Microbial creation of β-Nicotinamide mononucleotide and its regulation of lipid metabolism in the liver of high-fat diet mice

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Function Pub Date : 2024-07-02 DOI:10.1002/cbf.4087

Xutong Tian, Youyan Rong, Juyue Luo, Yaping Zhao, Tiantian Zhou, Yu Zeng, Kai Hong, Liang Jiang, Jianying Yang, Yumeng Li, Xin Wu

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引用次数: 0

Abstract

β-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide adenine dinucleotide (NAD⁺). To determine the safety and biological activity of NMN resources, we constructed a recombinant strain of P. pastoris that heterologously expresses nicotinamide-phosphate ribosyltransferase (NAMPT), and subsequently catalyzed and purified the expressed product to obtain NMN. Consequently, this study established a high-fat diet (HFD) obese model to investigate the lipid-lowering activity of NMN. The findings showed that NMN supplementation directly increased the NAD⁺ levels, and reduced HFD-induced liver injury and lipid deposition. NMN treatment significantly decreased total cholesterol (TC) and triglyceride (TG) in serum and liver, as well as alanine aminotransferase (ALT) and insulin levels in serum (p < .05 or p < .01). In conclusion, this study combined synthetic biology with nutritional evaluation to confirm that P. pastoris-generated NMN modulated lipid metabolism in HFD mice, offering a theoretical framework and evidence for the application of microbially created NMN.

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微生物产生的β-烟酰胺单核苷酸及其对高脂饮食小鼠肝脏脂质代谢的调节作用

β-烟酰胺单核苷酸（NMN）是一种具有生物活性的核苷酸，它通过快速增加烟酰胺腺嘌呤二核苷酸（NAD+）来调节机体的生理代谢。为了确定 NMN 资源的安全性和生物活性，我们构建了一株异源表达烟酰胺-磷酸核糖基转移酶（NAMPT）的 P. pastoris 重组菌株，随后对表达产物进行催化和纯化以获得 NMN。因此，本研究建立了一个高脂饮食（HFD）肥胖模型来研究 NMN 的降脂活性。研究结果表明，补充 NMN 可直接提高 NAD+ 水平，减少高脂饮食引起的肝损伤和脂质沉积。NMN 治疗可明显降低血清和肝脏中的总胆固醇（TC）和甘油三酯（TG），以及血清中的丙氨酸氨基转移酶（ALT）和胰岛素水平（p

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来源期刊

Cell Biochemistry and Function 生物-生化与分子生物学

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Cell Biochemistry and Function publishes original research articles and reviews on the mechanisms whereby molecular and biochemical processes control cellular activity with a particular emphasis on the integration of molecular and cell biology, biochemistry and physiology in the regulation of tissue function in health and disease. The primary remit of the journal is on mammalian biology both in vivo and in vitro but studies of cells in situ are especially encouraged. Observational and pathological studies will be considered providing they include a rational discussion of the possible molecular and biochemical mechanisms behind them and the immediate impact of these observations to our understanding of mammalian biology.