CC BY-NC-ND 4.0 · Exp Clin Endocrinol Diabetes 2022; 130(05): 290-295
DOI: 10.1055/a-1749-4852
Mini-Review

Obesity – A Matter of Motivation?

Ruth Hanssen
1   Max Planck Institute for Metabolism Research, Cologne, Germany
2   Policlinic for Endocrinology, Diabetology and Preventive Medicine (PEPD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
,
Sharmili E Thanarajah
1   Max Planck Institute for Metabolism Research, Cologne, Germany
3   Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany
,
Marc Tittgemeyer
1   Max Planck Institute for Metabolism Research, Cologne, Germany
4   Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Cologne, Germany
,
Jens C. Brüning
1   Max Planck Institute for Metabolism Research, Cologne, Germany
2   Policlinic for Endocrinology, Diabetology and Preventive Medicine (PEPD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
4   Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Cologne, Germany
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Abstract

Excessive food intake and reduced physical activity have long been established as primary causes of obesity. However, the underlying mechanisms causing this unhealthy behavior characterized by heightened motivation for food but not for physical effort are unclear. Despite the common unjustified stigmatization that obesity is a result of laziness and lack of discipline, it is becoming increasingly clear that high-fat diet feeding and obesity cause alterations in brain circuits that are critical for the control of motivational behavior.

In this mini-review, we provide a comprehensive overview of incentive motivation, its neural encoding in the dopaminergic mesolimbic system as well as its metabolic modulation with a focus on derangements of incentive motivation in obesity. We further discuss the emerging field of metabolic interventions to counteract motivational deficits and their potential clinical implications.

