TY - JOUR
T1 - Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Roux-en-Y Gastric Bypass Outcomes
T2 - a 15-Year Case–Control Study
AU - Campos, Alejandro
AU - Cifuentes, Lizeth
AU - Hashem, Anas
AU - Busebee, Bradley
AU - Hurtado-Andrade, Maria D.
AU - Ricardo-Silgado, Maria L.
AU - McRae, Alison
AU - De la Rosa, Alan
AU - Feris, Fauzi
AU - Bublitz, Joshua T.
AU - Hensrud, Donald
AU - Camilleri, Michael
AU - Kellogg, Todd A.
AU - Eckel-Passow, Jeanette E.
AU - Olson, Janet
AU - Acosta, Andres
N1 - Funding Information:
This study was funded by the NIH (NIH K23-DK114460) and The Mayo Clinic Biobank, Mayo Clinic Center for Individualized Medicine. Genotyping studies were provided by Rhythm Pharmaceuticals. The funding sources were not involved in the study design, in the collection, analysis, and interpretation of the data, in writing the report, or in the decision to submit the paper for publication.
Funding Information:
We thank the participants from the Mayo Clinic Biobank and Rhythm Pharmaceuticals for the genotyping studies.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/8
Y1 - 2022/8
N2 - Introduction: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. Methods: In this matched case–control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. Results: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was − 16.6 ± 10.7 compared with − 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower − 32.1 ± 8.1 in carriers compared with − 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). Conclusions: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery. Graphical abstract: [Figure not available: see fulltext.].
AB - Introduction: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. Methods: In this matched case–control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. Results: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was − 16.6 ± 10.7 compared with − 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower − 32.1 ± 8.1 in carriers compared with − 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). Conclusions: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery. Graphical abstract: [Figure not available: see fulltext.].
KW - Genetic obesity
KW - Leptin-melanocortin pathway
KW - Roux-en-Y gastric bypass surgery
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U2 - 10.1007/s11695-022-06122-9
DO - 10.1007/s11695-022-06122-9
M3 - Article
C2 - 35654930
AN - SCOPUS:85131318634
SN - 0960-8923
VL - 32
SP - 2632
EP - 2640
JO - Obesity Surgery
JF - Obesity Surgery
IS - 8
ER -