关键词: Pichia pastoris heterologous expression high‐fat diet lipid metabolism β‐Nicotinamide mononucleotide

Mesh : Animals Nicotinamide Mononucleotide / metabolism pharmacology Lipid Metabolism / drug effects Diet, High-Fat Mice Liver / metabolism Male Mice, Inbred C57BL Nicotinamide Phosphoribosyltransferase / metabolism

来  源:   DOI:10.1002/cbf.4087

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.
摘要:
β-烟酰胺单核苷酸(NMN)是通过快速增加烟酰胺腺嘌呤二核苷酸(NAD+)来调节机体生理代谢的生物活性核苷酸。为了确定NMN资源的安全性和生物活性,我们构建了异源表达烟酰胺磷酸核糖基转移酶(NAMPT)的巴斯德毕赤酵母重组菌株,随后催化和纯化表达的产物以获得NMN。因此,本研究建立高脂饮食(HFD)肥胖模型,探讨NMN的降脂活性。研究结果表明,补充NMN直接增加了NAD+水平,减少HFD诱导的肝损伤和脂质沉积。NMN医治显著下降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<.05或p<.01)。总之,本研究将合成生物学与营养评价相结合,证实巴斯德毕赤酵母产生的NMN调节HFD小鼠的脂质代谢,为微生物创造的NMN的应用提供了理论框架和证据。
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