Relationship between the Plasma Proteome and Changes in Inflammatory Markers after Bariatric Surgery.

Helene A Fachim,Zohaib Iqbal,Antony Whetton,Rachelle P Donn,Handrean Soran,Akheel A Syed,Ivona Baricevic-Jones,Bethany Geary,J Martin Gibson,Adrian H Heald,Amy E Campbell

doi:10.3390/cells10102798

Abstract

Severe obesity is a disease associated with multiple adverse effects on health. Metabolic bariatric surgery (MBS) can have significant effects on multiple body systems and was shown to improve inflammatory markers in previous short-term follow-up studies. We evaluated associations between changes in inflammatory markers (CRP, IL6 and TNFα) and circulating proteins after MBS. Methods: Sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics was performed on plasma samples taken at baseline (pre-surgery) and 6 and 12 months after MBS, and concurrent analyses of inflammatory/metabolic parameters were carried out. The change in absolute abundances of those proteins, showing significant change at both 6 and 12 months, was tested for correlation with the absolute and percentage (%) change in inflammatory markers. Results: We found the following results: at 6 months, there was a correlation between %change in IL-6 and fold change in HSPA4 (rho = −0.659; p = 0.038) and in SERPINF1 (rho = 0.714, p = 0.020); at 12 months, there was a positive correlation between %change in IL-6 and fold change in the following proteins—LGALS3BP (rho = 0.700, p = 0.036), HSP90B1 (rho = 0.667; p = 0.05) and ACE (rho = 0.667, p = 0.05). We found significant inverse correlations at 12 months between %change in TNFα and the following proteins: EPHX2 and ACE (for both rho = −0.783, p = 0.013). We also found significant inverse correlations between %change in CRP at 12 months and SHBG (rho = −0.759, p = 0.029), L1CAM (rho = −0.904, p = 0.002) and AMBP (rho = −0.684, p = 0.042). Conclusion: Using SWATH-MS, we identified several proteins that are involved in the inflammatory response whose levels change in patients who achieve remission of T2DM after bariatric surgery in tandem with changes in IL6, TNFα and/or CRP. Future studies are needed to clarify the underlying mechanisms in how MBS decreases low-grade inflammation.

Highlights

Obesity is recognized as the fastest growing problem affecting public health worldwide and has many consequences [1,2,3]
The list of proteins that correlated with inflammatory markers in relation to fold change at specific time points are shown on Table 2
L1 cell adhesion molecule (L1CAM) and sex hormone-binding globulin (SHBG) levels increased while heat shock protein 90 Beta family member 1 (HSP90B1) and heat shock protein 4 (HSPA4) levels fell

Summary

Introduction

Obesity is recognized as the fastest growing problem affecting public health worldwide and has many consequences [1,2,3]. The obese phenotype results in a chronic low-grade inflammatory state characterized by the putative secretion of pro-inflammatory markers by adipocytes [8], including those that may contribute to the inflammatory component in the development of. Metabolic bariatric surgery (MBS) results in metabolic pathway recalibration, which phenotypically can manifest as early remission of T2DM in the days following surgery before any appreciable weight loss has occurred [12]. Immediate post-operative weight-independent hormonal changes combined with ensuing weight loss can result in remission of T2DM in up to 80% of patients after one year [14]. MBS results in major metabolic changes and there remain many questions as to the metabolic and inflammatory pathways that are changed following MBS, with significant consequences for health outcomes and how biological phenotype pre-MBS may relate to outcomes post-MBS

Methods

Results

Discussion

Conclusion