SERPINE-1 May Help Predict Response to Gastric Sleeve Surgery, Study Suggests

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by Margarida Azevedo |

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surgery and SERPINE-1

Levels of a protein called SERPINE-1 and modifications in its gene may help predict the success of gastric sleeve surgery for obese patients seeking to lose weight and maintain their weight loss, a recent study suggests.

The study, titled “SERPINE-1 Gene Methylation and Protein as Molecular Predictors of Laparoscopic Sleeve Gastrectomy Outcome,” was published in the journal Obesity Surgery.

Bariatric surgery is an effective treatment for morbidly obese people, and gastric sleeve surgery or laparoscopic sleeve gastrectomy (LSG) has become one of the most commonly performed operations. LGS has been associated with weight loss and lessening of obesity-related conditions (comorbidities).

However, patients can be at risk for major complications and up to 15% do not end up losing weight. As such, predictors of surgery outcomes could help determine what treatment is better suited for each patient.

The SERPINE-1 protein, also known as plasminogen activator inhibitor 1 (PAI-1), has been associated with inflammation and may play a role in obesity and obesity-related comorbidities, previous studies suggest.

In fact, SERPINE-1 levels are reportedly affected after weight loss interventions, although the mechanisms in this process are yet to be elucidated.

Epigenetic changes are alterations in gene expression (and consequently protein levels) but not in the gene sequence itself. One such mechanism is DNA methylation, which has been associated with obesity, including methylation of SERPINE-1. Yet, the possible relationship between bariatric surgery and DNA methylation remains controversial (DNA methylation is the addition of a chemical group called methyl to DNA).

“[T]o the best of our knowledge, this is the first study to appraise the role of preoperative and six months postoperative levels of SERPINE-1 protein and its gene methylation as potential predictors for weight loss up to two years after LSG,” the researchers wrote.

The study also explored their relationship to obesity-associated inflammation, assessed via C-reactive protein (CRP) levels, and insulin resistance after surgery.

A total of 100 participants (age range 18–50) were enrolled in the study and then divided into two groups. The control group had 50 participants with normal weight, while the bariatric surgery group included 50 obese patients who underwent LSG.

This surgery resulted in significant weight loss at six months and continued until two years after surgery. Mean weight loss ranged from 24.57% at six months to 36.29% at two years after surgery.

Responders and non-responders to bariatric surgery were categorized according to mean average weight loss percentage. Those classified as responders achieved more than 24.57% weight loss at six months post-surgery.

Obese participants showed more inflammation and insulin resistance than controls. Six months after surgery, these markers were both significantly reduced but not normalized in obese patients.

The baseline SERPINE-1 protein and gene methylation levels were significantly higher in obese patients than in controls. Six months after LSG, the patients’ protein levels lowered significantly and were even normalized. However, gene methylation was still increased at this timepoint.

Researchers found that methylation state was significantly lower in responders versus non-responders, both at baseline and at six months after surgery. SERPINE-1 gene methylation post-surgery also correlated with CRP and insulin resistance levels.

In turn, SERPINE-1 protein levels after surgery were lower with greater weight loss, suggesting that this parameter could potentially predict weight loss maintenance after LSG.

“Baseline SERPINE-1 gene methylation might serve as a predictor to successful weight loss after LSG until a period of two years postoperatively. Meanwhile, postoperative SERPINE-1 protein might be a potential predictor for maintained weight loss after LSG,” the researchers wrote.

“Longer follow-up periods on a larger sample size might help to verify the predictive value of the studied biomarkers to weight loss maintenance after surgery,” they said. “Moreover, the predictive value of the studied biomarkers needs to be compared with different types of bariatric surgery.”

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