Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

BACKGROUND: Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. AIM: To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). METHODS: By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. RESULTS: After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. CONCLUSION: Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

[Effects of different paddy-upland multiple cropping rotation systems on soil organic carbon and its fractions in paddy field]. / ä¸åŒæ°´æ—±å¤ç§è½®ä½œæ–¹å¼å¯¹ç¨»ç”°åœŸå£¤æœ‰æœºç¢³åŠå ¶ç»„åˆ†çš„å½±å“.

The variations of soil organic carbon and its fractions in different paddy-upland multiple cropping rotation systems were evaluated in field trials in two consecutive years. During paddy-upland multiple cropping rotations conducted over 2 years, the content of soil total organic carbon (TOC) first increased and then decreased. The content of readily oxidized organic carbon (ROC) was highest at the rice tillering stage and lowest at the mature stage. The soil microbial biomass carbon (SMBC) was highest at the tillering stage. The dissolved organic carbon (DOC) content was highest at the mature stage. The maximum and minimum differences were at the booting stage and mature stage for TOC content, at the greening stage and booting stage for ROC content, at the mature stage and the greening stage for DOC content, at the tillering stage and the greening stage for SMBC, respectively. The soil TOC and DOC contents showed the largest variations in the 'winter fallow-early rice-late rice → winter fallow-early rice-late rice' rotation. The soil ROC content showed the largest variation in the 'milk vetch-early rice-late rice → rape-peanut-late rice' rotation. The maximum variation of SMBC was in the 'vegetables-peanut/corn-late rice → milk vetch-early rice-late rice' rotation. The 'potato-maize/soybean-late rice → vegetables-peanut/corn-late rice' rotation resulted in higher soil TOC content at the booting stage. The pattern of 'milk vetch-early rice-late rice → oil rape-peanut-late rice' led to higher soil ROC contents in the early and middle growth stages of late rice. In the 'rape-peanut-late rice → potato-maize/soybean-late rice' rotation, the highest DOC contents were at the greening stage and the mature stage, and the highest SMBC were at the booting stage and the heading stage, respectively. All these diffe-rences were significant. The rank the contents of soil organic carbon fractions from highest to lowest followed the order: TOC>ROC>SMBC>DOC. The results suggested that paddy-upland multiple cropping rotation systems could increase the contents of soil organic carbon and its fractions and improve soil quality and fertility.