Department of Food Science, Yingdong College of Bioengineering, Shaoguan University, 512005 Shaoguan, China.
Food Chem Toxicol. 2012 Sep;50(9):3040-7. doi: 10.1016/j.fct.2012.06.015. Epub 2012 Jun 18.
Elevated concentrations of circulating free fatty acids (FFAs) have been demonstrated to potentially link obesity, insulin resistance and type 2 diabetes. Inhibition of lipolysis reduces FFAs availability and improves insulin sensitivity. Anthocyanins from different plant foods were shown to improve hyperlipidemia and insulin resistance in vivo. In this study, cyanidin-3-O-β-glucoside (C3G), a typical anthocyanin was selected to examine its in vitro effects on high-glucose-induced lipolysis in cultured 3T3-L1 adipocytes. Incubation with C3G efficiently inhibited FFAs and glycerol release from the adipocytes during hyperglycemia in a dose- and time-dependent manner. C3G treatment also increased the activity of AMP-activated protein kinase, decreased the activity of glutamine:fructose 6-phosphate aminotransferase, reduced cellular UDP-N-acetylglucosamine production, thereby suppressing the hexosamine biosynthetic pathway. In addition, C3G attenuated high-glucose-promoted O-glycosylation of transcription factor FoxO1, resulting in decreased expression of adipose triglyceride lipase (ATGL). Our findings reveal a novel mechanism by which anthocyanin regulates FoxO1-mediated transcription of ATGL and thus inhibits adipocyte lipolysis, suggesting its potential therapeutic application in diabetes-associated hyperlipidemia.
循环游离脂肪酸（FFAs）浓度升高已被证明可能与肥胖、胰岛素抵抗和 2 型糖尿病有关。脂肪分解的抑制减少了 FFAs 的可用性并提高了胰岛素敏感性。来自不同植物性食物的花青素已被证明可改善体内的高脂血症和胰岛素抵抗。在这项研究中，选择了典型的花青素矢车菊素-3-O-β-葡萄糖苷（C3G），以检查其在体外对高葡萄糖诱导的培养 3T3-L1 脂肪细胞脂肪分解的影响。C3G 孵育可有效抑制高糖诱导的脂肪细胞中 FFAs 和甘油的释放，呈剂量和时间依赖性。C3G 处理还增加了 AMP 激活蛋白激酶的活性，降低了谷氨酰胺：果糖 6-磷酸氨基转移酶的活性，减少了细胞内 UDP-N-乙酰葡萄糖胺的产生，从而抑制了己糖胺生物合成途径。此外，C3G 减弱了高葡萄糖促进的转录因子 FoxO1 的 O-糖基化，导致脂肪甘油三酯脂肪酶（ATGL）的表达减少。我们的研究结果揭示了花青素调节 FoxO1 介导的 ATGL 转录的新机制，从而抑制脂肪细胞脂肪分解，提示其在糖尿病相关高脂血症中的潜在治疗应用。
