Table_1_The association between the size of adipocyte-derived extracellular vesicles and fasting serum triglyceride-glucose index as proxy measures of adipose tissue insulin resistance in a rat model of early-stage obesity.pdf

IntroductionObesity is a complex disease that predisposes individuals to cardiometabolic alterations. It leads to adipose tissue (AT) dysfunction, which triggers insulin resistance (IR). This suggests that people with obesity develop local IR first and systemic IR later. AT secretes extracellular vesicles, which may be physiopathologically associated with the development of IR. Our aim was to evaluate the effect of a high-fat diet on different parameters of adiposity in a rat model of early-stage obesity and to determine if these parameters are associated with markers of systemic IR. In addition, we sought to explore the relationship between fasting blood measures of IR (Triglycerides/High Density Lipoprotein-cholesterol [TAG/HDL-c] and Triglycerides-Glucose Index [TyG Index]) with the size of adipocyte-derived extracellular vesicles (adEV).
MethodsWe used a model of diet-induced obesity for ten weeks in Wistar rats exposed to a high-fat diet. Final weight gain was analyzed by Dual X-ray absorptiometry. Visceral obesity was measured as epididymal AT weight. IR was evaluated with fasting TyG Index & TAG/HDL-c, and adEV were isolated from mature adipocytes on ceiling culture.
ResultsIn the high-fat diet group, glucose and triglyceride blood concentrations were higher in comparison to the control group (Log2FC, 0.5 and 1.5 times higher, respectively). The values for TyG Index and adEV size were different between the control animals and the high-fat diet group. Multiple linear regression analyses showed that adEV size can be significantly associated with the TyG Index value, when controlling for epididymal AT weight.
ConclusionOur results show that lipid and glucose metabolism, as well as the size and zeta potential of adEV are already altered in early-stage obesity and that adEV size can be significantly associated with liver and systemic IR, estimated by TyG Index.

引言
肥胖是一种复杂的疾病，可使个体易患心血管代谢异常。该疾病会引发脂肪组织（adipose tissue, AT）功能障碍，进而诱发胰岛素抵抗（insulin resistance, IR）。这表明肥胖人群首先出现局部胰岛素抵抗，随后发展为全身性胰岛素抵抗。脂肪组织可分泌细胞外囊泡，其可能在病理生理层面与胰岛素抵抗的发生发展相关。本研究旨在评估高脂饮食对早期肥胖大鼠模型中不同肥胖相关参数的影响，并明确这些参数是否与全身性胰岛素抵抗的标志物相关。此外，本研究还探讨了空腹血液胰岛素抵抗指标——甘油三酯/高密度脂蛋白胆固醇（Triglycerides/High Density Lipoprotein-cholesterol, TAG/HDL-c）及甘油三酯-葡萄糖指数（Triglycerides-Glucose Index, TyG Index）与脂肪细胞源性细胞外囊泡（adipocyte-derived extracellular vesicles, adEV）粒径之间的关联。

方法
本研究采用高脂饮食喂养10周的饮食诱导肥胖Wistar大鼠模型。采用双能X线吸收法分析最终体重变化。以附睾脂肪组织重量作为内脏肥胖的评估指标。采用空腹TyG指数及TAG/HDL-c比值评估胰岛素抵抗，并通过天花板培养法从成熟脂肪细胞中分离得到adEV。

结果
与对照组相比，高脂饮食组大鼠的血糖及甘油三酯血液浓度更高（对数2倍变化量分别升高0.5倍和1.5倍）。对照组与高脂饮食组大鼠的TyG指数及adEV粒径存在显著差异。多元线性回归分析结果显示，在校正附睾脂肪组织重量后，adEV粒径与TyG指数存在显著关联。

结论
本研究结果表明，早期肥胖阶段已出现脂质与葡萄糖代谢异常，同时adEV的粒径及ζ电位亦发生改变；且经TyG指数评估的肝脏及全身性胰岛素抵抗与adEV粒径存在显著关联。