Unit of Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia.
Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.
Int J Mol Sci. 2022 Sep 6;23(18):10266. doi: 10.3390/ijms231810266.
Oxidative stress contributes to major complications of obesity. This study intended to identify whether orlistat could mitigate myocardial damage in obese animal models. The tested rats were divided into two groups and fed either with normal chow ( = 6 per group) or with a high-fat diet (HFD) for 6 weeks to induce obesity ( = 12 per group). Obese rats were further subjected to treatment either with distilled water (OB group) or orlistat 10 mg/kg/day (OB + OR group). Key indices of oxidative stress, inflammation, and apoptosis were assessed using an immunohistochemical-based technique and real-time PCR. The OB group showed significant increases of oxidative stress markers (TBARs and PCO), with significant decreases of anti-oxidant markers (Nrf2, SOD, CAT, and GPx). Furthermore, mRNA expression of pro-inflammatory markers (TNF-α and NF-κβ) and pro-apoptosis markers (Bax, Caspase-3, Caspase-8, and Caspase-9) were significantly upregulated in the OB group. Obese rats developed pathological changes of myocardial damages as evidenced by the presence of myocardial hypertrophy and inflammatory cells infiltration. Orlistat dampened the progression of myocardial damage in obese rats by ameliorating the oxidative stress, and by inhibiting NF-κβ pathway and caspase-dependent cell apoptosis. Our study proposed that orlistat could potentially mitigate oxidative stress-linked myocardial damage by mitigating inflammation and apoptosis, thus rationalizing its medical usage.
氧化应激是肥胖的主要并发症之一。本研究旨在探讨奥利司他是否可以减轻肥胖动物模型的心肌损伤。将实验大鼠分为两组，分别给予普通饲料（每组 6 只）或高脂饲料（HFD，每组 12 只）喂养 6 周以诱导肥胖。肥胖大鼠进一步给予蒸馏水（OB 组）或奥利司他 10mg/kg/天（OB+OR 组）治疗。采用免疫组化和实时 PCR 技术检测氧化应激、炎症和细胞凋亡的关键指标。OB 组的氧化应激标志物（TBARs 和 PCO）显著增加，抗氧化标志物（Nrf2、SOD、CAT 和 GPx）显著减少。此外，OB 组促炎标志物（TNF-α和 NF-κβ）和促凋亡标志物（Bax、Caspase-3、Caspase-8 和 Caspase-9）的 mRNA 表达也显著上调。肥胖大鼠出现心肌损伤的病理变化，表现为心肌肥大和炎症细胞浸润。奥利司他通过改善氧化应激、抑制 NF-κβ 通路和半胱天冬酶依赖性细胞凋亡，减轻肥胖大鼠的心肌损伤进展。本研究表明，奥利司他通过减轻炎症和细胞凋亡，可能减轻与氧化应激相关的心肌损伤，从而为其在医学上的应用提供了合理依据。
