The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation
We report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41–82 kg/m<sup>2</sup>), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/5/430 |
| _version_ | 1797497958895190016 |
|---|---|
| author | Ronit Grinbaum Nahum Beglaibter Stella Mitrani-Rosenbaum Lee M. Kaplan Danny Ben-Zvi |
| author_facet | Ronit Grinbaum Nahum Beglaibter Stella Mitrani-Rosenbaum Lee M. Kaplan Danny Ben-Zvi |
| author_sort | Ronit Grinbaum |
| collection | DOAJ |
| description | We report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41–82 kg/m<sup>2</sup>), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All patients had similar sociodemographic backgrounds and were followed for an average of 7 years. Three of the four homozygous patients regained their full weight (42–77 kg/m<sup>2</sup>), while the fourth lost weight but remained obese with a body mass index of 60 kg/m<sup>2</sup>. Weight regain was associated with relapse of most comorbidities, yet hyperglycemia did not relapse or was delayed. A1c levels were reduced in homozygous and heterozygous patients. The long-term follow-up data on this very unique genetic setting show that weight loss and amelioration of obesity following bariatric surgery require active MC4R signaling, while the improvement in glycemia is in part independent of weight loss. The study validates animal models and demonstrates the importance of biological signaling in the regulation of weight, even after bariatric surgery. |
| first_indexed | 2024-03-10T03:26:35Z |
| format | Article |
| id | doaj.art-fde35e1cca4b4244a8bf5b3a185f58f4 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T03:26:35Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-fde35e1cca4b4244a8bf5b3a185f58f42023-11-23T12:07:19ZengMDPI AGMetabolites2218-19892022-05-0112543010.3390/metabo12050430The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function MutationRonit Grinbaum0Nahum Beglaibter1Stella Mitrani-Rosenbaum2Lee M. Kaplan3Danny Ben-Zvi4Department of Surgery, Hadassah University Hospital Mount Scopus and the Hebrew University-Hadassah Medical School, Jerusalem 91240, IsraelDepartment of Surgery, Hadassah University Hospital Mount Scopus and the Hebrew University-Hadassah Medical School, Jerusalem 91240, IsraelGoldyne Savad Institute of Gene Therapy, Hebrew University-Hadassah Medical School, Jerusalem 91120, IsraelObesity, Metabolism and Nutrition Institute, Massachusetts General Hospital, Boston, MA 02114, USADepartment of Developmental Biology and Cancer Research, Institute of Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, IsraelWe report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41–82 kg/m<sup>2</sup>), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All patients had similar sociodemographic backgrounds and were followed for an average of 7 years. Three of the four homozygous patients regained their full weight (42–77 kg/m<sup>2</sup>), while the fourth lost weight but remained obese with a body mass index of 60 kg/m<sup>2</sup>. Weight regain was associated with relapse of most comorbidities, yet hyperglycemia did not relapse or was delayed. A1c levels were reduced in homozygous and heterozygous patients. The long-term follow-up data on this very unique genetic setting show that weight loss and amelioration of obesity following bariatric surgery require active MC4R signaling, while the improvement in glycemia is in part independent of weight loss. The study validates animal models and demonstrates the importance of biological signaling in the regulation of weight, even after bariatric surgery.https://www.mdpi.com/2218-1989/12/5/430obesitybariatric surgerydiabetesOSAmelanocortin 4 receptor |
| spellingShingle | Ronit Grinbaum Nahum Beglaibter Stella Mitrani-Rosenbaum Lee M. Kaplan Danny Ben-Zvi The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation Metabolites obesity bariatric surgery diabetes OSA melanocortin 4 receptor |
| title | The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation |
| title_full | The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation |
| title_fullStr | The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation |
| title_full_unstemmed | The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation |
| title_short | The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation |
| title_sort | obesogenic and glycemic effect of bariatric surgery in a family with a melanocortin 4 receptor loss of function mutation |
| topic | obesity bariatric surgery diabetes OSA melanocortin 4 receptor |
| url | https://www.mdpi.com/2218-1989/12/5/430 |
| work_keys_str_mv | AT ronitgrinbaum theobesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT nahumbeglaibter theobesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT stellamitranirosenbaum theobesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT leemkaplan theobesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT dannybenzvi theobesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT ronitgrinbaum obesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT nahumbeglaibter obesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT stellamitranirosenbaum obesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT leemkaplan obesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation AT dannybenzvi obesogenicandglycemiceffectofbariatricsurgeryinafamilywithamelanocortin4receptorlossoffunctionmutation |