Study summary · research use only
Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this diet-induced obese (DIO) mouse study, researchers examined a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with a low-fat diet (LD) and its association with gut microbiome composition, since prior work linked this combination to weight and adiposity loss. Cecal microbiomes of treated DIO mice were compared to lean controls and to DIO mice on a high-fat Western diet or switched to LD alone. Minimal differences were found between lean and obese controls, but DIO mice switched to LD, regardless of treatment, showed genera and phyla differences versus obese and lean controls. Beta diversity analysis suggested mice from the same treatment group were most similar. NNMTi-treated, LD-switched mice showed decreased Erysipelatoclostridium and increased Lactobacillus relative to vehicle controls, and Parasutterella abundance correlated with adipose tissue metabolite levels.
Abstract
Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites' abundances. Collectively, these results provide a novel foundation for future investigations.
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