Engineered Lactococcus lactis secreting a glucagon-like peptide-1-inducing protein P9 for amelioration of obesity in mice.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-09-01 Epub Date: 2025-08-15 DOI:10.1007/s13205-025-04465-5

Wenxuan Di, Xiaoyue Bai, Shuangrui Tian, Liang Zhao, Xi Cao, Yanling Hao, Zhengyuan Zhai

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Abstract

This study investigated the anti-obesity potential of Lactococcus lactis engineered to constitutively secrete P9 (Amuc_1631), a protein from Akkermansia muciniphila. Our findings show that the engineered strain L. lactis P11P9 effectively secretes P9 and significantly increases GLP-1 production in NCI-H716 enteroendocrine cells, with a 2.65-fold rise compared to controls. In high-fat diet (HFD)-induced obese mice, oral administration of L. lactis P11P9 resulted in reduced weight gain, decreased food intake, and attenuation of adipocyte hypertrophy. ELISA analysis of serum samples indicated that L. lactis P11P9 treatment elevated circulating GLP-1 levels. RT-qPCR analysis further revealed increased expression of GLP-1 synthesis-related genes (e.g., GCG and PCSK1) in intestinal tissues. In addition, transcription of thermogenesis-associated genes such as UCP1 and PGC-1α was upregulated in adipose tissue. Taken together, this study suggests that engineered L. lactis P11P9 helps reduce obesity by increasing GLP-1 secretion and stimulating thermogenesis, providing a promising strategy for obesity treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04465-5.

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分泌胰高血糖素样肽-1诱导蛋白P9的工程乳酸乳球菌改善小鼠肥胖。

本研究研究了乳酸乳球菌组成性分泌P9 （Amuc_1631）的抗肥胖潜力，这是一种来自嗜粘乳乳球菌的蛋白质。我们的研究结果表明，工程菌株乳酸乳杆菌P11P9能有效分泌P9，并显著增加NCI-H716肠内分泌细胞中GLP-1的产量，比对照组增加2.65倍。在高脂肪饮食（HFD）诱导的肥胖小鼠中，口服乳杆菌P11P9可减少体重增加，减少食物摄入量，并抑制脂肪细胞肥大。ELISA分析血清样品显示乳杆菌P11P9处理可提高循环GLP-1水平。RT-qPCR分析进一步发现肠组织中GLP-1合成相关基因（如GCG、PCSK1）表达增加。此外，产热相关基因如UCP1和PGC-1α的转录在脂肪组织中上调。综上所述，本研究表明，工程乳杆菌P11P9通过增加GLP-1分泌和刺激生热作用来帮助减少肥胖，为肥胖治疗提供了一个有希望的策略。补充资料：在线版本包含补充资料，下载地址：10.1007/s13205-025-04465-5。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.