Effects Of Nesfatin-1 On Gastric Emptying And Contractility Of Gastric Smooth Muscle Strips In Obese Rats

Found by the Oh IS, nesfatin-1is a new feeding regulatory peptides, their precursors NEFA gene encoding the420amino acid peptide (nucleobindin Ⅱ, referred NUCB2). It widely distributes, mainly in the hypothalamus and peripheral digestive system, where the expression in the gastric mucosa NUCB2is10times higher than the center. Nesfatin/NUCB2includes a signal peptide, which consists of24amino acids and a protein structure, which consists of396amino acids. Under the action of the prohormone-converting enzyme (prohormone convertase, PC), nesfatin/NUCB2can be cleaved into three fragments, respectively, nesfatin-1, nesfatin-2and nesfatin-3. Inject the three fragments in intracerebroventricular, only nesfatin-1can dose-dependently inhibit food intake in rats. Injection of nesfatin-1antibody (nesfatin Ab-24) into intracerebroventricular, can significantly increase food intake in rats. At present, there is no clear finding about the receptor of nesfatin-1. When talking about the feeding inhibition mechanism of nesfatin-1, Oh IS and colleagues first reported in Nature in2006that even if mutations happened in the leptin receptor Zucker rats, nesfatin-1still can inhibit feeding. The a-MSH receptor (MC4-R) blockers may block the nesfatin-1inhibitory effect of feeding. a-MSH injected into icv causes the paraventricular nucleus NUCB2mRNA expression increased, thus nesfatin-1inhibitory effect is mediated through the MSH system (melanocortin signalling).. Currently on nesfatin-1in the pathophysiology of obesity in rats reported no correlation.Obesity seriously affect the quality of modern life, is one of the risk factors of hypertension, coronary heart disease, diabetes and other common diseases, so prevention and treatment of obesity has great significance. In this study, normal and obese rats were micro-injected of nesfatin-1through vagal complex (dorsal vagal complex, DVQto study its impact on gastric emptying. And gastric smooth muscle in vitro was treated with different concentrations of nesfatin-1. to observe rat smooth muscle contraction activity. We study obese rat feeding effect, in order to further reduce obesity and provide a theoretical help.Objective By creating obese rats, we observe the normal and obese rats gastric emptying through the central injection of nesfatin-1. And in vitro treated with different concentrations of nesfatin-1; we observe normal and obese rats gastric smooth muscle contraction before and after administration.Methods Feed the rats with a high-fat diet for6weeks, then observe their body weights and obesity index.Compare them with the normal diet groups. Put a catheter into each rat’s brain--dorsal vagal complex(DVC), then inject a series concentration of nesfatin-1 (0.5/μmol/L、5/μmol/L、50/μmol/L) into the center(DVC). Gastric emptying was determined by the phenol red method comparing with the normal groups. Make up gastric fundus and gastric body circular smooth muscle strips, and put them in constant temperature baths. Connect polygraph with tension transducer to record the spontaneous contraction of the rat stomach fundus and gastric body circular smooth muscle compared to vehicle. We observe the muscle contraction in different concentrations of nesfatin-1(0.026/μmol/L,0.26/μmol/L, and2.6μmol/L) under the action of acetylcholine (Ach).Results Compared with the control group, low concentration of nesfatin-1(0.5μmol/L) can inhibit gastric emptying in normal rats (q=3.86, P<0.05), but can’t inhibit gastric emptying in obese rats (q=2.95, P>0.05). Medium and high concentration of nesfatin-1(5.0/μmol/L,50μmo/L) inhibit gastric emptying in normal rats (q=12.09, P<0.01;q=13.70, P0.01) and obese rats (q=7.45, P0.01;q=8.89, P<0.01). Nesfatin-1can inhibit the normal and obese rat gastric smooth muscle strips, low, medium and high concentration groups compared with the control group differences were statistically significant(q=3.93～15.72, P<0.05～0.01).Conclusion Nesfatin-1inhibits gastric emptying in normal and obese rats, gastric emptying rate decreases with increasing drug concentration. Nesfatin-1inhibits acetylcholine induced obese rat gastric smooth muscle contraction activities, with concentration increasing of nesfatin-1, its inhibitory enhanced. Under the same concentration, the inhibition of nesfatin-1is stronger in normal rats than in obese ones.