Changes of Ghrelin/GOAT axis and m TOR pathway in the hypothalamus after sleeve gastrectomy in obese

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:fairstone
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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), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 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). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, 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. 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 ) rats, 6 wk of age, fed with high-sugar and high fat fodder for 2 mo plus intraperitoneal injection of streptozotocin were divided into three groups: non-operation group (S0 group, n = 10), sham operation group (SG), 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, pm TOR and p-S6) were measured in the hypothalamus .RESULTS SG can significantly improve metabolic sympathy toms 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), but unchanged AG (153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng / L, respectively, P> 0.05) , the ratio of AG / TG ​​further increased in SG group (0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P <0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin ( 0.63 ± 0.12 vs 0.5 ± 0.11, P <0.05) and GOAT (0.96 ± 0.09 vs 0.87 ± 0.08, P <0.05), but did not change NPY mRNA expression (0.61 ± 0.04 vs 0.65 ± 0.07, P> 0.05) the hypothalamus. The protein levels of p-Akt, pm TOR and p-S6 were higher in the SG group, which indicates 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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