Key words

Obesity - motivation - GLP-1 - Dopaminergic midbrain


Publication History

Received: 29 July 2021
Received: 01 October 2021

Accepted: 26 October 2021

Article published online:
18 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Bhaskaran K, Douglas I, Forbes H. et al. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5 24 million UK adults. Lancet 2014; 384: 755-765
    CrossrefPubMedGoogle Scholar
  • 2 Flegal KM, Kit BK, Orpana H. et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis. JAMA 2013; 309: 71-82
    CrossrefPubMedGoogle Scholar
  • 3 Bhaskaran K, Dos-Santos-Silva I, Leon DA. et al. Association of BMI with overall and cause-specific mortality: A population-based cohort study of 3 6 million adults in the UK. Lancet Diabetes Endocrinol 2018; 6: 944-953
    CrossrefPubMedGoogle Scholar
  • 4 Killeen PR. Incentive theory. Nebraska Symp Motiv 1981; 29: 169-216
    PubMedGoogle Scholar
  • 5 De Houwer J, Hughes S. The psychology of learning: An introduction from a functional-cognitive perspective. MPI Press. 2020
    PubMedGoogle Scholar
  • 6 Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav 2004; 81: 179-209
    CrossrefPubMedGoogle Scholar
  • 7 De Araujo IE, Schatzker M, Small DM. Rethinking food reward. Annu Rev Psychol 2019; 71: 139-164
    CrossrefPubMedGoogle Scholar
  • 8 Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 2003; 299: 1898-1902
    CrossrefPubMedGoogle Scholar
  • 9 Tobler PN, Fiorillo CD, Schultz W. Adaptive coding of reward value by dopamine neurons. Science 2005; 307: 1642-1645
    CrossrefPubMedGoogle Scholar
  • 10 Mohebi A, Pettibone JR, Hamid AA. et al. Dissociable dopamine dynamics for learning and motivation. Nature 2019; 570: 65-70
    CrossrefPubMedGoogle Scholar
  • 11 van Swieten MMH, Bogacz R. Modeling the effects of motivation on choice and learning in the basal ganglia. Plos Comput Biol 2020; 16: e1007465
    CrossrefPubMedGoogle Scholar
  • 12 Bartra O, McGuire JT, Kable JW. The valuation system: A coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value. Neuroimage 2013; 76: 412-427
    CrossrefPubMedGoogle Scholar
  • 13 Howe MW, Tierney PL, Sandberg SG. et al. Prolonged dopamine signalling in striatum signals proximity and value of distant rewards. Nature 2013; 500: 575-579
    CrossrefPubMedGoogle Scholar
  • 14 Knutson B, Greer SM. Anticipatory affect: Neural correlates and consequences for choice. Philos Trans R Soc Lond B Biol Sci 2008; 363: 3771-3786
    CrossrefPubMedGoogle Scholar
  • 15 Berke JD. What does dopamine mean?. Nat Neurosci 2018; 21: 787-793
    CrossrefPubMedGoogle Scholar
  • 16 Salamone JD, Correa M, Yang JH. et al. Dopamine, effort-based choice, and behavioral economics: Basic and translational research. Front Behav Neurosci 2018; 12: 52
    CrossrefPubMedGoogle Scholar
  • 17 Chong TT, Bonnelle V, Manohar S. et al. Dopamine enhances willingness to exert effort for reward in Parkinson’s disease. Cortex 2015; 69: 40-46
    CrossrefPubMedGoogle Scholar
  • 18 Le Bouc R, Rigoux L, Schmidt L. et al. Computational dissection of dopamine motor and motivational functions in humans. J Neurosci 2016; 36: 6623-6633
    CrossrefPubMedGoogle Scholar
  • 19 Kenny PJ. Reward mechanisms in obesity: New insights and future directions. Neuron 2011; 69: 664-679
    CrossrefPubMedGoogle Scholar
  • 20 Mazzone CM, Liang-Guallpa J, Li C. et al. High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nat Neurosci 2020; 23: 1253-1266
    CrossrefPubMedGoogle Scholar
  • 21 Adams WK, Sussman JL, Kaur S. et al. Long-term, calorie-restricted intake of a high-fat diet in rats reduces impulse control and ventral striatal D2 receptor signalling – two markers of addiction vulnerability. Eur J Neurosci 2015; 42: 3095-3104
    CrossrefPubMedGoogle Scholar
  • 22 van de Giessen E, la Fleur SE, Eggels L. et al. High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity. Int J Obes 2013; 37: 754-757
    CrossrefPubMedGoogle Scholar
  • 23 Wang GJ, Volkow ND, Logan J. et al. Brain dopamine and obesity. Lancet 2001; 357: 354-357
    CrossrefPubMedGoogle Scholar
  • 24 Haltia LT, Rinne JO, Merisaari H. et al. Effects of intravenous glucose on dopaminergic function in the human brain in vivo. Synapse 2007; 61: 748-756
    CrossrefPubMedGoogle Scholar
