Bariatric Surgery Appears Effective for Obesity Linked to Mutations, Study Says

Bariatric Surgery Appears Effective for Obesity Linked to Mutations, Study Says

Having a genetic cause of obesity does not lessen the efficacy of bariatric surgery as a way of losing weight, a study reports.

Although this study suggests equal effectiveness for this surgery in obese patients with and without a genetic cause, weight loss was lesser in people with mutations in the MC4R gene who underwent sleeve gastrectomy.

The study, “Genetic Obesity and Bariatric Surgery Outcome in 1014 Patients with Morbid Obesity,” was published in the journal Obesity Surgery.

Mutations in a key pathway regulating hunger — the melanocortin-4 receptor (MC4R) pathway — are a known cause of genetic obesity, including leptin receptor (LEPR) and proopiomelanocortin (POMC) deficiencies, as well as Prader-Willi syndrome.

Bariatric surgery, an intervention that makes the stomach smaller or changes the small intestine, is the most effective treatment option for obesity in adults.

However, for reasons yet to be determined, 20%–30% of the patients do not lose enough weight or even regain weight after the procedure. Possible explanations include anatomical changes and an inability to permanently adopt a healthy lifestyle.

Another potential reason is carrying an underlying mutation, which could make it difficult to lose weight. But little is known about the prevalence of MC4R-related mutations and their effect on weight loss after bariatric surgery.

Researchers addressed this gap by studying 1,014 adults with morbid obesity. All underwent bariatric surgery at Rijnstate Hospital Arnhem/Vitalys in the Netherlands. Gastric bypass, also called Roux-en-Y gastric bypass, and sleeve gastrectomy were both conducted by laparoscopy, a minimally invasive procedure compared to open surgery.

Specifically, gastric bypass creates a small pouch in the upper section of the stomach and connects it to the small intestine. For sleeve gastrectomy, the surgeon removes most of the stomach, leaving only a tube-shaped section about the size and shape of a banana. Both procedures make the stomach smaller, restricting the amount of food a person is able to eat.

These surgical procedures, particularly gastric bypass, also change some gut hormones and other factors that may affect appetite and metabolism, and help in losing weight.

Researchers found that 30 patients (3%) had genetic obesity, caused by mutations in either MC4RPOMCPCSK1SIM1, or the PTEN gene. Their mean body mass index (BMI) was 48.3 kg/m2. Among the 827 patients without molecular diagnosis (controls), mean BMI was 45.6 kg/m2.

One and two years after having their first gastric bypass surgery, patients with mutations in MC4R, POMC, or PCSK1 lost an amount of weight equivalent to that lost in those without confirmed genetic obesity.

As to sleeve gastrectomy, the average weight loss in the three patients with obesity caused by MC4R gene mutations was 19.3% at one year and 9.5% at two years after surgery. These were the only cases where patients with genetic obesity lost less weight compared to those not diagnosed with genetic obesity. It also shows superior weight loss after initial gastric bypass than after sleeve gastrectomy in people with MC4R mutations.

Overall, apart from patients with MC4R mutations having sleeve gastrectomy, findings show “weight loss was comparable between patients with or without a molecular diagnosis after 2 years of follow-up,” the researchers wrote.

“[M]utations in POMC and PCSK1 do not interfere with the effectiveness of most commonly performed bariatric procedures within the first 2 years of follow-up,” they added.

However, a longer follow-up and a larger group of patients are needed to better assess the durability of weight loss in this patient population.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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