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.