Cardiac lipid metabolism, mitochondrial function, and heart failure

Author:

Da Dalt Lorenzo1ORCID,Cabodevilla Ainara G2ORCID,Goldberg Ira J2,Norata Giuseppe Danilo13ORCID

Affiliation:

1. Department of Pharmacological and Biomolecular Sciences, University of Milan , Via Balzaretti 9, Milan , Italy

2. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, 550 1st Ave., New York, NY, USA

3. Center for the Study of Atherosclerosis, E. Bassini Hospital, Via Massimo Gorki 50, Cinisello Balsamo , Italy

Abstract

Abstract A fine balance between uptake, storage, and the use of high energy fuels, like lipids, is crucial in the homeostasis of different metabolic tissues. Nowhere is this balance more important and more precarious than in the heart. This highly energy-demanding muscle normally oxidizes almost all the available substrates to generate energy, with fatty acids being the preferred source under physiological conditions. In patients with cardiomyopathies and heart failure, changes in the main energetic substrate are observed; these hearts often prefer to utilize glucose rather than oxidizing fatty acids. An imbalance between uptake and oxidation of fatty acid can result in cellular lipid accumulation and cytotoxicity. In this review, we will focus on the sources and uptake pathways used to direct fatty acids to cardiomyocytes. We will then discuss the intracellular machinery used to either store or oxidize these lipids and explain how disruptions in homeostasis can lead to mitochondrial dysfunction and heart failure. Moreover, we will also discuss the role of cholesterol accumulation in cardiomyocytes. Our discussion will attempt to weave in vitro experiments and in vivo data from mice and humans and use several human diseases to illustrate metabolism gone haywire as a cause of or accomplice to cardiac dysfunction.

Funder

Telethon Foundation

Progetti di Rilevante Interesse Nazionale

Ministry of Health

PNRR, Centro Nazionale Di Ricerca 3

PNRR Ecosistemi per L’Innovazione

National Heart Blood and Lung Institute

American Heart Association

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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