Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cardiomyocyte Heat Production Measured In Vitro with Temperature Probes and by Means of Differential Isothermal Calorimetry Indicates a Role of the ABA/LANCL1-2 Hormone/Receptors System in Thermogenesis

Version 1 : Received: 18 February 2024 / Approved: 20 February 2024 / Online: 20 February 2024 (11:27:28 CET)

How to cite: Zocchi, G.; Fontanelli, F.; Spinelli, S.; Sturla, L.; Passalacqua, M.; Urra, J.C.G.; Delsante, S.; Zocchi, E. Cardiomyocyte Heat Production Measured In Vitro with Temperature Probes and by Means of Differential Isothermal Calorimetry Indicates a Role of the ABA/LANCL1-2 Hormone/Receptors System in Thermogenesis. Preprints 2024, 2024021087. https://doi.org/10.20944/preprints202402.1087.v1 Zocchi, G.; Fontanelli, F.; Spinelli, S.; Sturla, L.; Passalacqua, M.; Urra, J.C.G.; Delsante, S.; Zocchi, E. Cardiomyocyte Heat Production Measured In Vitro with Temperature Probes and by Means of Differential Isothermal Calorimetry Indicates a Role of the ABA/LANCL1-2 Hormone/Receptors System in Thermogenesis. Preprints 2024, 2024021087. https://doi.org/10.20944/preprints202402.1087.v1

Abstract

Abscisic acid (ABA) is a conserved “stress hormone” in unicellular organisms, plants and animals. In mammals, ABA and its receptors LANCL1 and LANCL2 stimulate insulin-independent cell glucose uptake and oxidative metabolism: overexpression of LANCL1/2 increases, and their si-lencing conversely reduces, mitochondrial number, respiration and proton gradient dissipation in muscle cells and in brown adipocytes. We hypothesized that the ABA/LANCL hor-mone/receptors system could be involved in thermogenesis. Heat production by LANCL1/2-overexpressing vs. double-silenced cells was compared in rat H9c2 cardiomyocytes with two different methods: differential temperature measurements using sensitive thermistor probes, and differential isothermal calorimetry. Results indicate that overexpressing cells generate an approx. double amount of thermal power compared with double-silenced cells, and that addition of ABA further doubles heat production in overexpressing cells. With the temperature probes, we find a time-scale of approx. 4 min for thermogenesis to “turn on” after nutrient addition. These results identify the ABA/LANCL hormone receptors system as a hitherto unknown regu-lator of cell thermogenesis. Pharmacologic means of increasing metabolic energy dissipation are considered a promising strategy to reduce oxidative stress and lipid accumulation at a cellular and organismic level: from this study, LANCL1-2 proteins emerge as targetable controllers of ther-mogenesis through their natural ligand ABA.

Keywords

DSC; thermistor probes; H9c2 cardiomyocytes; heat production; mitochondrial uncoupling; LANCL1; LANCL2; ABA

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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