Mechanism of long-term maintenance of weight loss and blood glucose homeostasis after Roux-en-Y gastric bypass

Objective To explore the mechanism of long-term maintenance of weight loss and blood glucose homeostasis after Roux-en-Y gastric bypass(RYGB). Methods 12 weeks old male Sprague Dawley (SD) rats were used as animal models and randomly divided into Sham group (n=22), RYGB group (n=12) and pancreatectomy group (n=10), and were with normal diet or high-fat diet for 8 weeks. The levels of insulin secretion, glucose infusion rate, body weight and blood glucose were measured, and the metabolic pathways of adipose tissue were detected by gene chip and western blot. The t test and variance analysis were used to compare the difference among the three groups. Results Compared with Sham group, the fasting and glucose stimulated plasma insulin in SD rats were significantly reduced after metabolic surgery [(1.3±0.2) vs (0.6±0.1) ng/ml, t=3.6, P<0.01; (4.1±0.4) vs (2.1±0.3) ng/ml, t=4.3, P<0.01]. In addition, fasting insulin and body weight could be maintained at a low level for a long time on high fat diet [(3.1±0.3) vs (0.7±0.1) ng/ml, t=8.1, P<0.01; (453±11) vs (349±6) g, t=8.5, P<0.01]. The mechanism study found that insulin signal pathway of adipose tissue was inhibited (1.0±0.1 vs 0.5±0.1, t=6.4, P<0.01), fatty acid synthesis and decomposition were decreased, and the expression of adenosine monophosphate-activated protein kinase was enhanced (1.0±0.1 vs 1.4±0.1, t=4.0, P<0.01). After the removal of most pancreatic tissues, the levels of fasting plasma insulin and glucagon were reduced 71.7% and 68.0% respectively [(1.10±0.10) vs (0.30±0.04) ng/ml, t=7.5, P<0.01; (16.2±0.8) vs (5.2±0.9) pmol/L, t=9.1, P<0.01], but the fasting blood glucose was not significantly increased, and the body weight was significantly lower in the normal diet and high-fat diet group compared to sham group [(434±13) vs (389±5) g, t=3.1, P<0.05; (548±16) vs (433±11)g, t=6.0, P<0.01]. Conclusions RYGB can maintain low body weight and blood glucose homeostasis for a long time by reducing energy intake and avoiding hyperinsulinemia. The mechanism is closely related to the inhibition of fat synthesis and metabolism, and the enhancement of catabolism. Key words: Obesity; Insulin; Metabolic surgery; Adenosine monophosphate-activated protein kinase