Ghrelin is a gut
hormone that stimulates food intake. In physiological conditions,
ghrelin plasma levels rise with fasting and decrease after meals. Obese individuals have low fasting
ghrelin levels that rise after food restriction, which is pointed out as a reason for the difficulty in maintaining
weight loss. Some
bariatric surgery procedures prevent rise in
ghrelin levels with
weight loss and this has been hypothesised to contribute to the long-term success of the treatment. The main goal of this study was to develop a safe and effective anti-
ghrelin vaccine for
obesity, through the chemical conjugation of
ghrelin with a virus like particle, namely NS1
protein tubules from the Bluetongue Virus (BTV) using a hetero-bifunctional cross linker. Male adult C57BL/6 mice, with a normal weight and with diet-induced
obesity (DIO), were randomized into six weight matched groups (n=6/group) and each group of mice received three intra-peritoneal
injections with two weeks intervals, containing either 75 μg of
ghrelin- NS1
immunoconjugate, 75 μg of NS1 or PBS. Our data show that immunized animals present increasing titres of anti-
ghrelin antibodies, while their cumulative food intake significantly decreased and energy expenditure was significantly enhanced, although there were no significative changes in
body weight.Vaccinated DIO mice also displayed significant decrease of NPY gene expression in the basal hypothalamus reflecting a decrease in central orexigenic signals. This study suggests that this anti-
ghrelin vaccine has a positive impact on energy homeostasis and may be an additional therapeutical tool to be used with diet and exercise for
obesity treatment.