vements in a wide range of comorbid conditions. Currently approved anti-obesity drugs show only limited efficacy, generally facilitating no more than a 5 10% reduction of body weight and are often associated with unpleasant side-effect profiles. To date the only treatment leading to substantial, sustained body weight loss is bariatric surgery. However, this intervention is associated with between 1.5% and 4.5% mortality during the first three month following surgery. Hence there is a major medical need for the development of new anti-obesity drugs. In the past decade our knowledge of gut hormones and their central role in the control of food intake and energy balance has substantially improved. This increased understanding has led to the identification of new potential targets for pharmaceutical intervention. Vaccination against Obesity like particles are able to efficiently induce self-specific antibody responses in mice and humans. In this study, we show that vaccination against GIP prevents excessive body weight gain in rodents fed a high fat diet and induces increased weight loss in obese mice. Hence, active vaccination may represent an attractive and convenient new therapy for the treatment of obesity. Results Vaccination against GIP results in high levels of GIPspecific antibodies the serum we tested whether specific antibodies would prevent the interaction of GIP with its receptor. Hence, CHOK1 cells expressing the human GIP receptor were generated and used for 16722652 in vitro receptor binding studies. Increasing amounts of purified IgGs from Qb-GIP or Qb immunised mice were incubated with a fixed amount of I125-GIP and added to receptor expressing cells. After overnight incubation at 4uC receptor bound GIP was determined. As shown in Vaccination against GIP protects against diet-induced obesity Having established that Qb-GIP induces a strong antibody response which can efficiently sequester GIP we wanted to investigate whether vaccination against GIP could reduce body weight gain in rodents. Adult, female mice were immunized with Qb-GIP or control Qb VLPs and placed on a high fat diet. As 25137254 shown in Vaccination against GIP increases energy expenditure To further elucidate why animals vaccinated against GIP gained less body weight, food intake, physical activity and energy expenditure were measured after 4 months on a high fat diet. Qb-GIP-vaccinated mice showed significantly higher energy expenditure compared to control mice in both the dark and the light phase. This can best be explained by an increase in basal metabolism, since resting metabolic rate was significantly higher in Qb-GIP-vaccinated animals and no significant increase in physical activity was observed. Moreover, Qb-GIP-vaccinated animals displayed a lower respiratory quotient throughout the experimental period, indicative Vaccination against Obesity 3 Vaccination against Obesity was incubated with increasing LY-2835219 site concentrations of GIP, GLP-1 or oxyntomodulin. The amount of free antibody was quantified by ELISA. Recognition of the N-terminus of full length GIP. A serum pool from Qb-GIP-immunized mice was preincubated either with GIP115 or 
GIP315 and free antibodies quantified by ELISA. Sequestration of GIP in vivo. Qb-GIP immunized mice or naive mice were challenged i.v. with 1 ng of I125-GIP. 30 minutes later the amount of antibody-bound GIP was determined. The percentage of antibody bound GIP6SEM is shown. Antibody mediated blocking of GIP binding to its receptor. I125-GIP was
