Lactobacillus acidophilus NX2-6 Improved High-Fat Diet-Induced Glucose Metabolism Disorder Independent of Promotion of Insulin Secretion in Mice

High-fat diet (HFD) contributes to metabolic inflammation and glucose metabolism disorder, thereby resulting in the pathogenesis of metabolic syndrome. Accumulating evidence has revealed that some probiotics could improve HFD-induced metabolic inflammation and glucose metabolism disorder. Our previous study has discovered that Lactobacillus acidophilus NX2-6 exhibited in vitro lipid-lowering, antioxidative, and anti-inflammatory activities. This study mainly investigated whether L. acidophilus NX2-6 improved HFD-induced glucose metabolism disorder. The results exhibited that L. acidophilus NX2-6 effectively reduced blood glucose levels and improved glucose tolerance by activating the insulin signaling pathway, promoting glucose uptake, glycolysis, and intestinal gluconeogenesis and suppressing hepatic gluconeogenesis, independent of regulation of glycogen synthesis in the liver and muscle. Enhanced insulin sensitivity was associated with L. acidophilus NX2-6-mediated suppression of inflammatory cascades in the target organs. Meanwhile, L. acidophilus NX2-6 also improved hepatic energy metabolism via the FGF21/AMPKα/PGC-1α/NRF1 pathway. However, L. acidophilus NX2-6 did not affect apoptosis, pyroptosis, inflammation, and endoplasmic reticulum stress in the pancreas of HFD-fed mice. In conclusion, our results indicated that L. acidophilus NX2-6 improved glucose metabolism disorder through enhancing insulin sensitivity, suppressing metabolic inflammation, and promoting energy expenditure.