AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.
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