Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice.
Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice.
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DOI：
10.1038/s41598-021-85051-6
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发表时间：
2021-03-11
影响因子：
4.6
通讯作者：
Watowich SJ
中科院分区：
文献类型：
--
作者：
Sampson CM;Dimet AL;Neelakantan H;Ogunseye KO;Stevenson HL;Hommel JD;Watowich SJ
肥胖是一个巨大的和日益增长的全球健康问题，几乎没有有效的治疗方法。本研究探讨了烟酰胺N-甲基转移酶抑制剂（NNMTi）治疗结合饮食诱导的肥胖小鼠中的瘦饮食替代的代谢和生理益处。相对于单独的瘦肉型饮食替代，NNMTi治疗与瘦肉型饮食替代组合加速并改善了体重和脂肪减轻，增加了全身瘦体重/体重比，降低了肝脏和附睾白色脂肪组织重量，降低了肝脏肥胖，并改善了肝脏脂肪变性。重要的是，组合的瘦饮食和NNMTi治疗使身体组成和肝脏肥胖参数正常化至在年龄匹配的瘦饮食对照小鼠中观察到的水平。NNMTi处理在脂肪组织中产生了独特的代谢组学特征，主要是生酮氨基酸丰度增加和与能量代谢途径相关的代谢物改变。总而言之，NNMTi治疗对体重、肥胖、肝脏生理学和脂肪组织代谢组的调节强烈支持其作为肥胖和肥胖驱动的合并症的有希望的治疗方法。
Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
DOI：
10.1146/annurev-cellbio-100814-125544
发表时间：
2015
影响因子：
11.3
作者：
Janke R;Dodson AE;Rine J
通讯作者：
Rine J
影响因子：
12.7
作者：
Fildes, Alison;Charlton, Judith;Gulliford, Martin C.
通讯作者：
Gulliford, Martin C.
影响因子：
4.2
作者：
Ito, Makoto;Suzuki, Jun;Kanatani, Akio
通讯作者：
Kanatani, Akio
影响因子：
5
作者：
Chusyd DE;Wang D;Huffman DM;Nagy TR
通讯作者：
Nagy TR