Endosomal v-ATPase as a Sensor Determining Myocardial Substrate Preference

作者全名："Wang, Shujin; Han, Yinying; Nabben, Miranda; Neumann, Dietbert; Luiken, Joost J. F. P.; Glatz, Jan F. C."

作者地址："[Wang, Shujin; Han, Yinying] Chongqing Med Univ, Inst Life Sci, Chongqing 400032, Peoples R China; [Wang, Shujin; Nabben, Miranda; Luiken, Joost J. F. P.; Glatz, Jan F. C.] Maastricht Univ, Fac Hlth Med & Life Sci, Dept Genet & Cell Biol, NL-6200 MD Maastricht, Netherlands; [Nabben, Miranda; Neumann, Dietbert] CARIM Sch Cardiovasc Dis, NL-6211 LK Maastricht, Netherlands; [Nabben, Miranda; Luiken, Joost J. F. P.; Glatz, Jan F. C.] Maastricht Univ Med Ctr, Dept Clin Genet, NL-6229 HX Maastricht, Netherlands"

通信作者："Glatz, JFC (通讯作者)，Maastricht Univ, Fac Hlth Med & Life Sci, Dept Genet & Cell Biol, NL-6200 MD Maastricht, Netherlands.; Glatz, JFC (通讯作者)，Maastricht Univ Med Ctr, Dept Clin Genet, NL-6229 HX Maastricht, Netherlands."

来源：METABOLITES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000834490200001

JCR分区：Q2

影响因子：4.1

年份：2022

卷号：12

期号：7

开始页：　

结束页：　

文献类型：Review

关键词：heart; vacuolar-type H+-ATPase; endosomal acidification; lipid; glucose; amino acids; CD36; GLUT4

摘要："The heart is a metabolically flexible omnivore that can utilize a variety of substrates for energy provision. To fulfill cardiac energy requirements, the healthy adult heart mainly uses long-chain fatty acids and glucose in a balanced manner, but when exposed to physiological or pathological stimuli, it can switch its substrate preference to alternative substrates such as amino acids (AAs) and ketone bodies. Using the failing heart as an example, upon stress, the fatty acid/glucose substrate balance is upset, resulting in an over-reliance on either fatty acids or glucose. A chronic fuel shift towards a single type of substrate is linked with cardiac dysfunction. Re-balancing myocardial substrate preference is suggested as an effective strategy to rescue the failing heart. In the last decade, we revealed that vacuolar-type H+-ATPase (v-ATPase) functions as a key regulator of myocardial substrate preference and, therefore, as a novel potential treatment approach for the failing heart. Fatty acids, glucose, and AAs selectively influence the assembly state of v-ATPase resulting in modulation of its proton-pumping activity. In this review, we summarize these novel insights on v-ATPase as an integrator of nutritional information. We also describe its exploitation as a therapeutic target with focus on supplementation of AA as a nutraceutical approach to fight lipid-induced insulin resistance and contractile dysfunction of the heart."

基金机构：National Natural Science Foundation of China [8210033375]; Dutch Heart Foundation Dekker grant [2019T041]; ZonMw Off Road grant [04510011910065]

基金资助正文："S.W. is the recipient of a grant from the National Natural Science Foundation of China (nr. 8210033375). M.N. is the recipient of a Dutch Heart Foundation Dekker grant, nr. 2019T041 and a ZonMw Off Road grant, nr. 04510011910065."