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The original genetic-validation study used antisense oligonucleotide-mediated knockdown of NNMT in adipose tissue of mice on a high-fat diet, with whole-body and adipose-tissue metabolic endpoints measured against scrambled-oligonucleotide controls [2]
SAM and SAH were quantified using a method adapted from Blaise et al

Chronic, uninterrupted activation can lead to pathway desensitization, the biological equivalent of diminishing returns
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