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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2024; 18(03): 100-106
DOI: 10.1055/a-2339-9667
Review

Der Stoffwechsel und die Motivation: Ein Teufelskreis?

Metabolism and Motivation: A Vicious Circle?
Alina Chloé Kretschmer‡
1   Medizinische Fakultät und Universitätsklinikum Köln, Poliklinik für Endokrinologie, Diabetologie und Präventivmedizin (PEPD), Universität zu Köln, Köln, Deutschland
,
Sita Arjune‡
1   Medizinische Fakultät und Universitätsklinikum Köln, Poliklinik für Endokrinologie, Diabetologie und Präventivmedizin (PEPD), Universität zu Köln, Köln, Deutschland
,
Sharmili Edwin Thanarajah
2   Max-Planck-Institut für Stoffwechselforschung, Köln, Köln, Deutschland
3   Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Universitätsklinikum, Goethe-Universität Frankfurt, Frankfurt, Deutschland
,
Ruth Hanssen
1   Medizinische Fakultät und Universitätsklinikum Köln, Poliklinik für Endokrinologie, Diabetologie und Präventivmedizin (PEPD), Universität zu Köln, Köln, Deutschland
2   Max-Planck-Institut für Stoffwechselforschung, Köln, Köln, Deutschland
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Zusammenfassung

Die zunehmende Adipositas-Pandemie stellt eines der größten Gesundheitsprobleme des 21. Jahrhunderts dar, mit zahlreichen Komorbiditäten und dramatisch erhöhter Morbidität und Mortalität. Während übermäßige Nahrungsaufnahme und verminderte körperliche Aktivität als Hauptursachen bekannt sind, bleiben die zugrundeliegenden Mechanismen dieses maladaptiven langfristig gesundheitsschädlichen Verhaltens unzureichend verstanden. Dieser Artikel beleuchtet die Rolle des mesolimbischen dopaminergen Systems in Entscheidungsprozessen für belohnungsbezogenes Verhalten, insbesondere in Bezug auf Ernährung, sowie die pathophysiologische Dysregulation dieser Verhaltensprozesse bei Adipositas. Da das Zusammenspiel von Stoffwechselsignalen und Umweltreizen im Gehirn wesentlich unser adaptives Verhalten steuert, könnte ein besseres Verständnis dieser Prozesse zu wirksameren präventiven und therapeutischen Strategien für Adipositas und ihre Folgen führen.

Abstract

The growing obesity pandemic is one of the biggest health problems of the 21st century, with numerous comorbidities and dramatically increased morbidity and mortality. While excessive food intake and reduced physical activity are known to be the main causes, the underlying mechanisms of this maladaptive long-term harmful behaviour remain poorly understood. This narrative review examines the role of the mesolimbic dopaminergic system in decision-making processes for reward-related behaviour, especially with regard to nutrition, as well as the pathophysiological dysregulation of these behavioural processes in obesity. As the integration of metabolic signals and environmental stimuli on a neural level significantly controls our adaptive behaviour, a better understanding of these processes could lead to more effective preventive and therapeutic strategies for obesity and its consequences.

Schlüsselwörter

Adipositas - Motivation - Assoziationslernen - Dopamin - Insulinresistenz

Keywords

obesity - motivation - association learning - dopamine - insulin resistance


Publication History

Article published online:
20 September 2024

© 2024. Thieme. All rights reserved.

