Bochi Ana Paula Garcia, Ferreira Guilherme da Silva, Del Bianco Vanessa, Pinto Paula Ramos, Rodrigues Letícia Gomes, Trevisani Mayara da Silva, Furukawa Luzia Naoko Shinohara, Bispo Kely Cristina Soares, da Silva Alexandre Alves, Velosa Ana Paula Pereira, Nakandakare Edna Regina, Machado Ubiratan Fabres, Teodoro Walcy Paganelli Rosolia, Passarelli Marisa, Catanozi Sergio
Laboratorio de Lipides (LIM-10), Hospital das Clinicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246 000, Brazil.
Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of Medicine, University of São Paulo, São Paulo 01246 000, Brazil.
Antioxidants (Basel). 2022 Oct 13;11(10):2023. doi: 10.3390/antiox11102023.
This study investigated the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet. LDL receptor knockout (LDLR KO) mice were fed a low-sodium (LS) (0.15% NaCl) or normal-sodium (NS; 1.27% NaCl) diet, submitted to AET in a treadmill, 5 times/week, 60 min/day, 15 m/min, for 90 days, or kept sedentary. Blood pressure (BP), plasma total cholesterol (TC) and triglyceride (TG) concentrations, lipoprotein profile, and insulin sensitivity were evaluated at the end of the AET protocol. Lipid infiltration, angiotensin II type 1 receptor (AT1), receptor for advanced glycation end products (RAGE), carboxymethyllysine (CML), and 4-hydroxynonenal (4-HNE) contents as well as gene expression were determined in the brachiocephalic trunk. BP and TC and gene expression were similar among groups. Compared to the NS diet, the LS diet increased vascular lipid infiltration, CML, RAGE, 4-HNE, plasma TG, LDL-cholesterol, and VLDL-TG. Conversely, the LS diet reduced vascular AT1 receptor, insulin sensitivity, HDL-cholesterol, and HDL-TG. AET prevented arterial lipid infiltration; increases in CML, RAGE, and 4-HNE contents; and reduced AT1 levels and improved LS-induced peripheral IR. The current study showed that AET counteracted the deleterious effects of chronic LS diet in an atherogenesis-prone model by ameliorating peripheral IR, lipid infiltration, CML, RAGE, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk. These events occurred independently of the amelioration of plasma-lipid profile, which was negatively affected by the severe dietary-sodium restriction.
本研究调查了有氧运动训练（AET）在预防严重低钠（LS）饮食诱导的血脂异常、胰岛素抵抗（IR）和动脉粥样硬化形成方面的效果。给低密度脂蛋白受体敲除（LDLR KO）小鼠喂食低钠（LS）（0.15% NaCl）或正常钠（NS；1.27% NaCl）饮食，使其在跑步机上进行AET，每周5次，每天60分钟，速度为15米/分钟，持续90天，或保持 sedentary状态。在AET方案结束时评估血压（BP）、血浆总胆固醇（TC）和甘油三酯（TG）浓度、脂蛋白谱和胰岛素敏感性。测定头臂干中的脂质浸润、血管紧张素II 1型受体（AT1）、晚期糖基化终产物受体（RAGE）、羧甲基赖氨酸（CML）和4-羟基壬烯醛（4-HNE）含量以及基因表达。各组之间的BP和TC以及基因表达相似。与NS饮食相比，LS饮食增加了血管脂质浸润、CML、RAGE、4-HNE、血浆TG、低密度脂蛋白胆固醇和极低密度脂蛋白TG。相反，LS饮食降低了血管AT1受体、胰岛素敏感性、高密度脂蛋白胆固醇和高密度脂蛋白TG。AET预防了动脉脂质浸润；CML、RAGE和4-HNE含量的增加；并降低了AT1水平，改善了LS诱导的外周IR。当前研究表明，AET通过改善头臂干中膜的外周IR、脂质浸润、CML、RAGE、4-HNE和AT1受体，抵消了慢性LS饮食在易发生动脉粥样硬化模型中的有害影响。这些事件独立于血浆脂质谱的改善而发生，血浆脂质谱受到严重饮食钠限制的负面影响。
