Probiotics protect against hepatic steatosis in tris (2-chloroethyl) phosphate-induced metabolic disorder of mice via FXR signaling.

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.

Glucosamine induces increased musclin gene expression through endoplasmic reticulum stress-induced unfolding protein response signaling pathways in mouse skeletal muscle cells.

Glucosamine (GlcN) is a dietary supplement that is widely used to promote joint health. Reports have demonstrated that oral GlcN adversely affects glucose metabolism. Here, we found that oral administration of GlcN induced insulin resistance (IR) and increased plasma glucose levels in mice. Musclin is a muscle-secreted cytokine that participates in the development and aggravation of diabetes. In this study, we found that increased expression of the musclin plays a pathogenic role in GlcN-induced IR in mice. Additional in vivo and in vitro studies showed that 4-PBA inhibited GlcN-induced endoplasmic reticulum (ER) stress and reduced musclin expression, indicating that ER stress might be closely linked to musclin expression. Moreover, the inhibition of musclin gene expression was also observed when sh-RNAs and small molecular compound inhibitors inhibited ER stress-induced PERK and IRE1-associated unfolding protein response (UPR) signaling pathways, and the CRISPR/Cas9 genome editing technology knockout the ATF6-associated UPR pathway in C2C12 myotubes cells. Silencing of the expression of musclin effectively relieved GlcN-affected phosphorylation of Akt, glucose intake and glycogen synthesis. These results suggest that GlcN increased musclin gene expression though UPR, and musclin represents an important mechanism underlying GlcN-induced IR in mice.