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Sodium-potassium Adenosine Triphosphatase α2 Subunit (ATP1A2) Negatively Regulates UCP1-dependent and UCP1-independent Thermogenesis in 3T3-L1 Adipocytes

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Abstract

Increasing the number of brite cells (browning) in white adipocytes has attracted considerable attention to combat obesity because brite cells also help elevate energy expenditure. Sodium-potassium adenosine triphosphatase α2 subunit (ATP1A2) has been studied extensively in migraine and cancers. On the other hand, the role of ATP1A2 in adipocytes biology with a focus on fat browning needs to be elucidated. In this study, suppression of ATP1A2 induced browning in white adipocytes. The siRNA-mediated knockdown was used to identify the functional roles of the ATP1A2 gene in white adipocytes browning and the lipid metabolism. A deficiency of ATP1A2 promoted the expression of brown adipocyte-specific proteins and genes, suppressed adipogenesis and lipogenesis, and enhanced lipolysis and fat oxidation, as well as mitochondrial biogenesis. Moreover, silencing of ATP1A2 enhanced the expression of marker proteins for UCPl-dependent (β3-AR, PKA, p38, ATF2, and ERK) and UCP1-independent (α1-AR, SERCA, and RyR) thermogenesis. A mechanistic study showed that a deficiency of ATP1A2 induces browning in white adipocytes by activating the β3-AR/ERK signaling pathways as well as α1-AR/SERCA-based thermogenesis through an ATP-consuming process. In conclusion, ATP1A2 is a previously unrecognized player in thermogenesis in white adipocytes, and downregulating ATP1A2 and activating both UCP1-dependent and UCP1-independent thermogenesis in adipocytes could be a novel pharmacotherapeutic approach to treat obesity.

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Acknowledgements

This research was supported by Daegu University Research Grant, 2023.

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  1. Department of Biotechnology, Daegu University, Gyeongsan, 38453, Korea

    Subramani Manigandan & Jong Won Yun

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  1. Subramani Manigandan
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Manigandan, S., Yun, J.W. Sodium-potassium Adenosine Triphosphatase α2 Subunit (ATP1A2) Negatively Regulates UCP1-dependent and UCP1-independent Thermogenesis in 3T3-L1 Adipocytes. Biotechnol Bioproc E 28, 644–657 (2023). https://doi.org/10.1007/s12257-023-0095-3

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