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Applied and Environmental Microbiology, August 2007, p. 5300-5307, Vol. 73, No. 16
0099-2240/07/$08.00+0     doi:10.1128/AEM.00295-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effects of Intranasal Administration of a Leptin-Secreting Lactococcus lactis Recombinant on Food Intake, Body Weight, and Immune Response of Mice{triangledown}

Luis G. Bermúdez-Humarán,1 Sébastien Nouaille,2,3 Vladimir Zilberfarb,2,3 Gérard Corthier,1 Alexandra Gruss,4 Philippe Langella,1,{dagger} and Tarik Issad2,3,{dagger}*

Unité d'Ecologie et de Physiologie du Système Digestif, INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France,1 Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France,2 Inserm, U567, Paris, France,3 Unité des Bactéries Lactiques et Pathogènes Opportunistes, INRA, Domaine de Vilvert, 78352 Jouy en Josas cedex, France4

Received 6 February 2007/ Accepted 20 June 2007

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.

* Corresponding author. Mailing address: Institut Cochin, Département de Biologie Cellulaire, 22 Rue Méchain, 75014 Paris, France. Phone: (331)-40-51-64-09. Fax: (331)-40-51-64-30. E-mail: issad{at}cochin.inserm.fr

{triangledown} Published ahead of print on 29 June 2007.

{dagger} Tarik Issad and Philippe Langella share the senior authorship of this work.

Applied and Environmental Microbiology, August 2007, p. 5300-5307, Vol. 73, No. 16
0099-2240/07/$08.00+0     doi:10.1128/AEM.00295-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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