脂蛋白脂肪酶作为肥胖/糖尿病相关心血管疾病的靶点

Rui Shang, Brian Rodrigues
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摘要

在世界范围内,肥胖症和糖尿病的发病率不断上升,心脏病是导致肥胖症和糖尿病患者死亡的主要原因。传统上,肥胖症和糖尿病的治疗主要侧重于减轻体重和控制高血糖。遗憾的是,尽管做出了这些努力,但不良的用药管理使这些患者容易发生心力衰竭。心力衰竭发生的一个诱因是心脏组织如何利用不同的燃料来源获取能量。在这方面,心脏从使用各种底物转变为主要使用脂肪酸(FA)。这种将脂肪酸作为唯一能量来源的转变在疾病初期是有帮助的。然而,随着糖尿病病情的发展,这种转变会产生严重的后果。这是因为过度使用脂肪酸会产生有毒的副产品,从而削弱心脏功能(心脏病)。脂蛋白脂肪酶(LPL)负责调节向心脏输送足量脂肪酸,其在糖尿病期间的功能尚未完全揭示。在这篇综述中,将讨论脂蛋白脂酶在糖尿病控制条件下和糖尿病发生后调节心脏利用燃料的机制,试图找出治疗干预的新靶点。目前,直接针对糖尿病性心脏病的治疗方案还很少,因此对 LPL 的研究可能有助于开发专门针对心脏燃料利用和巨噬细胞中脂质积累的药物,以帮助延缓、预防或治疗心力衰竭,并对糖尿病期间的这一病症进行长期管理。
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Lipoprotein lipase as a target for obesity/diabetes related cardiovascular disease
Worldwide, the prevalence of obesity and diabetes have increased, with heart disease being their leading cause of death. Traditionally, the management of obesity and diabetes has focused mainly on weight reduction and controlling high blood glucose. Unfortunately, despite these efforts, poor medication management predisposes these patients to heart failure. One instigator for the development of heart failure is how cardiac tissue utilizes different sources of fuel for energy. In this regard, the heart switches from using various substrates, to predominantly using fatty acids (FA). This transformation to using FA as an exclusive source of energy is helpful in the initial stages of the disease. However, over the progression of diabetes this has grave end results. This is because toxic by-products are produced by overuse of FA, which weaken heart function (heart disease). Lipoprotein lipase (LPL) is responsible for regulating FA delivery to the heart, and its function during diabetes has not been completely revealed. In this review, the mechanisms by which LPL regulates fuel utilization by the heart in control conditions and following diabetes will be discussed in an attempt to identify new targets for therapeutic intervention. Currently, as treatment options to directly target diabetic heart disease are scarce, research on LPL may assist in drug development that exclusively targets fuel utilization by the heart and lipid accumulation in macrophages to help delay, prevent, or treat cardiac failure, and provide long-term management of this condition during diabetes.
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