism. 2016; 65(1): 4865.Google Scholar
11. Elmquist, JK, Elias, CF, Saper, CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 1999; 22(2): 221232.CrossRefGoogle ScholarPubMed
12. Krügel, U, Schraft, T, Kittner, H, Kiess, W, Illes, P. Basal and feeding-evoked dopamine release in the rat nucleus accumbens is depressed by leptin. Eur J Pharmacol. 2003; 482(1–3): 185187.Google Scholar
13. Woods, SC, D’Alessio, DA. Central control of body weight and appetite. J Clin Endocrinol Metab. 2008; 93(11 Suppl 1): S3750.CrossRefGoogle ScholarPubMed
14. Abizaid, A, Liu, ZW, Andrews, ZB, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006; 116(12): 32293239.Google Scholar
15. Egecioglu, E, Jerlhag, E, Salomé, N, et al. Ghrelin increases intake of rewarding food in rodents. Addict Biol. 2010; 15(3): 304311.CrossRefGoogle ScholarPubMed
16. Choi, DL, Davis, JF, Fitzgerald, ME, Benoit, SC. The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats. Neuroscience. 2010; 167(1): 1120.Google Scholar
17. Narita, M, Nagumo, Y, Hashimoto, S, et al. Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. J Neurosci. 2006; 26(2): 398405.Google Scholar
18. Lean, MEJ, Malkova, D. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence? Int J Obes (Lond). 2016; 40(4): 622632.Google Scholar
19. Millington, GWM. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab (Lond). 2007; 4: 18.Google Scholar
20. Dhillo, WS. Appetite regulation: an overview. Thyroid. 2007; 17(5): 433445.Google Scholar
21. Grosshans, M, Loeber, S, Kiefer, F. Implications from addiction research towards the understanding and treatment of obesity. Addict Biol. 2011; 16(2): 189198.Google Scholar
22. Epstein, LH, Leddy, JJ, Temple, JL, Faith, MS. Food reinforcement and eating: a multilevel analysis. Psychol Bull. 2007; 133(5): 884906.Google Scholar
23. Stott, SRW, Ang, S-L. The generation of midbrain dopaminergic neurons. In Rubenstein J, Rakic P, eds. Patterning and Cell Type Specification in the Developing CNS and PNS. Amsterdam: Elsevier; 2013: 435453.Google Scholar
24. Berridge, KC. ‘Liking’ and ‘wanting’ food rewards: brain substrates and roles in eating disorders. Physiol Behav. 2009; 97(5): 537550.Google Scholar
25. Castellanos, EH, Charboneau, E, Dietrich, MS, et al. Obese adults have visual attention bias for food cue images: evidence for altered reward system function. Int J Obes (Lond). 2009; 33(9): 10631073.Google Scholar
26. Johnson, PM, Kenny, PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010; 13(5): 635641.CrossRefGoogle ScholarPubMed
27. Wang, GJ, Volkow, ND, Logan, J, et al. Brain dopamine and obesity. Lancet. 2001; 357(9253): 354357.Google Scholar
28. Stice, E, Spoor, S, Bohon, C, Small, DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008; 322(5900): 449452.Google Scholar
29. Douketis, JD, Macie, C, Thabane, L, Williamson, DF. Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Int J Obes (Lond). 2005; 29(10): 11531167.Google Scholar
30. Rubio, MA, Gargallo, M, Isabel Millán, A, Moreno, B. Drugs in the treatment of obesity: sibutramine, orlistat and rimonabant. Public Health Nutr. 2007; 10(10A): 12001205.Google Scholar
31. Madsbad, S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)—preclinical and clinical results. Best Pract Res Clin Endocrinol Metab. 2009; 23(4): 463477.Google Scholar
32. Hansen, KB, Knop, FK, Holst, JJ, Vilsbøll, T. Treatment of type 2 diabetes with glucagon-like peptide-1 receptor agonists. Int J Clin Pract. 2009; 63(8): 11541160.Google Scholar
33. Halford, JCG, Harrold, JA. 5-HT2C receptor agonists and the control of appetite. In Joost HG, ed. Appetite Control. Berlin Heidelberg: Springer; 2012: 349356.CrossRefGoogle ScholarPubMed
34. Bai, B, Wang, Y. The use of lorcaserin in the management of obesity: a critical appraisal. Drug Des Devel Ther. 2011; 5: 17.Google Scholar
35. Xu, J, Jian, B, Chu, R, et al. Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells. Am J Pathol. 2002; 161(6): 22092218.Google Scholar
36. Garvey, WT, Ryan, DH, Look, M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012; 95(2): 297308.Google Scholar
37. Billes, SK, Sinnayah, P, Cowley, MA. Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss. Pharmacol Res. 2014; 84: 111.Google Scholar
38. Greenway, FL, Whitehouse, MJ, Guttadauria, M, et al. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring). 2009; 17(1): 3039.Google Scholar
39. Hillemacher, T, Heberlein, A, Muschler, MA, Bleich, S, Frieling, H. Opioid modulators for alcohol dependence. Expert Opin Investig Drugs. 2011; 20(8): 10731086.Google Scholar
40. Wang, GJ, Tomasi, D, Volkow, ND, et al. Effect of combined naltrexone and bupropion therapy on the brain’s reactivity to food cues. Int J Obes (Lond). 2014; 38(5): 682688.Google Scholar