Abstract
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.
Highlights
Obesity is increasing worldwide [1, 2]
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
Suggest that weight loss attained after bariatric surgery is due to endocrine effects of the surgery, which are able to interfere with appetite pathways by suppressing the rise in ghrelin levels that is usually observed after caloric deprivation [9, 10]
Summary
Obesity is increasing worldwide [1, 2]. Obesity is associated with enhanced prevalence of several co-morbidities such as type 2 diabetes mellitus, metabolic syndrome and cardiovascular diseases [3, 4] and weight loss improves or resolves several co-morbid conditions associated with the disorder [5]. Clinicians have few tools to fight obesity. Bariatric surgery is the only therapy that provides sustainable weight reduction [8]. Suggest that weight loss attained after bariatric surgery is due to endocrine effects of the surgery, which are able to interfere with appetite pathways by suppressing the rise in ghrelin levels that is usually observed after caloric deprivation [9, 10]
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