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  • Literatur

  • 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
    CrossrefPubMedSearch in Google 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
    CrossrefPubMedSearch in Google Scholar
  • 3 Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav 2004; 81: 179-209
    CrossrefPubMedSearch in Google Scholar
  • 4 de Araujo IE, Schatzker M, Small DM. Rethinking Food Reward. Annu Rev Psychol 2020; 71: 139-164
    CrossrefPubMedSearch in Google Scholar
  • 5 Coddington LT, Lindo SE, Dudman JT. Mesolimbic dopamine adapts the rate of learning from action. Nature 2023; 614: 294-302
    CrossrefPubMedSearch in Google Scholar
  • 6 Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science 2003; 299: 1898-1902
    CrossrefPubMedSearch in Google Scholar
  • 7 Tobler PN, Fiorillo CD, Schultz W. Adaptive coding of reward value by dopamine neurons. Science 2005; 307: 1642-1645
    CrossrefPubMedSearch in Google Scholar
  • 8 Jeong H, Taylor A, Floeder JR. et al. Mesolimbic dopamine release conveys causal associations. Science 2022; 378: eabq6740
    CrossrefPubMedSearch in Google Scholar
  • 9 Schultz W. Reward signaling by dopamine neurons. Neuroscientist 2001; 7: 293-302
    CrossrefPubMedSearch in Google Scholar
  • 10 Schultz W, Dayan P, Montague PR. A neural substrate of prediction and reward. Science 1997; 275: 1593-1599
    CrossrefPubMedSearch in Google Scholar
  • 11 Mohebi A, Pettibone JR, Hamid AA. et al. Dissociable dopamine dynamics for learning and motivation. Nature 2019; 570: 65-70
    CrossrefPubMedSearch in Google Scholar
  • 12 Syed ECJ, Grima LL, Magill PJ. et al. Action initiation shapes mesolimbic dopamine encoding of future rewards. Nat Neurosci 2016; 19: 34-36
    CrossrefPubMedSearch in Google Scholar
  • 13 Tanaka S, O'Doherty JP, Sakagami M. The cost of obtaining rewards enhances the reward prediction error signal of midbrain dopamine neurons. Nat Commun 2019; 10: 3674
    CrossrefPubMedSearch in Google Scholar
  • 14 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
    CrossrefPubMedSearch in Google Scholar
  • 15 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
    CrossrefPubMedSearch in Google Scholar
  • 16 Knutson B, Greer SM. Anticipatory affect: neural correlates and consequences for choice. Philos Trans R Soc Lond B Biol Sci 2008; 363: 3771-3786
    CrossrefPubMedSearch in Google 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
    CrossrefPubMedSearch in Google Scholar
  • 18 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
    CrossrefPubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 Nieh EH, Matthew GA, Allsop SA. et al. Decoding neural circuits that control compulsive sucrose seeking. Cell 2015; 160: 528-541
    CrossrefPubMedSearch in Google Scholar
  • 21 Reichenbach A, Clarke EE, Stark R. et al. Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum. Elife 2022; 11: e72668
    CrossrefPubMedSearch in Google Scholar
  • 22 Rossi MA, Basiri ML, Liu Y. et al. Transcriptional and functional divergence in lateral hypothalamic glutamate neurons projecting to the lateral habenula and ventral tegmental area. Neuron 2021; 109: 3823-3837 e6
    CrossrefPubMedSearch in Google Scholar
  • 23 Zhang Q, Tang Q, Purohit NM. et al. Food-induced dopamine signaling in AgRP neurons promotes feeding. Cell Rep 2022; 41: 111718
    CrossrefPubMedSearch in Google Scholar
  • 24 Han W, Tellez LA, Perkins MH. et al. A Neural Circuit for Gut-Induced Reward. Cell 2018; 175: 665-678 e23
    CrossrefPubMedSearch in Google Scholar
  • 25 Abizaid A, Gao Q, Horvath TL. Thoughts for food: brain mechanisms and peripheral energy balance. Neuron 2006; 51: 691-702
    CrossrefPubMedSearch in Google Scholar
  • 26 Al Massadi O, Noguieiras R, Dieguez C. et al. Ghrelin and food reward. Neuropharmacology 2019; 148: 131-138
    CrossrefPubMedSearch in Google Scholar
  • 27 Jerlhag E. Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine. Addict Biol 2008; 13: 358-363
    CrossrefPubMedSearch in Google Scholar
  • 28 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
    CrossrefPubMedSearch in Google Scholar
  • 29 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
    CrossrefPubMedSearch in Google Scholar
  • 30 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
    CrossrefPubMedSearch in Google Scholar
  • 31 Lockie SH, Dinan T, Lawrence AJ. et al. Diet-induced obesity causes ghrelin resistance in reward processing tasks. Psychoneuroendocrinology 2015; 62: 114-120
    CrossrefPubMedSearch in Google Scholar
  • 32 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
    CrossrefPubMedSearch in Google Scholar
