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Short-chain fatty acids (SCFAs), which are metabolites derived from the fermentation of dietary fibre by the gut microbiota, are important for host metabolic health. There is interest in probiotics for their beneficial effects on metabolic disorders, such as obesity, but the underlying mechanisms remain largely unknown. In this study, we evaluated whether Bifidobacterium animalis subsp. lactis GCL2505 (GCL2505), a probiotic strain capable of proliferating and increasing SCFA levels in the gut, exerts anti-metabolic syndrome effects via the SCFA receptor G protein-coupled receptor 43 (GPR43). A GCL2505 treatment suppressed body fat accumulation, improved glucose tolerance, and enhanced systemic fatty acid oxidation in high-fat diet (HFD)-fed wild type (WT) mice, whereas these effects were not observed in HFD-fed Gpr43 knockout (Gpr43−/−) mice. Caecal and plasma acetate levels were elevated by GCL2505 in WT and Gpr43−/− mice, but the negative correlation between plasma acetate levels and body fat accumulation was observed only in WT mice. We further demonstrated that GCL2505 suppressed insulin signalling in the adipose tissue via GPR43. These results suggested that increases in SCFA levels in response to GCL2505 enhance host energy expenditure, which decreases fat accumulation via activated GPR43. [ABSTRACT FROM AUTHOR]

Background:S-equol, which is enantioselectively produced from daidzein by gut microbiota, has been suggested as a chemopreventive agent against type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain unclear.Objective: We investigated the effects of S-equol on pancreatic β-cell function.Methods: β-Cell growth and insulin secretion were evaluated with male Institute of Cancer Research mice and isolated pancreatic islets from the mice, respectively. The mechanisms by which S-equol stimulated β-cell response were examined in INS-1 β-cells. The effect of S-equol treatment on β-cell function was assessed in low-dose streptozotocin-treated mice. S-equol was used at 10 μmol/L for in vitro and ex vivo studies and was administered by oral gavage (20 mg/kg, 2 times/d throughout the experimental period) for in vivo studies.Results:S-equol administration for 7 d increased Ki67-positive β-cells by 27% (P < 0.01) in mice. S-equol enantioselectively enhanced glucose-stimulated insulin secretion in mouse pancreatic islets by 41% (P < 0.001). In INS-1 cells, S-equol exerted stronger effects than daidzein on cell growth, insulin secretion, and cAMP-response element (CRE)-mediated transcription. These S-equol effects were diminished by inhibiting protein kinase A. The effective concentration of S-equol for stimulating cAMP production at the plasma membrane was lower than that for phosphodiesterase inhibition. S-equol-stimulated CRE activation was negatively controlled by the knockdown of G-protein α subunit group S (stimulatory) and positively controlled by that of G-protein-coupled receptor kinase-3 and -6. Compared with vehicle-treated controls, S-equol gavage treatment resulted in an increase in β-cell mass of 104% (P < 0.05), a trend toward high plasma insulin concentrations (by 118%; P = 0.06), and resistance to hyperglycemia after streptozotocin treatment (78% of AUC after glucose challenge; P < 0.01). S-equol administration significantly increased the number of Ki67-positive proliferating β-cells by 62% (P < 0.01) and decreased that of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic β-cells by 75% (P < 0.05).Conclusions: Our results show that S-equol boosts β-cell function and prevents hypoglycemia in mice, suggesting its potential for T2DM prevention. [ABSTRACT FROM AUTHOR]