Effects of intranasal administration with Lactococcus lactis secreting leptin on food intake, body weight and immune response in mice

Unité d'Ecologie et de Physiologie du Système Digestif, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France; Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; Inserm, U567, Paris, France; Unité des Bactéries Lactiques et pathogènes Opportunistes, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France

^* To whom correspondence should be addressed. Email: issad{at}cochin.inserm.fr.

	Abstract

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 co-expression with the human papillomavirus type-16 (HPV-16) E7 protein. In C57BL/6 mice immunized intranasally with recombinant L. lactis strain co-producing 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.