Guo Chengcheng, Zhang Xiaoyuan, Yu Yingxiang, Wu Yifan, Xie Lan, Chang Cuiqing
Department of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.
Institute of Sports Medicine, Peking University, Beijing, China.
Front Nutr. 2022 Oct 14;9:1007679. doi: 10.3389/fnut.2022.1007679. eCollection 2022.
Prediabetes is considered an important reversible checkpoint in T2DM development, which can be delayed and prevented by early interventions. (LJF), an edible-medicinal herb, is rich in chlorogenic acid (CGA, 5-O-caffeoylquinic acid) and exerts anti-diabetes effects, but its role in prediabetes remains unclear. The purpose of this study was to explore the effects of LJF extract and CGA on rat with prediabetes. Sprague-Dawley rats were given high-fat diet (HFD) to induce prediabetes, and glycolipid metabolism parameters and molecular mechanisms were evaluated. LJF (the LJF extract treatment group) and CGA (the pure CGA treatment group) significantly attenuated HFD-induced prediabetes with impaired glucose tolerance and dyslipidemia, but their mechanisms of action are not exactly the same. Specifically, LJF prioritizes increasing protective lipid species [such as increasing blood polyunsaturated fatty acids (PUFA)-containing diacylglycerol (DAG) species, high-density lipoprotein-cholesterol (HDL-C)], whereas CGA prioritizes reducing detrimental lipid species [such as saturated fatty acid-containing DAG species, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC)]. In addition, CGA significantly increased the content of blood very-long-chain fatty-acid (VLCFA)-containing ceramides species. This could be explained mechanically by a distinction between LJF and CGA's effects on C1q/TNF-related proteins (CTRPs) which activate adiponectin receptors, triggering several downstream reactions. Because both LJF and CGA upregulated liver expression of adiponectin receptors (AdipoR1 and AdipoR2) and enhanced the activity of downstream AMPK. LJF also increased serum levels of CTRP3 and CTRP9, especially CTRP9, whereas CGA had higher serum CTRP3 and upregulated liver PPARa expression. Additionally, ELOVL6 expression in the liver was greater in CGA than LJF. This study demonstrates that LJF and CGA exert hypoglycemic and lipid modulation capacity to prevent prediabetes may through the CTRPs-AdipoRs-AMPK/PPARα axes and promoting ELOVL6 protein expression.
糖尿病前期被认为是2型糖尿病发展过程中一个重要的可逆转节点，早期干预可以延缓和预防其发生。连钱草（LJF）是一种药食同源的草药，富含绿原酸（CGA，5-O-咖啡酰奎尼酸），具有抗糖尿病作用，但其在糖尿病前期中的作用尚不清楚。本研究旨在探讨连钱草提取物和绿原酸对糖尿病前期大鼠的影响。给予Sprague-Dawley大鼠高脂饮食（HFD）以诱导糖尿病前期，评估糖脂代谢参数和分子机制。连钱草（连钱草提取物治疗组）和绿原酸（纯绿原酸治疗组）显著减轻了HFD诱导的糖尿病前期，改善了葡萄糖耐量受损和血脂异常，但其作用机制并不完全相同。具体而言，连钱草优先增加保护性脂质种类（如增加血液中含多不饱和脂肪酸（PUFA）的二酰甘油（DAG）种类、高密度脂蛋白胆固醇（HDL-C）），而绿原酸优先减少有害脂质种类（如含饱和脂肪酸的DAG种类、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC））。此外，绿原酸显著增加了血液中含极长链脂肪酸（VLCFA）的神经酰胺种类的含量。这可以从连钱草和绿原酸对激活脂联素受体的C1q/TNF相关蛋白（CTRPs）的不同作用机制来解释，CTRPs会引发几个下游反应。因为连钱草和绿原酸都上调了肝脏脂联素受体（AdipoR1和AdipoR2）的表达，并增强了下游AMPK的活性。连钱草还增加了血清CTRP3和CTRP9水平，尤其是CTRP9，而绿原酸的血清CTRP3水平更高，并上调了肝脏PPARα的表达。此外，绿原酸组肝脏中ELOVL6的表达高于连钱草组。本研究表明，连钱草和绿原酸可能通过CTRPs-AdipoRs-AMPK/PPARα轴并促进ELOVL6蛋白表达发挥降血糖和调节血脂的能力，从而预防糖尿病前期。
