Data_Sheet_2_Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge.xlsx

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition.
Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges.
Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group.
Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases.

背景：营养过载诱导的氧化应激与胰岛素抵抗（insulin resistance）的发病机制密切相关，而胰岛素抵抗又与代谢综合征、肥胖、2型糖尿病及糖尿病血管并发症存在关联。迄今，针对肥胖与消瘦个体在摄入宏量营养素组成各异的不同膳食后，其氧化应激通路基因表达的餐后变化特征尚未被阐明。本研究旨在探究膳食组成是否/如何调控肥胖与消瘦个体的氧化应激应答。

方法：本研究为受试者（消瘦胰岛素敏感者，n=9；肥胖胰岛素抵抗者，n=9）提供高碳水化合物（HC）、高脂肪（HF）或高蛋白（HP）混合流质膳食。分别于基线及餐后长达6小时的多个时间点，采集新鲜外周血来源的单核细胞（MNC），检测血浆葡萄糖与胰岛素水平、血脂谱、尿F2-异前列腺素（F2-IsoP）以及氧化应激通路基因的表达水平。比较接受上述膳食负荷试验的胰岛素敏感与抵抗两组间各参数的差异。

结果：与消瘦受试者相比，无论膳食类型如何，肥胖个体在餐后状态下的促氧化基因（如CYBB、CYBA）与抗氧化基因（如TXN RD1）表达均显著上调（组×时间交互P<0.05）。与之相反，消瘦受试者在摄入HC膳食后NCF-4基因（促氧化）的表达更高，而在摄入HC与HF膳食后SOD1基因（抗氧化）的表达更高（组×膳食交互P<0.05）。肥胖组的餐后尿F2-IsoP水平显著升高（P<0.05），而消瘦组未出现该变化。

结论：本研究结果或代表一种适应性氧化应答，以缓解急性营养过剩诱导的氧化应激加剧。此外，结果提示肥胖个体的氧化应激易感性升高。长期营养过剩导致体重与体脂量增加，可能引发失代偿，进而加重胰岛素抵抗及其相关后遗症。本研究的发现可为心血管疾病高风险肥胖人群的膳食推荐提供参考依据。