Changes of Ghrelin/GOAT axis and mTOR pathway in the hypothalamus after sleeve gastrectomy in obese type-2 diabetes rats

Abstract

AIMTo 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.METHODSA 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.RESULTSSG 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.CONCLUSIONThe reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.

Sleeve gastrectomy improves cardiac function and glucose-lipid metabolism disorder in obese rats induced by a high-fat and high-sugar diet

“…Additionally, consistent with previously published data [21], severe impairments in liver metabolic function and lipid metabolism were observed in obese rats, which were significantly alleviated by SG. Indeed, the protective effects of SG against obesity have been reported in several studies [22][23][24], Endocrine Journal Advance Publication further confirming our findings in the present study.…”

Potential mechanisms of sleeve gastrectomy for reducing weight and improving metabolism in patients with obesity

“…In an experimental obese T2D rat model, a previous study found that the downregulation of ghrelin and activation of the hypothalamic mTOR pathway could produce an opposite effect on food intake after SG surgery. In addition, activation of the mTOR pathway accounted for increased NPY levels after SG [29]. Previous studies found that the nervous system, like the vagus nerve, is involved in the regulation of reduced appetite and food intake after the SG procedure; the gut-brain axis may play a vital regulatory role [30].…”

Surgical correction of metabolic syndromes in rats: methodological aspects

“…Для удобства дальнейших манипуляций под заднюю стенку желудка подкладывается сложенная в несколько раз салфетка. Операция ПРЖ заключается в удалении значительной части желудка (около 70%) с формированием из оставшейся части узкой трубки [23].…”