Preclinical and Clinical Evidence for a Distinct Regulation of Mu Opioid and Type 1 Cannabinoid Receptor Genes Expression in Obesity

Pucci, Mariangela and Micioni Di Bonaventura, Maria Vittoria and Vezzoli, Valeria and Zaplatic, Elizabeta and Massimini, Marcella and Mai, Stefania and Sartorio, Alessandro and Scacchi, Massimo and Persani, Luca and Maccarrone, Mauro and Cifani, Carlo and D’Addario, Claudio (2019) Preclinical and Clinical Evidence for a Distinct Regulation of Mu Opioid and Type 1 Cannabinoid Receptor Genes Expression in Obesity. Frontiers in Genetics, 10. ISSN 1664-8021

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Abstract

Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in humans with obesity and healthy controls. A significant and selective increase in type 1 cannabinoid receptor gene (Cnr1) expression was observed at the beginning of obesity development (5 weeks on high fat diet) as well as after 21 weeks of high diet exposure. After 5 weeks on high fat diet, selective up-regulation of mu opioid receptor gene (Oprm1) expression was also observed. Consistently, epigenetic studies showed a selective and significant decrease in DNA methylation at specific CpG sites at both gene promoters in overweight rats, but only after 5 weeks on high fat diet. Moreover, significantly lower levels of DNA methylation were observed at selected CpG sites of both receptor gene promoters, analyzed in peripheral blood mononuclear cells from younger (<30 years old) humans with obesity, as well as in those with shorter time length from disease onset. Taken together, we here provide evidence of selective, synergistic and time-dependent transcriptional regulation of CNR1 and OPRM1 genes in overweight rats, as well as in human subjects. These alterations in genes regulation could contribute to the development of the obese phenotype, and we thus suggest CNR1 and OPRM1 epigenetic modulation as possible biomarkers of obesity development. Due to the reversible nature of the epigenetic hallmark, our data might also open new avenue to early environmental strategies of intervention.

Item Type: Article
Subjects: Archive Paper Guardians > Medical Science
Depositing User: Unnamed user with email support@archive.paperguardians.com
Date Deposited: 06 Feb 2023 07:46
Last Modified: 02 Jan 2024 13:07
URI: http://archives.articleproms.com/id/eprint/136

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