Role of the ABA-LANCL1/2 hormone/receptors system in thermogenesis of cardiomyocytes and myoblasts

Abscisic acid (ABA) is a phytohormone conserved across kingdoms and also present in mammals, where it interacts with two receptors, LANCL1 and LANCL2 [1, 2]. The ABA-LANCL1/2 system plays a crucial role in regulating energy metabolism by activating the AMPK/PGC-1α/ERRα pathway. This activation enhances glucose uptake, mitochondrial biogenesis, respiration, and uncoupling of oxidative phosphorylation in rodent skeletal myocytes, human brown adipocytes, and rat cardiomyocytes [1-4]. This study aims to investigate the role of the ABA-LANCL1/2 system in the thermogenesis of cardiomyocytes and myoblasts. To this end, LANCL1 and LANCL2 proteins were either overexpressed or silenced in H9c2 rat cardiomyocytes and C2C12 murine myoblasts by lentiviral transduction [3, 4]. Heat production in these cells was directly measured in these cells using high-sensitivity thermistor probes and further validated through Differential Scanning Calorimetry (DSC). Additionally, C2C12 myoblasts with modified LANCL1/2 expression were differentiated into myotubes, and the expression of key myogenic and thermogenic markers was analyzed by qPCR and Western blot. The results demonstrated that both LANCL1/2-overexpressing cardiomyocytes and myoblasts exhibited significantly increased heat production, generating approximately twice as much heat as double-silenced cells. Treatment with ABA further enhanced heat generation, highlighting the hormone’s ability to potentiate LANCL-mediated thermogenic responses [5]. Moreover, ABA-LANCL1/2 system significantly upregulated the expression of proteins associated with myogenic differentiation and thermogenesis in myoblasts. Together with previous findings on LANCL1/2-mediated uncoupling of oxidative phosphorylation in myocytes and brown adipocytes, these results reveal a previously unrecognized role for the ABA-LANCL1/2 system as a key regulator of cellular thermogenesis.