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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85131318634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85131318634&partnerID=8YFLogxK
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 -