Different therapeutic approaches to obesity

Resumo

The prevalence of obesity has been increasing exponentially worldwide which led the World Health Organization classified the disease as the pandemic of the XXI century. Although its proven efficiency, the mechanisms by which bariatric surgery achieves weight loss are yet not fully understood. This is the case of the sleeve gastrectomy (SG) and the gastric plication (GP) techniques. Rats submitted to SG showed a significant decrease in body weight gain when compared with sham-operated control animals, and this difference was similar to food-restricted rats (pair-fed), suggesting that the weight loss was due to food restriction. Rats submitted to GP displayed a significant decrease in body weight, and presented a lower relative body fat content when compared with the control groups. These animals did not present the typical increase in ghrelin levels that follow weight loss, which supports the hypothesis that weight loss observed after GP might not depend solely on food restriction. We hypothesized that the absence of rise in ghrelin levels could be essential in a sustained weight loss process. Thus, we tried to mimic it in a pharmacological, less invasive way. An immuneconjugate composed of the NS1 protein of the blue tongue virus and ghrelin, was used to immunize normal weight and with diet induced obesity (DIO) c57BL6 mice. The immuneconjugate was able to induce the production of specific anti-ghrelin antibodies. Vaccinated normal weight animals presented a significant decrease in cumulative food intake when compared to the controls, and DIO mice presented a significant decrease in food intake in the first 24hours after immunization. Vaccinated animals presented a significant increase in energy expenditure. DIO mice show a significant decrease in Npy expression, which means there is a decrease in the orexigenic signalling. However there were no differences in weight loss. Finally, we also evaluated the efficiency of a natural dietary supplement, OBEX®, in achieving weight loss. OBEX®, administered daily to mice fed with a high fat diet (HFD), was able to significantly decrease the weight gain due to the HFD, which is exclusively due to loss of fat mass. There were no differences in food intake. Animals treated with OBEX® present increased metabolic rate, with increased interscapular temperature, energy expenditure and respiratory quotient. As OBEX® appears to act directly in the adipose tissue, its effect was also evaluated in 3T3-F442A cells. The results show that OBEX® has a triple effect in this cell line decreasing proliferation, blocking differentiation and decreasing the lipid load in mature adipocytes, which confirms the general decreasing effect in the quantity of adipose tissue that was seen in the in vivo studies.