The expression of genes in top obesity-associated ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward.
Auteur(s) :
Ndiaye, Fatou K. [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Huyvaert, Marlene [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Ortalli, Ana [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Canouil, Mickaël [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Lecoeur, Cecile [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Verbanck, Marie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Lobbens, Stéphane [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Khamis, Amna [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Marselli, Lorella [Auteur]
Marchetti, Piero [Auteur]
Pattou Kerr-Conte, Julie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Pattou, Francois [Auteur]
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Marre, Michel [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Université Sorbonne Paris Cité [USPC]
Roussel, Ronan [Auteur]
Université Sorbonne Paris Cité [USPC]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Balkau, Beverley [Auteur]
Université Paris-Saclay
Froguel, Philippe [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Bonnefond, Amelie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Huyvaert, Marlene [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Ortalli, Ana [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Canouil, Mickaël [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Lecoeur, Cecile [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Verbanck, Marie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Lobbens, Stéphane [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Khamis, Amna [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Marselli, Lorella [Auteur]
Marchetti, Piero [Auteur]
Pattou Kerr-Conte, Julie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Pattou, Francois [Auteur]
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Marre, Michel [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Université Sorbonne Paris Cité [USPC]
Roussel, Ronan [Auteur]
Université Sorbonne Paris Cité [USPC]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Balkau, Beverley [Auteur]
Université Paris-Saclay
Froguel, Philippe [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Bonnefond, Amelie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Titre de la revue :
International Journal of Obesity
Nom court de la revue :
Int J Obes (Lond)
Numéro :
44
Pagination :
539–543
Date de publication :
2019-08-06
ISSN :
1476-5497
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Background
Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for ...
Lire la suite >Background Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for understanding how these genetic loci physiologically impact disease development. Methods We performed a PCR-free expression assay targeting genes located nearby the GWAS-identified SNPs associated with BMI/obesity in a large panel of human tissues. Furthermore, we analyzed several genetic risk scores (GRS) summing GWAS-identified alleles associated with increased BMI in 4236 individuals. Results We found that the expression of BMI/obesity susceptibility genes was strongly enriched in the brain, especially in the insula (p = 4.7 × 10–9) and substantia nigra (p = 6.8 × 10–7), which are two brain regions involved in addiction and reward. Inversely, we found that top obesity/BMI-associated loci, including FTO, showed the strongest gene expression enrichment in the two brain regions. Conclusions Our data suggest for the first time that the susceptibility genes for common obesity may have an effect on eating addiction and reward behaviors through their high expression in substantia nigra and insula, i.e., a different pattern from monogenic obesity genes that act in the hypothalamus and cause hyperphagia. Further epidemiological studies with relevant food behavior phenotypes are necessary to confirm these findings.Lire moins >
Lire la suite >Background Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for understanding how these genetic loci physiologically impact disease development. Methods We performed a PCR-free expression assay targeting genes located nearby the GWAS-identified SNPs associated with BMI/obesity in a large panel of human tissues. Furthermore, we analyzed several genetic risk scores (GRS) summing GWAS-identified alleles associated with increased BMI in 4236 individuals. Results We found that the expression of BMI/obesity susceptibility genes was strongly enriched in the brain, especially in the insula (p = 4.7 × 10–9) and substantia nigra (p = 6.8 × 10–7), which are two brain regions involved in addiction and reward. Inversely, we found that top obesity/BMI-associated loci, including FTO, showed the strongest gene expression enrichment in the two brain regions. Conclusions Our data suggest for the first time that the susceptibility genes for common obesity may have an effect on eating addiction and reward behaviors through their high expression in substantia nigra and insula, i.e., a different pattern from monogenic obesity genes that act in the hypothalamus and cause hyperphagia. Further epidemiological studies with relevant food behavior phenotypes are necessary to confirm these findings.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Date de dépôt :
2024-01-19T23:46:22Z
2024-09-23T15:01:55Z
2024-09-23T15:05:51Z
2024-09-23T15:01:55Z
2024-09-23T15:05:51Z