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Specific amino acid supplementation rescues the heart from lipid overload-induced insulin resistance and contractile dysfunction by targeting the endosomal mTOR–v-ATPase axis by Wang, Shujin (author);Schianchi, Francesco (author);Neumann, Dietbert (author);Wong, Li-Yen (author);Sun, Aomin (author);van Nieuwenhoven, Frans A. (author);Zeegers, Maurice P. (author);Strzelecka, Agnieszka (author);Col, Umare (author);Glatz, Jan F.C. (author);Nabben, Miranda (author);Luiken, Joost J.F.P. (author) is a Medicine article available to read on EtoBox.

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## Objective The diabetic heart is characterized by extensive lipid accumulation which often leads to cardiac contractile dysfunction. The underlying mechanism involves a pivotal role for vacuolar-type H^+^-ATPase (v-ATPase, functioning as endosomal/lysosomal proton pump). Specifically, lipid oversupply to the heart causes disassembly of v-ATPase and endosomal deacidification. Endosomes are storage compartments for lipid transporter CD36. However, upon endosomal deacidification, CD36 is expelled to translocate to the sarcolemma, thereby inducing myocardial lipid accumulation, insulin resistance, and contractile dysfunction. Hence, the v-ATPase assembly may be a suitable target for ameliorating diabetic cardiomyopathy. Another function of v-ATPase involves the binding of anabolic master-regulator mTORC1 to endosomes, a prerequisite for the activation of mTORC1 by amino acids (AAs). We examined whether the relationship between v-ATPase and mTORC1 also operates reciprocally; specifically, whether AA induces v-ATPase reassembly in a mTORC1-dependent manner to prevent excess lipids from entering and damaging the heart. ## Methods Lipid overexposed rodent/human cardiomyocytes and high-fa

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Author

Wang, Shujin (author);Schianchi, Francesco (author);Neumann, Dietbert (author);Wong, Li-Yen (author);Sun, Aomin (author);van Nieuwenhoven, Frans A. (author);Zeegers, Maurice P. (author);Strzelecka, Agnieszka (author);Col, Umare (author);Glatz, Jan F.C. (author);Nabben, Miranda (author);Luiken, Joost J.F.P. (author)

Publisher

Elsevier BV

Published

2021

Language

EN

Field

Medicine (Health Sciences)