Roux-en-Y gastric bypass surgery (RYGB) can achieve long-term remission of type 2 diabetes. However, the specific molecular mechanism through which this occurs has remained largely elusive. Bile acid signaling through the nuclear hormone receptor farnesoid X receptor (FXR) exerts beneficial effects after sleeve gastrectomy (VSG), which has similar effects to RYGB. Therefore, we investigated whether FXR signaling is necessary to mediate glycemic control after RYGB. RYGB or sham surgery was performed in high-fat diet-induced obese FXR-/- (knockout) and FXR+/+ (wild type) littermates. Sham-operated mice were fed ad libitum (S-AL) or by weight matching (S-WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance tests, insulin tolerance tests, and homeostatic model assessment of insulin resistance were performed. RYGB surgery decreases body weight and fat mass in WT and FXR-KO mice. RYGB surgery has similar effects on food intake and energy expenditure independent of genotype. In addition, body weight-independent improvements in glucose control were attenuated in FXR -/- relative to FXR +/+ mice after RYGB. Furthermore, pharmacologic blockade of the glucagon-like peptide-1 receptor (GLP-1R) blunts the glucoregulatory effects of RYGB in FXR +/+ but not in FXR -/- mice at 4 weeks after surgery. These results suggest that FXR signaling is not required for the weight loss up to 16 weeks after RYGB. Although most of the improvements in glucose homeostasis are secondary to RYGB-induced weight loss in wild type mice, FXR signaling contributes to glycemic control after RYGB in a body weight-independent manner, which might be mediated by an FXR-GLP-1 axis during the early postoperative period.

Cellulose dissolution is crucial for its regeneration and the application of its derivative materials. In this study, the dissolution of cellulose in γ-valerolactone (GVL), promoted by 1-ethyl-3-methylimidazolium acetate ([Emim]OAc), was investigated and 15 wt% α-cellulose was rapidly dissolved by the designed mixed organic electrolyte solvents (OESs) at 80 °C in 1 h. The rheological study indicated that the activation energy of dissolution is lower than that in pure [Emim]OAc, and the overlap concentration was determined to be C* = 1.7 wt%. The viscosity of the α-cellulose solution overlapped well with the complex viscosity, suggesting that the Cox–Merz law is valid therein. The potential of the solution for homogeneous derivatization through transesterification of α-cellulose with vinyl esters was also investigated at 80 °C in 4 h with a low vinyl ester/anhydroglucose unit (AGU) molar ratio of 3, achieving a cellulose laurate ester with a DS = 3.0, cellulose pivalate ester with a DS = 3.0 and cellulose chloroacetate ester with a DS = 1.43.

Background. The repair and regeneration of large bone defects represent highly challenging tasks in bone tissue engineering. Although recent studies have shown that osteogenesis is stimulated by periodic heat stress, the thermal regulation of osteogenic differentiation in ectomesenchymal stem cells (EMSCs) is not well studied. Methods and Results. In this study, the direct effects of periodic heat stress on the differentiation of EMSCs into osteoblasts were investigated. EMSCs derived from rat nasal respiratory mucosa were seeded onto culture plates, followed by 1h of heat stress at 41C every 7 days during osteogenic differentiation. Based on the results of the present study, periodic heating increases alkaline phosphatase (ALP) activity, upregulates osteogenic-related proteins, and promotes EMSC mineralization. In particular, increased YAP nuclear translocation and YAP knockdown inhibited osteogenic differentiation induced by heat stress. Furthermore, the expression and activity of transglutaminase 2 (TG2) were significantly increased after YAP nuclear translocation. Conclusion. Together, these results indicate that YAP plays a key role in regulating cellular proteostasis under stressful cellular conditions by modulating the TG2 response.