PDF(Pubmed)
Abstract：
Chronic lipid overconsumption, associated with the Western diet, causes excessive cardiac lipid accumulation, insulin resistance, and contractile dysfunction, altogether termed lipotoxic cardiomyopathy (LCM). Existing treatments for LCM are limited. Traditional Chinese Medicine (TCM) has been shown as beneficial in diabetes and its complications. The following compounds-Resveratrol, Quercetin, Berberine, Baicalein, and Isorhamnetin-derived from TCM and often used to treat type 2 diabetes. However, virtually nothing is known about their effects in the lipid-overexposed heart. Lipid-induced insulin resistance was generated in HL-1 cardiomyocytes and adult rat cardiomyocytes by 24 h exposure to high palmitate. Upon simultaneous treatment with each of the TCM compounds, we measured myocellular lipid accumulation, insulin-stimulated fatty acid and glucose uptake, phosphorylation levels of AKT and ERK1/2, plasma membrane appearance of GLUT4 and CD36, and expression of oxidative stress-/inflammation-related genes and contractility. In lipid-overloaded cardiomyocytes, all the selected TCM compounds prevented lipid accumulation. These compounds also preserved insulin-stimulated CD36 and GLUT4 translocation and insulin-stimulated glucose uptake in an Akt-independent manner. Moreover, all the TCM compounds prevented and restored lipid-induced contractile dysfunction. Finally, some (not all) of the TCM compounds inhibited oxidative stress-related SIRT3 expression, and others reduced inflammatory TNFα expression. Their ability to restore CD36 trafficking makes all these TCM compounds attractive natural supplements for LCM treatment.
摘要：
慢性脂质过度消耗，与西方饮食有关，导致过度的心脏脂质积累，胰岛素抵抗，和收缩功能障碍，称为脂毒性心肌病（LCM）。LCM的现有处理是有限的。中药（TCM）已被证明对糖尿病及其并发症有益。以下化合物-白藜芦醇，槲皮素,小檗碱,黄芩素,和异鼠李素-来源于中医，常用于治疗2型糖尿病。然而,实际上对它们在脂质过度暴露的心脏中的作用一无所知。通过暴露于高棕榈酸酯24小时，在HL-1心肌细胞和成年大鼠心肌细胞中产生了脂质诱导的胰岛素抵抗。在用每种中药化合物同时治疗后，我们测量了肌细胞脂质的积累，胰岛素刺激的脂肪酸和葡萄糖摄取，AKT和ERK1/2的磷酸化水平，GLUT4和CD36的质膜外观以及氧化应激/炎症相关基因的表达和收缩力。在脂质过载的心肌细胞中，所有选定的中药化合物均可防止脂质积聚。这些化合物还以Akt非依赖性方式保留了胰岛素刺激的CD36和GLUT4易位和胰岛素刺激的葡萄糖摄取。此外，所有中药复方均可预防和恢复脂质诱导的收缩功能障碍。最后,一些（不是全部）中药化合物抑制氧化应激相关的SIRT3表达，和其他降低炎性TNFα表达。它们恢复CD36贩运的能力使所有这些中药化合物对LCM治疗具有吸引力的天然补充剂。
