Obesity is a multifactorial disease generated by an alteration in balance between energy intake and expenditure, also dependent on genetic and non-genetic factors. This pathology has reached epidemic proportions, hence, novel strategies to fight are needed to be found. Recently, the obese adult zebrafish was considered an experimental model with pathophysiological pathways similar to mammalian obesity. Therefore we used a Diet Induced Obesity (DIO) adult Zebrafish to analyse in overfed fish (OF) the increase of body weight (BW) and body mass index (BMI) as well as accumulation of adipose tissue in the visceral and subcutaneous zones. Numerous data demonstrate that the BDNF/TrkB system has a fundamental role in the control of food intake and body weight. Therefore, the variation of body weight and body mass index and morphometry of visceral and subcutaneous fat depots were analysed. Quantitative PCR and immunohistochemistry for both BDNF and TrkB were used to determine changes in their levels in the brain and gastro-intestinal tract of an experimental zebrafish model of diet-induced obesity. Overfed animals showed increased weight and body mass index as well as accumulation of adipose tissue in the visceral, subcutaneous areas. These changes were concomitant with decreased levels of BDNF mRNA in the gastrointestinal tract and increased expression of TrkB mRNA in the brain. These results suggest an involvement of the BDNF/TrkB system in the regulation of food intake and energy balance in zebrafish, as in mammals. Recently, numerous natural and synthetic compounds have been tested in diet-induced obese animal models, to counteract obesity. For this purpose, in our studies, the effects of melatonin administration (that control energy balance by activating or inhibiting appetite-related peptides), Citrus sinensis and Vitis vinifera (flavonoid-rich extract with anti-inflammatory and anti-oxidant action) in control-fed and overfed zebrafish were tested. The variation of body weight and body mass index and morphometry of visceral and subcutaneous fat depots were analysed and the orexigenic (Ghrelin, orexin, NPY) and anorexigenic (leptin, POMC) genes expression were evaluated with qPCR analyses. In obese zebrafish all the natural compounds significantly lowered both BW and BMI values and the visceral adipose tissue too. Moreover, adipocyte cell size in OF groups in both visceral and subcutaneous adipose tissues was significantly reduced, as well as cell number in OF fish. Finally, they modulate some appetite-related genes such as leptin, ghrelin, orexin, pro-opiomelanocortin and neuropeptide Y, in both gut and brain. These studies add new insights into the anti-obesity effects of natural compounds, suggesting their role as weight management agent, through a lipolytic action linked to a restoration of the appetite-regulating genes expression.
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