Emerging Immnunohistochemical evidence for Direct Peripheral Control of Endocannabinoids on the Gastrointestinal Tract and Pancreas of Obese (fa/fa)and Lean Zucker Rats (Pathophysiological Implications)

This research has the objective to investigate immunohistochemical expression of CB1 receptor and its probable changes in Gastroenteropancreatic system (GEP) of obese and lean Zucker rats and understand the endocannabinoid pathophysiological implications in the obesity. Male obese (fa/fa) and lean Zucker rats 6 weeks old were obtained from Harlan Italy Srl; the rats were sacrificed at 8, 12 and 16 weeks old. Normal rats also were sacrificed. Specimens of stomach, jejunum-ileum and pancreas were fixed in Bouin’s mixture and embedded in paraffin; obtained sections were processed with anti-CB1 (Biosource Europe SA) by Streptavidin-Biotin-Complex Method. The findings show that CB1 receptor is expressed not only in enteric neurons as documented by earlier studies up to now but more widely and with stronger intensity in obese animals compared with their lean counterparts by several structures of gastrointestinal tract (epithelium, glands, endocrine cells and immune cells of villi stroma). In obese Zucker rats pancreas unlike the normal rats where the CB1 receptor is essentially expressed by A-cells, the CB1 immunoreactivity even extends with higher intensity to B-cells. It is concluded that GEP System represents a new and wide peripheral target of EC action that have a direct autocrine, endocrine-paracrine and neurocrine control on many functions of GEP. In addition in GEP of obese Zucker rats in comparison with lean ones, the CB1 receptor is overexpressed and consequently the peripheral endocannabinoid system is upregulated and negatively modulated by leptin. It may contribute to increase hyperphagia, body weight and hyperglycaemia.