Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass: A Case–Control Study and Review of Literature

Gala, Khushboo; Ghusn, Wissam; Fansa, Sima; Dayyeh, Barham K. Abu; Ghanem, Omar M.; Kellogg, Todd A.; Acosta, Andrés

doi:10.1007/s11695-023-06462-0

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…A total of 30 genes previously related to the leptin-melanocortin pathway were sequenced by Sema4 Laboratories (Stamford, Connecticut) and have been detailed elsewhere. [8][9][10] The study was approved by the institutional review board of Mayo Clinic (18-010159). All participants provided prior written authorization for research use of their medical records and biologic samples, including use for genotyping studies.…”

Section: Methodsmentioning

confidence: 99%

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Leptin‐Melanocortin pathway variants and gastric emptying in patients with obesity

Cifuentes,

Ghusn,

Campos

et al. 2024

Neurogastroenterology Motil

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BackgroundAccelerated gastric emptying (GE) is a trait seen in obesity. Mutations in the hypothalamic leptin‐melanocortin 4 receptor (Leptin‐MC4R) pathway have been associated with obesity. We sought to investigate the association of leptin‐MC4R pathway variants and GE in patients with obesity.MethodsThis is a cross‐sectional study of patients with a history of severe obesity that were genotyped and completed a GE test by scintigraphy. We evaluated the percentage of GE (GE %) at 2 and 4 h between both groups using ANCOVA with weight and sex as covariates. We subdivide patients into carriers based on the location of the identified variants (i.e., upstream or downstream of the Leptin‐MC4R pathway) and compared them with noncarriers using ANOVA. Results are presented as mean and standard deviation (± SD).Key ResultsA total of 95 patients; nine carriers (67% females; 39.78 ± 12.33 years; BMI: 49.14 ± 12.96 kg/m2) and 86 noncarriers (87% female; 49.98 ± 13.74 years; BMI: 40.75 ± 6.29 kg/m2) were included. At 2 and 4 h, carriers had a delayed GE when compared noncarriers (p = 0.03 and p = 0.005, respectively). In carriers, when compared upstream carriers vs. downstream carriers vs. noncarriers by location there was a significant difference in GE among groups at 2 h and at 4 h (p = 0.02 and p = 0.01, respectively).Conclusions & InferencesCarriers of heterozygous variants in the Leptin‐MC4R pathway had a delayed GE compared to noncarriers. These findings point the important relationship between the Leptin‐MC4R pathway and gastric motility.

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Section: Methodsmentioning

confidence: 99%

“…A total of 30 genes previously related to the leptin‐melanocortin pathway were sequenced by Sema4 Laboratories (Stamford, Connecticut) and have been detailed elsewhere 8–10 . The study was approved by the institutional review board of Mayo Clinic (18–010159).…”

Section: Methodsmentioning

confidence: 99%

Leptin‐Melanocortin pathway variants and gastric emptying in patients with obesity

Cifuentes,

Ghusn,

Campos

et al. 2024

Neurogastroenterology Motil

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“…With a broader overview of mutations affecting components along the MC4R pathway, a study included 50 carriers, who were matched based on sex, age, BMI, and years since surgery with 100 non-carriers. 122,123 The study showed that individuals with heterozygous variants experienced progressive and significant weight regain in the mid and long term following RYGB. Similarly, in a case-control study analysing outcomes of transoral outlet reduction due to weight regain after RYGB, carriers exhibited decreased weight loss after undergoing this procedure.…”

Section: Bariatric Surgerymentioning

confidence: 99%

“…The study showed that individuals with heterozygous variants experienced progressive and significant weight regain in the mid and long term following RYGB. Similarly, in a case–control study analysing outcomes of transoral outlet reduction due to weight regain after RYGB, carriers exhibited decreased weight loss after undergoing this procedure 124 . Further studies are needed to enhance our understanding of the underlying pathophysiology contributing to variations, if any, in outcomes among patients with genetic obesity, enabling informed treatment decisions and establishment of standardized outcomes.…”

Section: Treatment Of Monogenic Obesitymentioning

confidence: 99%

The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

Fansa,

Acosta

2024

Diabetes Obesity Metabolism

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Over the past few decades, there has been a global surge in the prevalence of obesity, rendering it a globally recognized epidemic. Contrary to simply being a medical condition, obesity is an intricate disease with a multifactorial aetiology. Understanding the precise cause of obesity remains a challenge; nevertheless, there seems to be a complex interplay among biological, psychosocial and behavioural factors. Studies on the genetic factors of obesity have revealed several pathways in the brain that play a crucial role in food intake regulation. The best characterized pathway, thus far, is the leptin–melanocortin pathway, from which disruptions are responsible for the majority of monogenic obesity disorders. The effectiveness of conservative lifestyle interventions in addressing monogenic obesity has been limited. Therefore, it is crucial to complement the management strategy with pharmacological and surgical options. Emphasis has been placed on developing drugs aimed at replacing the absent signals, with the goal of restoring the pathway. In both monogenic and polygenic forms of obesity, outcomes differ across various interventions, likely due to the multifaceted nature of the disease. This underscores the need to explore alternative therapeutic strategies that can mitigate this heterogeneity. Precision medicine can be regarded as a powerful tool that can address this concern, as it values the understanding of the underlying abnormality triggering the disease and provides a tailored treatment accordingly. This would assist in optimizing outcomes of the current therapeutic approaches and even aid in the development of novel treatments capable of more effectively managing the global obesity epidemic.

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The Effect of Heterozygous Gene Variants of the Leptin-Melanocortin Pathway on Weight Loss Following Sleeve Gastrectomy

Feris,

Ghusn,

Campos

et al. 2023

OBES SURG

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Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass: A Case–Control Study and Review of Literature

Cited by 8 publications

References 15 publications

Leptin‐Melanocortin pathway variants and gastric emptying in patients with obesity

Leptin‐Melanocortin pathway variants and gastric emptying in patients with obesity

The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management

The Effect of Heterozygous Gene Variants of the Leptin-Melanocortin Pathway on Weight Loss Following Sleeve Gastrectomy

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