  • 25 Stice E, Spoor S, Bohon C. et al. Relation of reward from food intake and anticipated food intake to obesity: A functional magnetic resonance imaging study. J Abnorm Psychol 2008; 117: 924-935
    CrossrefPubMedGoogle Scholar
  • 26 Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: Implications for obesity. Trends Cogn Sci 2011; 15: 37-46
    CrossrefPubMedGoogle Scholar
  • 27 van Bloemendaal L, Veltman DJ, Ten Kulve JS. et al. Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans. Diabetes Obes Metab 2015; 17: 878-886
    CrossrefPubMedGoogle Scholar
  • 28 van der Zwaal EM, de Weijer BA, van de Giessen EM. et al. Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss. Eur Neuropsychopharmacol 2016; 26: 1190-1200
    CrossrefPubMedGoogle Scholar
  • 29 de Weijer BA, van de Giessen E, Janssen I. et al. Striatal dopamine receptor binding in morbidly obese women before and after gastric bypass surgery and its relationship with insulin sensitivity. Diabetologia 2014; 57: 1078-1080
    CrossrefPubMedGoogle Scholar
  • 30 Steele KE, Prokopowicz GP, Schweitzer MA. et al. Alterations of central dopamine receptors before and after gastric bypass surgery. Obes Surg 2010; 20: 369-374
    CrossrefPubMedGoogle Scholar
  • 31 Reddy IA, Smith NK, Erreger K. et al. Bile diversion, a bariatric surgery, and bile acid signaling reduce central cocaine reward. PLoS Biol 2018; 16: e2006682
    CrossrefPubMedGoogle Scholar
  • 32 Mathar D, Horstmann A, Pleger B. et al. Is it worth the effort? Novel insights into obesity-associated alterations in cost-benefit decision-making. Front Behav Neurosci 2015; 9: 360
    PubMedGoogle Scholar
  • 33 Epstein LH, Temple JL, Neaderhiser BJ. et al. Food reinforcement, the dopamine D2 receptor genotype, and energy intake in obese and nonobese humans. Behav Neurosci 2007; 121: 877-886
    CrossrefPubMedGoogle Scholar
  • 34 Giesen JC, Havermans RC, Douven A. et al. Will work for snack food: The association of BMI and snack reinforcement. Obesity (Silver Spring, Md) 2010; 18: 966-970
    CrossrefPubMedGoogle Scholar
  • 35 McCutcheon JE. The role of dopamine in the pursuit of nutritional value. Physiol Behav 2015; 152: 408-415
    CrossrefPubMedGoogle Scholar
  • 36 Fernandes AB, Alves da Silva J, Almeida J. et al. Postingestive modulation of food seeking depends on vagus-mdiated dopamine neuron activity. Neuron 2020; 106: 778-788 e6
    CrossrefPubMedGoogle Scholar
  • 37 Edwin TS, Backes H, DiFeliceantonio AG. et al. Food intake recruits orosensory and post-ingestive dopaminergic circuits to affect eating desire in humans. Cell Metab 2019; 29: 695-706 e4
    CrossrefPubMedGoogle Scholar
  • 38 Naef L, Pitman KA, Borgland SL. Mesolimbic dopamine and its neuromodulators in obesity and binge eating. CNS Spectrum 2015; 20: 574-583
    CrossrefPubMedGoogle Scholar
  • 39 Fulton S, Pissios P, Manchon RP. et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 2006; 51: 811-822
    CrossrefPubMedGoogle Scholar
  • 40 Liu S, Borgland SL. Regulation of the mesolimbic dopamine circuit by feeding peptides. Neuroscience 2015; 289: 19-42
    CrossrefPubMedGoogle Scholar
  • 41 Figlewicz DP. Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat: Historical perspective. Brain Res 2016; 1645: 68-70
    CrossrefPubMedGoogle Scholar
  • 42 Abizaid A, Gao Q, Horvath TL. Thoughts for food: Brain mechanisms and peripheral energy balance. Neuron 2006; 51: 691-702
    CrossrefPubMedGoogle Scholar
  • 43 Al Massadi O, Nogueiras R, Dieguez C. et al. Ghrelin and food reward. Neuropharmacology 2019; 148: 131-138
    CrossrefPubMedGoogle Scholar
  • 44 Jerlhag E. Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine. Addict Biol 2008; 13: 358-363
    CrossrefPubMedGoogle Scholar
  • 45 Jerlhag E, Egecioglu E, Dickson SL. et al. Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol 2007; 12: 6-16
    CrossrefPubMedGoogle Scholar
  • 46 Skibicka KP, Hansson C, Alvarez-Crespo M. et al. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience 2011; 180: 129-137
    CrossrefPubMedGoogle Scholar
  • 47 Jerlhag E, Janson AC, Waters S. et al. Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by ghrelin in rats. PLoS One 2012; 7: e49557
    CrossrefPubMedGoogle Scholar
  • 48 Lockie SH, Dinan T, Lawrence AJ. et al. Diet-induced obesity causes ghrelin resistance in reward processing tasks. Psychoneuroendocrinology 2015; 62: 114-120
    CrossrefPubMedGoogle Scholar
