Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
J Pharm Pharm Sci. 2024 Jul 16;27:13199. doi: 10.3389/jpps.2024.13199. eCollection 2024.
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.
全球范围内,肥胖症和糖尿病的患病率不断增加,心脏病是它们的主要致死原因。传统上,肥胖症和糖尿病的管理主要集中在减轻体重和控制高血糖上。不幸的是,尽管做出了这些努力,由于药物管理不善,这些患者仍容易患上心力衰竭。导致心力衰竭发展的一个因素是心脏组织如何利用不同的燃料来源来获取能量。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 FA 作为唯一能量来源的转变在疾病的早期阶段是有帮助的。然而,随着糖尿病的发展,这种情况会产生严重的后果。这是因为 FA 的过度使用会产生有毒的副产物,从而削弱心脏功能(心脏病)。脂蛋白脂肪酶(LPL)负责调节 FA 向心脏的输送,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 LPL 在对照条件和糖尿病下调节心脏燃料利用的机制,试图确定新的治疗干预靶点。目前,由于直接针对糖尿病性心脏病的治疗选择稀缺,对 LPL 的研究可能有助于药物开发,专门针对心脏的燃料利用和巨噬细胞中的脂质积累,以帮助延缓、预防或治疗心力衰竭,并在糖尿病期间对这种情况进行长期管理。