Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions
The loss of function melanocortin 4-receptor (<i>MC4R</i>) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown...
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MDPI AG
2022-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/12/2267 |
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| author | Itzel G. Salazar-Valencia Hugo Villamil-Ramírez Francisco Barajas-Olmos Martha Guevara-Cruz Luis R. Macias-Kauffer Humberto García-Ortiz Omar Hernández-Vergara David Alberto Díaz de Sandy-Galán Paola León-Mimila Federico Centeno-Cruz Luis E. González-Salazar Rocío Guizar-Heredia Edgar Pichardo-Ontiveros Leonor Jacobo-Albavera Rosalinda Posadas-Sánchez Gilberto Vargas-Alarcón Rafael Velazquez-Cruz Ruth Gutiérrez-Aguilar Carlos Zerrweck Héctor Isaac Rocha-González Juan Gerardo Reyes-García Miriam del C. Carrasco-Portugal Francisco Javier Flores-Murrieta Armando R. Tovar Lorena Orozco Teresa Villarreal-Molina Samuel Canizales-Quinteros |
| author_facet | Itzel G. Salazar-Valencia Hugo Villamil-Ramírez Francisco Barajas-Olmos Martha Guevara-Cruz Luis R. Macias-Kauffer Humberto García-Ortiz Omar Hernández-Vergara David Alberto Díaz de Sandy-Galán Paola León-Mimila Federico Centeno-Cruz Luis E. González-Salazar Rocío Guizar-Heredia Edgar Pichardo-Ontiveros Leonor Jacobo-Albavera Rosalinda Posadas-Sánchez Gilberto Vargas-Alarcón Rafael Velazquez-Cruz Ruth Gutiérrez-Aguilar Carlos Zerrweck Héctor Isaac Rocha-González Juan Gerardo Reyes-García Miriam del C. Carrasco-Portugal Francisco Javier Flores-Murrieta Armando R. Tovar Lorena Orozco Teresa Villarreal-Molina Samuel Canizales-Quinteros |
| author_sort | Itzel G. Salazar-Valencia |
| collection | DOAJ |
| description | The loss of function melanocortin 4-receptor (<i>MC4R</i>) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), <i>p</i> = 0.005]. Regarding interventions, in the dietary restriction group only two patients were <i>MC4R</i> Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single <i>MC4R</i> loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional <i>MC4R</i> allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in <i>MC4R</i> Ile269Asn mutation carriers. |
| first_indexed | 2024-03-09T16:29:37Z |
| format | Article |
| id | doaj.art-9808d9e3722348d58bcd768de68b77f1 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T16:29:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9808d9e3722348d58bcd768de68b77f12023-11-24T15:03:55ZengMDPI AGGenes2073-44252022-12-011312226710.3390/genes13122267Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery InterventionsItzel G. Salazar-Valencia0Hugo Villamil-Ramírez1Francisco Barajas-Olmos2Martha Guevara-Cruz3Luis R. Macias-Kauffer4Humberto García-Ortiz5Omar Hernández-Vergara6David Alberto Díaz de Sandy-Galán7Paola León-Mimila8Federico Centeno-Cruz9Luis E. González-Salazar10Rocío Guizar-Heredia11Edgar Pichardo-Ontiveros12Leonor Jacobo-Albavera13Rosalinda Posadas-Sánchez14Gilberto Vargas-Alarcón15Rafael Velazquez-Cruz16Ruth Gutiérrez-Aguilar17Carlos Zerrweck18Héctor Isaac Rocha-González19Juan Gerardo Reyes-García20Miriam del C. Carrasco-Portugal21Francisco Javier Flores-Murrieta22Armando R. Tovar23Lorena Orozco24Teresa Villarreal-Molina25Samuel Canizales-Quinteros26Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoLaboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoDepartmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoLaboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoLaboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoDepartmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoDepartmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoLaboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoDepartamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez (INCICh), Mexico City 14080, MexicoDepartamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez (INCICh), Mexico City 14080, MexicoLaboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoLaboratorio de Enfermedades Metabólicas: Obesidad y Diabetes, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Hospital Infantil de México “Federico Gómez”, Mexico City 06720, MexicoClínica de Obesidad del Hospital General Tláhuac, Mexico City 13250, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, MexicoUnidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, MexicoDepartmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, MexicoLaboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoLaboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, MexicoUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City 14610, MexicoThe loss of function melanocortin 4-receptor (<i>MC4R</i>) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), <i>p</i> = 0.005]. Regarding interventions, in the dietary restriction group only two patients were <i>MC4R</i> Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single <i>MC4R</i> loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional <i>MC4R</i> allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in <i>MC4R</i> Ile269Asn mutation carriers.https://www.mdpi.com/2073-4425/13/12/2267melanocortin-4-receptorIle269Asn-mutationobesityweight-lossinterventions |
| spellingShingle | Itzel G. Salazar-Valencia Hugo Villamil-Ramírez Francisco Barajas-Olmos Martha Guevara-Cruz Luis R. Macias-Kauffer Humberto García-Ortiz Omar Hernández-Vergara David Alberto Díaz de Sandy-Galán Paola León-Mimila Federico Centeno-Cruz Luis E. González-Salazar Rocío Guizar-Heredia Edgar Pichardo-Ontiveros Leonor Jacobo-Albavera Rosalinda Posadas-Sánchez Gilberto Vargas-Alarcón Rafael Velazquez-Cruz Ruth Gutiérrez-Aguilar Carlos Zerrweck Héctor Isaac Rocha-González Juan Gerardo Reyes-García Miriam del C. Carrasco-Portugal Francisco Javier Flores-Murrieta Armando R. Tovar Lorena Orozco Teresa Villarreal-Molina Samuel Canizales-Quinteros Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions Genes melanocortin-4-receptor Ile269Asn-mutation obesity weight-loss interventions |
| title | Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions |
| title_full | Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions |
| title_fullStr | Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions |
| title_full_unstemmed | Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions |
| title_short | Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions |
| title_sort | effect of the melanocortin 4 receptor ile269asn mutation on weight loss response to dietary phentermine and bariatric surgery interventions |
| topic | melanocortin-4-receptor Ile269Asn-mutation obesity weight-loss interventions |
| url | https://www.mdpi.com/2073-4425/13/12/2267 |
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