Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets
INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocor...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/28170 |
| Acceso en línea: | https://hdl.handle.net/10171/28170 |
| Access Level: | acceso abierto |
| Palabra clave: | Genome wide association Childhood obesity Eating behavior Food intake Body fat Polymorphisms Insulin Mutations |
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Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat dietsSantos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638Cruz, R. (R.) de la|||/items/0bf030f8-bd1d-45f1-9a7b-6015e79e71b5Holst, C. (C.)|||/items/d9318459-9342-49cf-a2da-d6aeb6914a12Grau, K. (K.)|||/items/dee32024-fa7a-4ab1-8273-3a025e0e73fcNaranjo, C. (C.)|||/items/9b345f66-f586-434d-84a8-02cfa612745eMaiz, A. (Alberto)|||/items/ceb4045f-526f-4f1b-9aa1-9ac32e034478Astrup, A. (Arne)|||/items/f6a0e5d3-b236-40b9-a5a3-c380ae3446f2Saris, W.H.M. (Wim H. M.)|||/items/72a768f2-c225-4139-86ea-e7895ef2a736MacDonald, I. (Ian)|||/items/c1052005-3adc-4628-8276-f2803549627fOppert, J.M. (Jean M.)|||/items/93cbce83-69c1-4820-9e4b-a4003c9c5629Hansen, T. (Torben)|||/items/de8447d9-7fad-4ca8-9a14-fbe1493a5e91Pedersen, O. (Oluf)|||/items/7f57f180-6e9b-44fd-914e-e2f48b9c94e7Sørensen, T.I.A (Thorkild I. A.)|||/items/be862a34-8bb8-4755-ac24-3ed3689e43d0Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131Genome wide associationChildhood obesityEating behaviorFood intakeBody fatPolymorphismsInsulinMutationsINTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06), rs6014646-rs6024730 (p = 0.05) and rs3746619-rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans.Public Library of SciencesDadun. Depósito Académico Digital Universidad de Navarra20132013-03-2220112011-01-0120112011-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/28170reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/281702026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| title |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| spellingShingle |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets Santos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638 Genome wide association Childhood obesity Eating behavior Food intake Body fat Polymorphisms Insulin Mutations |
| title_short |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| title_full |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| title_fullStr |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| title_full_unstemmed |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| title_sort |
Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets |
| dc.creator.none.fl_str_mv |
Santos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638 Cruz, R. (R.) de la|||/items/0bf030f8-bd1d-45f1-9a7b-6015e79e71b5 Holst, C. (C.)|||/items/d9318459-9342-49cf-a2da-d6aeb6914a12 Grau, K. (K.)|||/items/dee32024-fa7a-4ab1-8273-3a025e0e73fc Naranjo, C. (C.)|||/items/9b345f66-f586-434d-84a8-02cfa612745e Maiz, A. (Alberto)|||/items/ceb4045f-526f-4f1b-9aa1-9ac32e034478 Astrup, A. (Arne)|||/items/f6a0e5d3-b236-40b9-a5a3-c380ae3446f2 Saris, W.H.M. (Wim H. M.)|||/items/72a768f2-c225-4139-86ea-e7895ef2a736 MacDonald, I. (Ian)|||/items/c1052005-3adc-4628-8276-f2803549627f Oppert, J.M. (Jean M.)|||/items/93cbce83-69c1-4820-9e4b-a4003c9c5629 Hansen, T. (Torben)|||/items/de8447d9-7fad-4ca8-9a14-fbe1493a5e91 Pedersen, O. (Oluf)|||/items/7f57f180-6e9b-44fd-914e-e2f48b9c94e7 Sørensen, T.I.A (Thorkild I. A.)|||/items/be862a34-8bb8-4755-ac24-3ed3689e43d0 Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131 |
| author |
Santos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638 |
| author_facet |
Santos, J.L. (José Luis)|||/items/b14e2212-42c2-440a-a236-430df8446638 Cruz, R. (R.) de la|||/items/0bf030f8-bd1d-45f1-9a7b-6015e79e71b5 Holst, C. (C.)|||/items/d9318459-9342-49cf-a2da-d6aeb6914a12 Grau, K. (K.)|||/items/dee32024-fa7a-4ab1-8273-3a025e0e73fc Naranjo, C. (C.)|||/items/9b345f66-f586-434d-84a8-02cfa612745e Maiz, A. (Alberto)|||/items/ceb4045f-526f-4f1b-9aa1-9ac32e034478 Astrup, A. (Arne)|||/items/f6a0e5d3-b236-40b9-a5a3-c380ae3446f2 Saris, W.H.M. (Wim H. M.)|||/items/72a768f2-c225-4139-86ea-e7895ef2a736 MacDonald, I. (Ian)|||/items/c1052005-3adc-4628-8276-f2803549627f Oppert, J.M. (Jean M.)|||/items/93cbce83-69c1-4820-9e4b-a4003c9c5629 Hansen, T. (Torben)|||/items/de8447d9-7fad-4ca8-9a14-fbe1493a5e91 Pedersen, O. (Oluf)|||/items/7f57f180-6e9b-44fd-914e-e2f48b9c94e7 Sørensen, T.I.A (Thorkild I. A.)|||/items/be862a34-8bb8-4755-ac24-3ed3689e43d0 Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131 |
| author_role |
author |
| author2 |
Cruz, R. (R.) de la|||/items/0bf030f8-bd1d-45f1-9a7b-6015e79e71b5 Holst, C. (C.)|||/items/d9318459-9342-49cf-a2da-d6aeb6914a12 Grau, K. (K.)|||/items/dee32024-fa7a-4ab1-8273-3a025e0e73fc Naranjo, C. (C.)|||/items/9b345f66-f586-434d-84a8-02cfa612745e Maiz, A. (Alberto)|||/items/ceb4045f-526f-4f1b-9aa1-9ac32e034478 Astrup, A. (Arne)|||/items/f6a0e5d3-b236-40b9-a5a3-c380ae3446f2 Saris, W.H.M. (Wim H. M.)|||/items/72a768f2-c225-4139-86ea-e7895ef2a736 MacDonald, I. (Ian)|||/items/c1052005-3adc-4628-8276-f2803549627f Oppert, J.M. (Jean M.)|||/items/93cbce83-69c1-4820-9e4b-a4003c9c5629 Hansen, T. (Torben)|||/items/de8447d9-7fad-4ca8-9a14-fbe1493a5e91 Pedersen, O. (Oluf)|||/items/7f57f180-6e9b-44fd-914e-e2f48b9c94e7 Sørensen, T.I.A (Thorkild I. A.)|||/items/be862a34-8bb8-4755-ac24-3ed3689e43d0 Martinez, J.A. (José Alfredo)|||/items/6a3581ea-897b-4439-a95c-19301775e131 |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Genome wide association Childhood obesity Eating behavior Food intake Body fat Polymorphisms Insulin Mutations |
| topic |
Genome wide association Childhood obesity Eating behavior Food intake Body fat Polymorphisms Insulin Mutations |
| description |
INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06), rs6014646-rs6024730 (p = 0.05) and rs3746619-rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans. |
| publishDate |
2011 |
| dc.date.none.fl_str_mv |
2011 2011-01-01 2011 2011-01-01 2013 2013-03-22 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/28170 |
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https://hdl.handle.net/10171/28170 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Public Library of Sciences |
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Public Library of Sciences |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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