The endocannabinoid system is modulated in reward and homeostatic brain regions following diet-induced obesity in rats: a cluster analysis approach

Autor: Mary C. Olmstead, Alexandra Hertz, Romain Bourdy, Yannick Goumon, Katia Befort, Dominique Filliol, Virginie Andry, Jorge E. Mendoza
Přispěvatelé: Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Goumon, Yannick, Queen's University [Kingston, Canada]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: European Journal of Nutrition
European Journal of Nutrition, Springer Verlag, 2021, ⟨10.1007/s00394-021-02613-0⟩
European Journal of Nutrition, 2021, 60 (8), pp.4621-4633. ⟨10.1007/s00394-021-02613-0⟩
ISSN: 1436-6215
1436-6207
Popis: Objectives Increased availability of high-calorie palatable food in most countries has resulted in overconsumption of these foods, suggesting that excessive eating is driven by pleasure, rather than metabolic need. The behavior contributes to the rise in eating disorders, obesity, and associated pathologies like diabetes, cardiac disease, and cancers. The mesocorticolimbic dopamine and homeostatic circuits are interconnected and play a central role in palatable food intake. The endocannabinoid system is expressed in these circuits and represents a potent regulator of feeding, but the impact of an obesogenic diet on its expression is not fully known. Methods Food intake and body weight were recorded in male Wistar rats over a 6-week free-choice regimen of high fat and sugar; transcriptional regulations of the endocannabinoid system were examined post-mortem in brain reward regions (prefrontal cortex, nucleus accumbens, ventral tegmental area, and arcuate nucleus). K-means cluster analysis was used to classify animals based on individual sensitivity to obesity and palatable food intake. Endocannabinoid levels were quantified in the prefrontal cortex and nucleus accumbens. Gene expression in dopamine and homeostatic systems, including ghrelin and leptin receptors, and classical homeostatic peptides, were also investigated. Results The free-choice high-fat -and sugar diet induced hyperphagia and obesity in rats. Cluster analysis revealed that the propensity to develop obesity and excessive palatable food intake was differently associated with dopamine and endocannabinoid system gene expression in reward and homeostatic brain regions. CB2 receptor mRNA was increased in the nucleus accumbens of high sugar consumers, whereas CB1 receptor mRNA was decreased in obesity prone rats. Conclusions Transcriptional data are consistent with observations of altered dopamine function in rodents that have access to an obesogenic diet and point to cannabinoid receptors as GPCR targets involved in neuroplasticity mechanisms associated with maladaptive intake of palatable food. Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02613-0.
Databáze: OpenAIRE
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