Serum proteome changes and accelerated reduction of fat mass after laparoscopic gastric plication in morbidly obese patients

Laparoscopic Gastric Plication (LGP) is a relatively new bariatric surgical procedure which no part of the stomach is removed. It is not clearly understood how LGP leads to fatty tissue reduction. We aimed to investigate the impact of LGP on serum proteome and understand molecular mechanisms of LGP-induced weight loss post-surgery. A Prospective observational study of 16 obese individuals who underwent LGP was performed. A Label-free quantitative shotgun proteomics approach was used to compare serum proteome of subjects before surgery with serum of the same individuals 1 to 2 months post-surgery (T1) and 4 to 5 months post-surgery (T2). The proteome analysis revealed that 48 proteins were differentially regulated between pre-surgery and T1, and seven proteins between pre-surgery and T2 of which six proteins were shared between the two timepoints. Among differentially regulated proteins, four proteins (SRGN, FETUB, LCP1 and CFP) have not previously been described in the context of BMI/weight loss. Despite few differences following LGP, most regulated serum proteins are in accordance with alternative weight loss procedures. Pathway analysis revealed changes to lipid- and inflammatory pathways, including PPARα/RXRα, LXR/RXR and FXR/RXR activation, especially at T1. At T2, the pathways related to inflammation and immune system are most affected. SIGNIFICANCE: Among the available clinical therapies for morbid obesity, bariatric surgery is considered as the most effective approach to achieve long-term weight loss, alongside a significant improvement in metabolic syndrome. However, very little is known about the underlying mechanism associated with significant weight loss post-surgery. Understanding such mechanisms could lead to development of safer non-surgical weight loss approaches. We here present the first analysis of the impact of LGP on the serum proteome, to bring new insights into the underlying molecular mechanism. Our findings indicate that LGP has a comprehensive systemic effect based on the blood serum proteome profile which might account for accelerated reduction of fat mass after surgery, thus, food restriction is not the only reason for weight loss following this unique surgical approach. As secretory regions of the stomach are preserved in LGP and it is associated with minimal physiological and anatomical changes, the findings are of high importance in the field of bariatric surgery and weight loss.