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Reviews in Endocrine and Metabolic Disorders

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Open Access 01-02-2022 | Obesity

ATP-consuming futile cycles as energy dissipating mechanisms to counteract obesity

Authors: Alexandra J. Brownstein, Michaela Veliova, Rebeca Acin-Perez, Marc Liesa, Orian S. Shirihai

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 1/2022

Abstract

Obesity results from an imbalance in energy homeostasis, whereby excessive energy intake exceeds caloric expenditure. Energy can be dissipated out of an organism by producing heat (thermogenesis), explaining the long-standing interest in exploiting thermogenic processes to counteract obesity. Mitochondrial uncoupling is a process that expends energy by oxidizing nutrients to produce heat, instead of ATP synthesis. Energy can also be dissipated through mechanisms that do not involve mitochondrial uncoupling. Such mechanisms include futile cycles described as metabolic reactions that consume ATP to produce a product from a substrate but then converting the product back into the original substrate, releasing the energy as heat. Energy dissipation driven by cellular ATP demand can be regulated by adjusting the speed and number of futile cycles. Energy consuming futile cycles that are reviewed here are lipolysis/fatty acid re-esterification cycle, creatine/phosphocreatine cycle, and the SERCA-mediated calcium import and export cycle. Their reliance on ATP emphasizes that mitochondrial oxidative function coupled to ATP synthesis, and not just uncoupling, can play a role in thermogenic energy dissipation. Here, we review ATP consuming futile cycles, the evidence for their function in humans, and their potential employment as a strategy to dissipate energy and counteract obesity.

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Title: ATP-consuming futile cycles as energy dissipating mechanisms to counteract obesity
Authors: Alexandra J. Brownstein
Michaela Veliova
Rebeca Acin-Perez
Marc Liesa
Orian S. Shirihai
Publication date: 01-02-2022
Publisher: Springer US
Keywords: Obesity
Obesity
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 1/2022
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-021-09690-w

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Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

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