Published online Sep 14, 2017. doi: 10.3748/wjg.v23.i34.6231
Peer-review started: March 9, 2017
First decision: April 21, 2017
Revised: May 2, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: September 14, 2017
Processing time: 190 Days and 14.2 Hours
To examine the changes of the ghrelin/ghrelin O-acyltransferase (GOAT) axis and the mammalian target of rapamycin (mTOR) pathway in the hypothalamus after sleeve gastrectomy.
A total of 30 obese type-2 diabetes Sprague-Dawley (SD) rats, 6 wk of age, fed with high-sugar and high-fat 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 mRNA expression of preproghrelin, GOAT and neuropeptide Y (NPY), and protein expression of ghrelin, GOAT, GHSR and the mTOR pathway (p-Akt, p-mTOR and p-S6) were measured in the hypothalamus.
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 mRNA 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) in the hypothalamus. The protein levels of p-Akt, p-mTOR and p-S6 were higher in the SG group, which indicated that the hypothalamic mTOR pathway was activated after SG at the postoperative week 8.
The reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.
Core tip: Recent studies have demonstrated a complex relationship between ghrelin, ghrelin O-acyltransferase (GOAT) and the mammalian target of rapamycin (mTOR) pathway. In our study, we examined the changes of the ghrelin/GOAT axis and the mTOR pathway in the hypothalamus after sleeve gastrectomy (SG). The mRNA and protein levels of ghrelin and GOAT decreased after SG, while NPY mRNA expression did not change. We also found that SG increased the protein levels of p-Akt, p-mTOR and p-S6. The reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake. These findings might explain the weight, glucose and food intake regain after SG.