  • 49 Kleinridders A, Pothos EN. Impact of brain insulin signaling on dopamine function, food intake, reward, and emotional behavior. Curr Nutr Rep 2019; 8: 83-91
    CrossrefPubMedGoogle Scholar
  • 50 Labouèbe G, Liu S, Dias C. et al. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat Neurosci 2013; 16: 300-308
    CrossrefPubMedGoogle Scholar
  • 51 Figlewicz DP, Szot P, Chavez M. et al. Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra. Brain Res 1994; 644: 331-334
    CrossrefPubMedGoogle Scholar
  • 52 Mebel DM, Wong JC, Dong YJ. et al. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur J Neurosci 2012; 36: 2336-2346
    CrossrefPubMedGoogle Scholar
  • 53 Naef L, Seabrook L, Hsiao J. et al. Insulin in the ventral tegmental area reduces cocaine-evoked dopamine in the nucleus accumbens in vivo. Eur J Neurosci 2019; 50: 2146-2155
    CrossrefPubMedGoogle Scholar
  • 54 Wang XF, Liu JJ, Xia J. et al. Endogenous glucagon-like peptide-1 suppresses high-fat food intake by reducing synaptic drive onto mesolimbic dopamine neurons. Cell Rep 2015; 12: 726-733
    CrossrefPubMedGoogle Scholar
  • 55 Dickson SL, Shirazi RH, Hansson C. et al. The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: A new role for mesolimbic GLP-1 receptors. J Neurosci 2012; 32: 4812-4820
    CrossrefPubMedGoogle Scholar
  • 56 Konanur VR, Hsu TM, Kanoski SE. et al. Phasic dopamine responses to a food-predictive cue are suppressed by the glucagon-like peptide-1 receptor agonist exendin-4. Physiol Behav 2020; 215: 112771
    CrossrefPubMedGoogle Scholar
  • 57 Mietlicki-Baase EG, McGrath LE, Koch-Laskowski K. et al. Amylin receptor activation in the ventral tegmental area reduces motivated ingestive behavior. Neuropharmacology 2017; 123: 67-79
    CrossrefPubMedGoogle Scholar
  • 58 Mietlicki-Baase EG, Reiner DJ, Cone JJ. et al. Amylin modulates the mesolimbic dopamine system to control energy balance. Neuropsychopharmacology 2015; 40: 372-385
    CrossrefPubMedGoogle Scholar
  • 59 Kalafateli AL, Vallöf D, Jerlhag E. Activation of amylin receptors attenuates alcohol-mediated behaviours in rodents. Addict Biol 2019; 24: 388-402
    CrossrefPubMedGoogle Scholar
  • 60 Liu J, Perez SM, Zhang W. et al. Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala. Mol Psychiatry 2011; 16: 1024-1038
    CrossrefPubMedGoogle Scholar
  • 61 Leshan RL, Opland DM, Louis GW. et al. Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala. J Neurosci 2010; 30: 5713-5723
    CrossrefPubMedGoogle Scholar
  • 62 Leinninger GM, Opland DM, Jo YH. et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab 2011; 14: 313-323
    CrossrefPubMedGoogle Scholar
  • 63 Plassmann H, Schelski DS, Simon MC. et al. How we decide what to eat: Toward an interdisciplinary model of gut-brain interactions. Wiley Interdiscip Rev Cogn Sci 2021; e1562
    PubMedGoogle Scholar
  • 64 Hanssen R, Kretschmer AC, Rigoux L. et al. GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans. Mol Metab 2021; 45: 101163
    CrossrefPubMedGoogle Scholar
  • 65 Edwin Thanarajah S, Iglesias S, Kuzmanovic B. et al. Modulation of midbrain neurocircuitry by intranasal insulin. Neuroimage 2019; 194: 120-127
    CrossrefPubMedGoogle Scholar
  • 66 Hamer JA, Testani D, Mansur RB. et al. Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression. Exp Neurol 2019; 315: 1-8
    CrossrefPubMedGoogle Scholar
  • 67 Pozzi M, Mazhar F, Peeters G. et al. A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists: Further link between metabolism and psychopathology: Special Section on “Translational and Neuroscience Studies in Affective Disorders”. Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders. J Affect Disord 2019; 257: 774-778
    CrossrefPubMedGoogle Scholar
  • 68 Pi-Sunyer X, Astrup A, Fujioka K. et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015; 373: 11-22
    CrossrefPubMedGoogle Scholar
  • 69 Schmidt HD, Mietlicki-Baase EG, Ige KY. et al. Glucagon-like peptide-1 receptor activation in the ventral tegmental area decreases the reinforcing efficacy of cocaine. Neuropsychopharmacology 2016; 41: 1917-1928
    CrossrefPubMedGoogle Scholar
  • 70 Eren-Yazicioglu CY, Yigit A, Dogruoz RE. et al. Can GLP-1 be a target for reward system related disorders? A qualitative synthesis and systematic review analysis of studies on palatable food, drugs of abuse, and alcohol. Front Behav Neurosci 2020; 14: 614884
    CrossrefPubMedGoogle Scholar