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Immunohistochemical staining confirmed a marked reduction in PDHA1 expression in the shPDHA1 group, with partial restoration upon Enz treatment (Fig

Importantly, the effects mediated by SANA occur through an increase in creatine-related energy expenditure, reminiscent of creatine-dependent thermogenesis, or futile creatine cycle 30,31 , a heat-production pathway that can maintain body temperature in the complete absence of UCP1 expression 32

These findings were verified using clinical samples and animal models

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