Abstract
Matrix metalloproteinases (MMP) and their endogenous inhibitor, the tissue inhibitor of metalloproteinases (TIMP), are expressed in many different cell types and play an important role in physiologic and pathological degradation of extracellular matrix (ECM). Starting from these observations and considering the activation state of peripheral blood mononuclear cells (PBMCs) in obesity, we investigated the gene expression of metalloproteinases before and after Roux-en-Y gastric bypass (RYBG). The study was performed in the Ribeirão Preto Medical School University Hospital. Seventy-three women were divided into a study group (SG), composed of 53 individuals with severe obesity before and after 6 months of RYGB, and a control group (CG), composed of 20 normal-weight individuals. Anthropometric and body composition data were collected, and peripheral blood for ribonucleic acid (RNA) extraction. The biological samples were submitted to a quantitative real-time polymerase chain reaction to evaluate the expression of MMP2 and TIMP2 genes. Alterations in weight loss, body mass index (BMI), and fat mass (FM) were observed after 6 months of RYGB (p < 0.05). A reduction of gene expression of TIMP2 was observed after 6 months of RYGB, contributing positively to the weight loss (R2 = 0.33 p = 0.04). The enrichment analyses highlighted the interaction between TIMP2 and MMP2 genes and the molecular pathways involving the ECM remodeling in the obesity condition. RYGB contributes significantly to weight loss, improved BMI, reduced FM, and reduced TIMP2 expression in PBMCs, which might contribute to the ECM remodeling in the obesity and could be useful as a circulating biomarker.
Highlights
Obesity is one of the most critical public health problems, and the prevalence has reached epidemic proportions worldwide [1, 2]
extracellular matrix (ECM) is composed of several components, including matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), that play an essential role in the ECM remodeling and adipose tissue function [4]
In study group (SG), we did not find a correlation for these genes pre-RYGB (Supplementary Figure 1B), but interestingly, after RYGB, we found a positive correlation between tissue inhibitor of metalloproteinases 2 (TIMP2) and matrix metalloproteinases2 (MMP2) as observed in control group (CG) (Supplementary Figure 1C)
Summary
Obesity is one of the most critical public health problems, and the prevalence has reached epidemic proportions worldwide [1, 2]. According to the World Health Organization (WHO), obesity is defined as “abnormal or excessive adipose tissue accumulation that offers a risk to health” [2]. In the development of overweight and obesity, adipose tissue is changed with hypertrophic adipocytes, infiltration of macrophages, and other pro-inflammatory immune cells. The occurrence of the extracellular matrix (ECM) dynamic remodeling is fundamental for the expansion of the adipose tissue to allow necessary and proper structural changes [3]. ECM is composed of several components, including matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), that play an essential role in the ECM remodeling and adipose tissue function [4]. Circulating levels of TIMP-1 and -2 are increased in patients with metabolic syndrome and type 2 diabetes (T2D), while MMPs imbalance is associated with obesity and T2D [4]
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