Department of Pharmacology, School of Basic Medical Sciences, Xian Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, People's Republic of China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Medical Collage, Xian Jiaotong University, Xi'an 710061, Shaanxi, People's Republic of China.
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1037-1050. doi: 10.1016/j.bbadis.2018.01.006. Epub 2018 Jan 6.
Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue.
肥胖是心血管疾病发展的主要原因之一，与自主神经失衡有关，其特征是交感神经活性亢进和迷走神经活性降低。迷走神经激活在体重减轻和改善心脏功能方面发挥着重要作用。吡啶斯的明是一种可逆的乙酰胆碱酯酶抑制剂，但它是否能改善高脂肪饮食喂养大鼠的心脏脂质堆积和心脏重构尚未确定。本研究探讨了吡啶斯的明对高脂肪饮食诱导的心脏功能障碍的影响，并探讨了其潜在机制。大鼠分别给予正常饮食或高脂肪饮食，并给予吡啶斯的明治疗。使用 BL-420S 系统评估迷走神经放电，使用超声心动图评估心脏功能。通过组织学方法评估脂质沉积和心脏重构。通过 qPCR 评估脂质利用率。高脂肪饮食导致迷走神经放电和脂质利用率显著降低，脂质堆积、心脏重构和心脏功能明显增加。吡啶斯的明改善了高脂肪饮食喂养大鼠的迷走神经活动和脂质代谢紊乱以及心脏重构，并改善了心脏功能。还观察到吡啶斯的明治疗大鼠白色脂肪组织的褐色化增加，并与 UCP-1 和 CIDEA 的表达相关。此外，吡啶斯的明通过激活 SIRT-1/AMPK/PGC-1α 通路促进棕色脂肪组织的激活。综上所述，高脂肪饮食导致心脏脂质堆积、心脏重构和迷走神经放电显著减少。吡啶斯的明改善了心肌病，这一作用与减少心脏脂质堆积有关，并促进了白色脂肪组织的褐色化，同时激活了棕色脂肪组织。
