Effects of intranasal administration of a leptin-secreting Lactococcus lactis recombinant on food intake body weight, and immune response of mice
Effects of intranasal administration of a leptin-secreting Lactococcus lactis recombinant on food intake body weight, and immune response of mice
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DOI：
10.1128/aem.00295-07
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Issad, Tarik
中科院分区：
文献类型：
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作者：
Bermudez-Humaran, Luis G.;Nouaille, Sebastien;Issad, Tarik
瘦素是一种脂肪细胞衍生的多效激素，可调节大量生理功能，包括控制体重和免疫系统的调节。在这项工作中，我们表明食品级乳酸菌乳酸菌（LL-LEP）的重组菌株可以产生并有效地分泌人类瘦素。分泌的瘦素是一种完全具有生物活性的激素，这是由于其刺激用OB-RB瘦素受体转染的HEK293细胞中STAT3报告基因基因的能力所证明的。通过与人乳头瘤病毒16 E7蛋白共表达，在体内评估了分泌乳酸乳杆菌的免疫调节活性。在C57BL/6小鼠中，用重组L.乳酸乳杆菌菌株结合瘦素和E7抗原在鼻内免疫，适应性免疫反应明显高于仅生产E7抗原的重组L.乳酸乳杆菌免疫的小鼠中，表现出E7抗原。然后，我们分析了鼻内施用的LL-LEP在肥胖OB/OB小鼠中的影响。我们观察到，这些小鼠的LL-LEP每天给药可显着减少体重增加和食物摄入量。这些结果表明，瘦素可以由乳酸乳乳乳糖浆以活性形式产生和分泌，而产生瘦素的乳酸乳杆菌可以调节体内抗原特异性免疫反应，体重和食物的消耗。
Leptin is an adipocyte-derived pleiotropic hormone that modulates a large number of physiological functions, including control of body weight and regulation of the immune system. In this work, we show that a recombinant strain of the food-grade lactic acid bacterium Lactococcus lactis (LL-lep) can produce and efficiently secrete human leptin. The secreted leptin is a fully biologically active hormone, as demonstrated by its capacity to stimulate a STAT3 reporter gene in HEK293 cells transfected with the Ob-Rb leptin receptor. The immunomodulatory activity of leptin-secreting L. lactis was evaluated in vivo by coexpression with the human papillomavirus type 16 E7 protein. In C57BL/6 mice immunized intranasally with a recombinant L. lactis strain coproducing leptin and E7 antigen, the adaptive immune response was significantly higher than in mice immunized with recombinant L. lactis producing only E7 antigen, demonstrating adjuvanticity of leptin. We then analyzed the effects of intranasally administered LL-lep in obese ob/ob mice. We observed that daily administration of LL-lep to these mice significantly reduced body weight gain and food intake. These results demonstrate that leptin can be produced and secreted in an active form by L. lactis and that leptin-producing L. lactis regulates in vivo antigen-specific immune responses, as well as body weight and food consumption.