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Cell culture studies using adipocytes have shown that NNMT overexpression promotes lipid accumulation and insulin resistance, while NNMT knockdown or inhibition increases NAD+ levels, activates SIRT1, enhances mitochondrial respiration, promotes expression of thermogenic genes including UCP1, and drives white adipocyte browning toward a beige phenotype

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This dual preservation creates a unique metabolic environment where cells can simultaneously maintain high energy production capacity and robust epigenetic regulation a combination that typically requires careful balance between competing metabolic demands