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

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机构： [1]College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Tsinghua East Road, Hai Dian District, Beijing, 100083 People's Republic of China. [2]Research Center for Probiotics, China Agricultural University, Sanhe, 065200 China. [3]Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730 China. [4]Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China. [5]Food Laboratory of Zhongyuan, Luohe, 462300 Henan China.

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关键词： Engineered L lactis Amuc_1631 GLP-1 Thermogenesis Anti-obesity

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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.The online version contains supplementary material available at 10.1007/s13205-025-04465-5.© King Abdulaziz City for Science and Technology 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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出版当年[2025]版：

大类 | 4 区生物学

小类 | 4 区生物工程与应用微生物

最新[2025]版：

大类 | 4 区生物学

小类 | 4 区生物工程与应用微生物

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第一作者机构： [1]College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Tsinghua East Road, Hai Dian District, Beijing, 100083 People's Republic of China.

通讯作者：

通讯机构： [1]College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Tsinghua East Road, Hai Dian District, Beijing, 100083 People's Republic of China. [5]Food Laboratory of Zhongyuan, Luohe, 462300 Henan China.

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