Lactate Protects Intestinal Epithelial Barrier Function from Dextran Sulfate Sodium-Induced Damage by GPR81 Signaling.

The dysregulation of the intestinal epithelial barrier significantly contributes to the inflammatory progression of ulcerative colitis. Recent studies have indicated that lactate, produced by gut bacteria or derived from fermented foods, plays a key role in modulating inflammation via G-protein-coupled receptor 81 (GPR81). In this study, we aimed to investigate the potential role of GPR81 in the progression of colitis and to assess the impact of lactate/GPR81 signaling on intestinal epithelial barrier function. Our findings demonstrated a downregulation of GPR81 protein expression in patients with colitis. Functional verification experiments showed that Gpr81-deficient mice exhibited more severe damage to the intestinal epithelial barrier and increased susceptibility to DSS-induced colitis, characterized by exacerbated oxidative stress, elevated inflammatory cytokine secretion, and impaired expression of tight-junction proteins. Mechanistically, we found that lactate could suppress TNF-α-induced MMP-9 expression and prevent the disruption of tight-junction proteins by inhibiting NF-κB activation through GPR81 in vitro. Furthermore, our study showed that dietary lactate could preserve intestinal epithelial barrier function against DSS-induced damage in a GPR81-dependent manner in vivo. Collectively, these results underscore the crucial involvement of the lactate/GPR81 signaling pathway in maintaining intestinal epithelial barrier function, providing a potential therapeutic strategy for ulcerative colitis.

Effects of amylose and amylopectin molecular structures on starch electrospinning.

The role of amylose content in electrospinning starch nanofibres is well understood, but that is not the case for the roles of the molecular structures of amylose and amylopectin. Here, correlations between starch molecular-structure parameters and electrospinnability evaluation indices (average droplet number, average bead number, and average fibre diameter) and dope properties (shear viscosity, conductivity, and surface tension) were examined. Starches with lower amounts of short amylopectin chains, higher amounts of either/or long amylopectin chains and/or lower degree of branching showed decreased viscosity of the electrospinning dopes, and resulted in a reduced average droplet number of electrospun fibre mats. The molecular sizes of amylose and whole starch, and the average degree of polymerization for amylose chains, all correlated with the shear viscosity and surface tension of dopes, and thus influenced the average fibre diameter. This expands the current understanding between amylopectin molecular structure and starch electrospinning, thereby assisting a better choice of starches for desired electrospinnability properties.

Dietary Lactate Supplementation Protects against Obesity by Promoting Adipose Browning in Mice.

Yogurt has been widely used in weight-loss foods to prevent obesity, but its molecular nature remains unclear. Lactate is a major ingredient of yogurt, while its cognate cell surface receptor GPR81 is highly expressed in adipose tissues in mammals. Here we hypothesized that dietary lactate supplementation might activate GPR81 to promote adipose browning. Studying mouse models, we observed that GPR81 was substantially lowered in adipose tissue of obese mice compared with that for lean ones, whereas its expression was markedly up-regulated by a ß3-adrenergic receptor (ß3-AR) agonist. The deficiency of GPR81 greatly attenuated experimental adipose browning and thermogenesis. Importantly, oral administration of lactate effectively induced adipose browning, enhanced thermogenesis, improved dyslipidemia, and protected mice against high-fat-diet-induced obesity. Mechanistically, p38 mitogen-activated protein kinase might serve as a key downstream effect or of GPR81. Collectively, our findings revealed a critical role of GPR81 in adipose browning and provided a new insight into obesity management by modulating lactate-GPR81 signaling axis.