Hartnett Sigurd, Gao Hongbo, Schnack Sabrina, Li Yifan
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota.
Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota
Physiol Rep. 2015 Nov;3(11). doi: 10.14814/phy2.12609.
Suppressed parasympathetic function is commonly present in cardiovascular diseases, aging, obesity, and various other health conditions. Impaired parasympathetic action is known as a detrimental factor and contributes to the adverse outcomes in these conditions. However, the underlying mechanisms remain to be fully addressed. In this study, using high-fat diet (HFD)-induced obese mice as a model, the potential peripheral mechanisms underlying the impaired parasympathetic vagal control of the heart was examined. The HFD induced obesity and metabolic disorder in mice. These obese mice exhibited an attenuated response in heart rate to vagal stimulation, indicating impairment of peripheral parasympathetic activity in the heart. In cholinergic function-related proteins in the atria, protein levels of choline transporter and vesicular acetylcholine transporter were not decreased but increased, and type 2 muscarinic receptors showed a trend toward a reduction in HFD mice atria as compared with regular diet (RD) mice controls. While the protein level of acetylcholinesterase was not different, butyrylcholinesterase (BChE) protein level showed a twofold increase in HFD mice atria as compared with RD mice. Functionally, inhibition of BChE activity partially and significantly improved the attenuated response in heart rate to vagal stimulation in HFD mice. Collectively, these data suggest that increased BChE activity in the atria may contribute to the decreased parasympathetic function in HFD-induced obese mice.
副交感神经功能受抑制常见于心血管疾病、衰老、肥胖及其他各种健康状况中。副交感神经作用受损是一个有害因素，会导致这些情况下出现不良后果。然而，其潜在机制仍有待充分阐明。在本研究中，以高脂饮食（HFD）诱导的肥胖小鼠为模型，研究了心脏副交感神经迷走控制受损的潜在外周机制。高脂饮食诱导了小鼠肥胖和代谢紊乱。这些肥胖小鼠对迷走神经刺激的心率反应减弱，表明心脏外周副交感神经活动受损。在心房与胆碱能功能相关的蛋白质中，胆碱转运体和囊泡乙酰胆碱转运体的蛋白质水平未降低反而升高，与正常饮食（RD）小鼠对照组相比，HFD小鼠心房中的M2型毒蕈碱受体呈减少趋势。虽然乙酰胆碱酯酶的蛋白质水平没有差异，但与RD小鼠相比，HFD小鼠心房中的丁酰胆碱酯酶（BChE）蛋白质水平增加了两倍。在功能上，抑制BChE活性可部分且显著改善HFD小鼠对迷走神经刺激的心率减弱反应。总体而言，这些数据表明，心房中BChE活性增加可能导致HFD诱导的肥胖小鼠副交感神经功能下降。
