Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

BACKGROUND & AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation. METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5-/-) and intestinal-specific farnesoid X receptor null (FxrΔ/E) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/-) mice on chow diet were characterized following GB-IL. RESULTS: GB-IL induced weight loss and improved oral glucose tolerance in Tgr5-/-, but not FxrΔ/E mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r-/- mice. CONCLUSIONS: Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

Phthalocyanine functionalized poly(glycidyl methacrylate) nano-assemblies for photodynamic inactivation of bacteria.

The design of novel antibacterial materials has attracted increasing attention for combating bacterial infections. Herein, we conjugated zinc(ii) monoamino phthalocyanine (ZnMAPc) to poly(glycidyl methacrylate) (PGMA) via a ring-opening reaction, and the excess epoxy groups were scavenged by ethylenediamine (ED). The resultant macro-photosensitizer (PGED-Pc) can be easily dispersed in aqueous solution to form self-assembled nanoparticles and generate reactive oxygen species for inactivation of bacteria when exposed to light illumination. We found that the photodynamic pathway for the generation of singlet oxygen (1O2) was strongly inhibited in aqueous solution, and the major components for the inactivation of bacteria were superoxide anion radicals (˙O2-) and hydrogen peroxide (H2O2), which could result in the disruption of bacterial envelopes, the inactivation of vital enzymes, and the degradation of genomic DNA. PGED-Pc exhibited potent photodynamic antibacterial activity, with minimum bactericidal concentration (MBC, defined as 99.9% inactivation of bacteria) values of 128 µg mL-1 for Escherichia coli (E. coli) and 4 µg mL-1 for Staphylococcus aureus (S. aureus). As a proof-of-concept, the PGED-Pc nano-assemblies in aqueous solution can be readily immobilized on glass slides via a Schiff-base reaction, and impose potent photodynamic antibacterial activity upon light illumination. This work unveils a promising strategy for the engineering of self-sterilizing surfaces to combat bacterial infections.