  • 33 Labouebe 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
    CrossrefPubMedSearch in Google Scholar
  • 34 Mebel DM, Wong JCY, 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
    CrossrefPubMedSearch in Google Scholar
  • 35 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
    CrossrefPubMedSearch in Google Scholar
  • 36 Figlewicz D, Szot P, Chavez M. et al. Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra. Brain Res 1994; 644: 331-334
    CrossrefPubMedSearch in Google Scholar
  • 37 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
    CrossrefPubMedSearch in Google Scholar
  • 38 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
    CrossrefPubMedSearch in Google Scholar
  • 39 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
    CrossrefPubMedSearch in Google Scholar
  • 40 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
    CrossrefPubMedSearch in Google Scholar
  • 41 Mietlicki-Baase EG, Reiner DJ, Cone JJ. et al. Amylin modulates the mesolimbic dopamine system to control energy balance. Neuropsychopharmacology 2015; 40: 372-385
    CrossrefPubMedSearch in Google Scholar
  • 42 Kalafateli AL, Vallof D, Jerlhag E. Activation of amylin receptors attenuates alcohol-mediated behaviours in rodents. Addict Biol 2019; 24: 388-402
    CrossrefPubMedSearch in Google Scholar
  • 43 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
    CrossrefPubMedSearch in Google Scholar
  • 44 Thanarajah SE, Backes H, DiFeiceantonio 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
    CrossrefPubMedSearch in Google Scholar
  • 45 DiFeliceantonio AG, Coppin G, Rigoux L. et al. Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward. Cell Metab 2018; 28: 33-44 e3
    CrossrefPubMedSearch in Google Scholar
  • 46 McDougle M, de Araujo A, Singh A. et al. Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 2024; 36: 393-407 e7
    CrossrefPubMedSearch in Google Scholar
  • 47 Dohnalova L, Lundgren P, Carty JRE. et al. A microbiome-dependent gut-brain pathway regulates motivation for exercise. Nature 2022; 612: 739-747
    CrossrefPubMedSearch in Google Scholar
  • 48 Rihm JS, Menz MM, Schultz H. et al. Sleep Deprivation Selectively Upregulates an Amygdala-Hypothalamic Circuit Involved in Food Reward. J Neurosci 2019; 39: 888-899
    CrossrefPubMedSearch in Google Scholar
  • 49 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
    CrossrefPubMedSearch in Google Scholar
  • 50 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 (Lond) 2013; 37: 754-757
    CrossrefPubMedSearch in Google Scholar
  • 51 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
    CrossrefPubMedSearch in Google Scholar
  • 52 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
    CrossrefPubMedSearch in Google Scholar
  • 53 Wang GJ, Volkow ND, Logan J. et al. Brain dopamine and obesity. Lancet 2001; 357: 354-357
    CrossrefPubMedSearch in Google Scholar
  • 54 Giros B, el Mestikawy S, Godinot N. et al. Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol 1992; 42: 383-390
    PubMedSearch in Google Scholar
  • 55 Wu C, Garamszegi SP, Xie X. et al. Altered Dopamine Synaptic Markers in Postmortem Brain of Obese Subjects. Front Hum Neurosci 2017; 11: 386
    CrossrefPubMedSearch in Google Scholar
  • 56 Stice E, Spoor S, Nohon 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
    CrossrefPubMedSearch in Google Scholar
  • 57 Volkow ND, Wang GJ, Baler RD. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci 2011; 15: 37-46
    CrossrefPubMedSearch in Google Scholar
  • 58 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
    CrossrefPubMedSearch in Google Scholar
  • 59 Perszyk EE, Hutelin Z, Trinh J. et al. Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity. Nutrients 2021; 13: 1203
    CrossrefPubMedSearch in Google Scholar
  • 60 Thanarajah SE, DiFeliceantonio AG, Albus K. et al. Habitual daily intake of a sweet and fatty snack modulates reward processing in humans. Cell Metab 2023; 35: 571-584 e6
    CrossrefPubMedSearch in Google Scholar
  • 61 Wang W. et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med 2024; 30: 168-176
    CrossrefPubMedSearch in Google Scholar
  • 62 Jerlhag E. The therapeutic potential of glucagon-like peptide-1 for persons with addictions based on findings from preclinical and clinical studies. Front Pharmacol 2023; 14: 1063033
    CrossrefPubMedSearch in Google Scholar
  • 63 Klausen MK, Jensen ME, Møller M. et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight 2022; 7: e159863
    CrossrefPubMedSearch in Google Scholar
  • 64 van Galen KA, Schrantee A, Ter Horst KW. et al. Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study. Nat Metab 2023; 5: 1059-1072
    CrossrefPubMedSearch in Google Scholar