Anti-Atherogenic Effects of Orlistat on Obesity-Induced Vascular Oxidative Stress Rat Model.

Zaidatul Akmal Othman,Mahaneem Mohamed,Joseph Bagi Suleiman,Zaida Zakaria,Wan Syaheedah Wan Ghazali

doi:10.3390/antiox10020251

Zaidatul Akmal Othman, Mahaneem Mohamed + Show 3 more

Open Access

https://doi.org/10.3390/antiox10020251

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Abstract

Obesity is typically linked to oxidative stress and inflammation, which lead to vascular damage and initiate the progression of atherosclerosis. The aim of this study was to determine the anti-atherosclerotic effect of orlistat on obesity-induced vascular oxidative stress in obese male rats. Twenty-four male Sprague–Dawley rats were categorized into two groups: normal (Normal group, n = 6) and high-fat diet (HFD group, n = 12). After six weeks, obese rats in the HFD group were administered either with distilled water (OB group) or orlistat 10 mg/kg/day (OB/OR group) for another six weeks. The OB group had a significant increase in lipid profiles (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)) and decrease in high-density lipoprotein (HDL) level compared to the Normal group. The aortic antioxidants enzymes activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and catalase (CAT)) as well as total glutathione (GSH) and total antioxidant capacity (TAC) of the OB group were significantly decreased compared to the Normal group. Furthermore, pro-inflammatory atherosclerotic markers (tumour necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1)) expressions were increased significantly, and anti-inflammatory marker (interleukin-10 (IL-10)) was decreased significantly in the OB group compared to the Normal group. Treatment with orlistat significantly improved lipid profile, increased antioxidant enzymes and expression of anti-inflammatory markers, and decreased the expression of the pro-inflammatory marker compared to the OB group. These findings may suggest the therapeutic effect of orlistat in attenuating the progression of the atherosclerotic stage in obesity.

Highlights

Obesity has been described as an excessive body fat deposition and may potentially risk the individual health
We previously reported that the supplementation of orlistat with concomitant high-fat diet (HFD) administration for six weeks had demonstrated its protective effects against the increased levels of total cholesterol (TC) and low-density lipoprotein (LDL) without changes in triglyceride (TG) and high-density lipoprotein (HDL) levels [15]
Our study has demonstrated the presence of increased adipocyte size in the OB group, which could be explained by the excess storage of fat from the HFD leading to the significant higher body weight gain compared to the Normal group

Summary

Introduction

Obesity has been described as an excessive body fat deposition and may potentially risk the individual health. Recent studies have proposed a pathological crosstalk between obesity, oxidative stress, and inflammatory process [3]. Antioxidants 2021, 10, 251 system to maintain and remove free radical, which further leads to pathological implication. This is further assessed by the presence of advanced oxidation product such as malondialdehyde (MDA) [4]. The oxidative modification has further taken place and converted the LDL into oxidative form [6]. This surges the rise of MDA formation, which prompts more macrophages to engulf the excess lipids as a part of a clearing process [6]

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