A futile Na(+) K(+) transport cycle augments energy expenditure in beige adipocytes.

A futile Na+/K+ transport cycle, driven by ATP1A2, is preferentially amplified in mouse and human beige adipocytes and boosts UCP1-independent energy expenditure.

• Why it matters: UCP1-independent dissipation exists in beige fat, but the specific ATP-consuming ion-transport mechanism and its physiological control were unclear.
• What they did: Cold exposure activates a sympathetic–thyroid hormone axis that induces ATP1A2 and Na+ and K+ channels, increasing bidirectional ion flux while preserving ionic balance; acute Na+/K+-ATPase inhibition and Atp1a2 gain- and loss-of-function tests were used in mouse and human beige adipocytes.
• The result: Inhibiting Na+/K+-ATPase lowers energy expenditure, while Atp1a2 overexpression raises it independent of UCP1; adipocyte-specific Atp1a2 deletion reduces thermogenic capacity and worsens diet-induced obesity, and a human ATP1A2 missense variant diminishes ATP1A2-dependent respiration.

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