Postingestive reward acts through behavioral reinforcement and is conserved in obesity and after bariatric surgery

PLoS Biol. 2024 Dec 17;22(12):e3002936. doi: 10.1371/journal.pbio.3002936. eCollection 2024 Dec.

Abstract

Postingestive nutrient stimulation conditions food preferences through striatal dopamine and may be associated with blunted brain responses in obesity. In a cross-sectional study, we tested flavor-nutrient conditioning (FNC) with maltodextrin-enriched yogurt, with maltodextrin previously optimized for concentration and dextrose equivalents (n = 57), and to mask texture cues (n = 102). After conditioning, healthy volunteers (n = 52) increased preference for maltodextrin-paired (+102 kcal, CS+), relative to control (+1.8 kcal, CS-) flavors, as assessed according to intake, but not pleasantness. In a clinical study (n = 61), behavioral conditioning without effects on pleasantness was confirmed across pre-bariatric candidates with obesity, weight-stable post-surgery patients, and healthy controls, without significant differences between groups. Striatal dopamine D2-like receptor (DD2lR) availability, assessed with [123I]IBZM SPECT, was reduced in the obesity group and strongly correlated with conditioning strength and a measure of restrained eating in patients with gastric bypass. These results show that postingestive nutrient stimulation influences human food choices through behavioral reinforcement, and is conserved in obesity and after bariatric surgery. Trial Registration: ISRCTN17965026: Dopaminergic neurotransmission in dietary learning and obesity.

MeSH terms

  • Adult
  • Bariatric Surgery* / methods
  • Corpus Striatum / metabolism
  • Cross-Sectional Studies
  • Dopamine / metabolism
  • Feeding Behavior / physiology
  • Female
  • Food Preferences* / physiology
  • Humans
  • Male
  • Middle Aged
  • Obesity* / metabolism
  • Obesity* / physiopathology
  • Obesity* / surgery
  • Polysaccharides / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Reinforcement, Psychology
  • Reward*
  • Young Adult

Substances

  • Receptors, Dopamine D2
  • Polysaccharides
  • maltodextrin
  • Dopamine

Grants and funding

GR was funded by doctoral fellowships from Universidade de Lisboa (BD/2015Call) and Fundação para a Ciência e Tecnologia (FCT; https://www.fct.pt/; SFRH/BD/128783/2017). GR and AJOM were supported by the Champalimaud Foundation through a Clinical Kickstarter grant (https://www.fchampalimaud.org/). ABF was supported by a postdoctoral fellowship (SFRH/BPD/880972/2012) and is supported by a postdoctoral contract (DL 57/2016/CP1483/CT0001) and grant (PTDC/SAU-NUT/3507/2021) from FCT (https://www.fct.pt/). AJOM was supported by grants from the BIAL Foundation (176/10) (https://fundacaobial.com/) and from FCT, through a Junior Research and Career Development Award from the Harvard Medical Portugal Program (https://www.fct.pt/; HMSP/ICJ/0020/2011) and is funded by a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (https://erc.europa.eu/homepage; grant agreement No. 950357). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.