Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Sci Rep. 2022 Jan 10;12(1):484. doi: 10.1038/s41598-021-03670-5.
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.
用烟酰胺 N-甲基转移酶抑制剂（NNMTi；5-氨基-1-甲基喹啉）联合低脂饮食（LD）治疗可显著促进饮食诱导肥胖（DIO）小鼠的全身肥胖和体重减轻，迅速使这些指标恢复到与年龄匹配的瘦动物一致，而 LD 转换本身无法在相同的时间框架内使这些指标恢复到与年龄匹配的对照组一致。由于小鼠微生物组谱通常与体重和脂肪组成高度相关，因此本研究旨在测试用 NNMTi 和 LD 治疗的 DIO 小鼠的盲肠微生物组是否与年龄匹配的瘦对应物相似，并且与维持高脂肪西方饮食（WD）的 DIO 小鼠或单独进行 LD 转换的微生物组不同。瘦和肥胖对照组之间的微生物组差异最小，这表明饮食组成和肥胖对其有一定影响。然而，从促进肥胖的 WD 转换为 LD 的 DIO 小鼠（无论治疗状态如何）与肥胖和瘦对照组相比显示出几个属和门的差异。虽然各组之间的 alpha 多样性测量值没有显著差异，但 beta 多样性主坐标分析表明，来自同一治疗组的小鼠最相似。通过动物对扩增子序列变异的 K-means 聚类分析表明，切换到 LD 的 NNMTi 治疗的 DIO 小鼠具有独特的微生物组模式，与载体对照相比，Erysipelatoclostridium 的相对丰度降低，Lactobacillus 的相对丰度增加；这些属与体重和代谢调节有关。此外，与对照组相比，载体处理和 NNMTi 处理的 LD 切换组中相对丰度增加的 Parasutterella 与几种脂肪组织代谢物的丰度显著相关。总之，这些结果为未来的研究提供了新的基础。
