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Given that both diet composition and adiposity can each substantially impact the gut microflora in obese mice 24 , we conducted a secondary endpoint study using animals given the same series of diets to test the hypothesis that NNMTi treatment combined with LD, but not LD alone, shifts the cecal microbiome profile of obese animals to be similar to age-matched LD controls that were never given a high-fat diet

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In vivo animal experiments showed that daily administration of NNMTi for 28 days to dietinduced obese (DIO) mice significantly upregulated the expression of lipolysisrelated genes (such as ATGL and HSL) and downregulated lipogenesisrelated genes (such as FAS and ACC), indicating that NNMTi effectively promotes fat breakdown and inhibits fat synthesis