Beneficial Effect of Bariatric Surgery on Abnormal MMP-9 and AMPK Activities: Potential Markers of Obesity-Related CV Risk.

Concha F García-Prieto,Andrés Sanchez-Pernaute,Beatriz Somoza,Miguel A Rubio,Elena Vega-Martín,Elena Bordiú,Antonio Torres,David Ramiro-Cortijo,Miriam Martín-Ramos,Marta Gil-Ortega,María Fernández-Alfonso,I Aránguez

doi:10.3389/fphys.2019.00553

Abstract

Bariatric surgery (BS) results in sustained weight loss and may reverse inflammation, metabolic alterations, extracellular matrix remodeling and arterial stiffness. We hypothesize that increased stiffening in omental arteries from obese patients might be associated with an increase in MMP activity and a decrease in p-AMPK, together with systemic oxidative stress and inflammation. Moreover, BS could contribute to reversing these alterations. This study was conducted with 38 patients of Caucasian origin: 31 adult patients with morbid obesity (9 men and 22 women; mean age 46 years and BMI = 42.7 ± 1.0 kg/m2) and 7 non-obese subjects (7 women; mean age 45 years and BMI = 22.7 ± 0.6 kg/m2). Seventeen obese patients were studied before and 12 months after BS. The stiffness index β, an index of intrinsic arterial stiffness, was determined in omental arteries and was significantly higher in obese patients. Levels of phosphorylated AMPK (p-AMPKThr-172) and SIRT-1 were significantly lower in peripheral blood mononuclear cells (PBMCs) from obese patients than those from non-obese patients (p < 0.05) and were normalized after BS. Total and active MMP-9 activities, LDH, protein carbonyls and uric acid were higher in obese patients and reduced by BS. Moreover, there was a correlation between plasmatic LDH levels and the stiffness index β. BS has a beneficial effect on abnormal MMP-9, LDH and AMPK activities that might be associated with the development of arterial stiffness in obese patients. Since these parameters are easily measured in blood samples, they could constitute potential biomarkers of cardiovascular risk in morbid obesity.

Highlights

Obesity constitutes a major social problem worldwide and is associated with insulin resistance, diabetes, and a higher risk of cardiovascular disease (CVD) (Morris, 2008)
In the pre-surgery group, 14 (82.4%) patients were diagnosed with type 2 diabetes mellitus (T2DM, 76.5% treated with metformin therapy), (58.8%) with hypertension and (64.7%) with dyslipidemia
In the non-surgery group, no patient was diagnosed with T2DM, 8 (57.1%) patients were diagnosed with hypertension and 9 (64.3%) with dyslipidemia

Summary

Introduction

Obesity constitutes a major social problem worldwide and is associated with insulin resistance, diabetes, and a higher risk of cardiovascular disease (CVD) (Morris, 2008). Body fat and central adiposity have been suggested as predictors of accelerated arterial stiffness that develops at younger ages in obese patients (Nemes et al, 2008; Grassi and Diez, 2009; Kangas et al, 2013; Brunner et al, 2015; Satoh-Asahara et al, 2015). Stiffness index β, obtained from the stress–strain relationship (Dobrin, 1978), is currently a well-accepted marker of intrinsic arterial stiffness and it has been determined in several studies performed in human resistance arteries (Savoia et al, 2008; Fonck et al, 2009; Grassi et al, 2010). The increase of intrinsic stiffness of large arteries is considered an independent predictor of cardiovascular (CV) diseases (Bouissou et al, 2014) and precedes changes in systemic arterial stiffness (Sehgel et al, 2013)

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