Lactococcus lactis KF140 Ameliorates Nonalcoholic Fatty Liver Disease Induced by N^ε-Carboxymethyl-Lysine and High-Fat Diet

Scope: Long-term consumption of excessive dietary advanced glycation end-products such as N^ε-carboxymethyl-lysine (CML), which are produced by the Maillard reaction during food thermal processing, leads to nonalcoholic fatty liver disease (NAFLD) along with high fat consumption. The study previously finds that administration of Lactococcus lactis KF140 (LL-KF140) detoxifies CML by decreasing CML absorption both in a rat model and clinical trial. Methods and results: The present study evaluates the ameliorative effect of LL-KF140 on NAFLD and fatty liver-related biomarkers in a mouse model induced by CML and high fat. LL-KF140 is orally administered to mice at a concentration of 1 × 10⁷ or 1 × 10⁸ colony-forming unit (CFU) per mouse for 8 weeks. LL-KF140 administration ameliorates the NAFLD-related symptoms by reducing body weight and fat mass gain along with levels of serum aspartate transaminase, alanine transferase, and lipids as well as glucose intolerance and insulin resistance in CML-treated mice. In addition, histological analysis including staining and western blotting shows that LL-KF140 suppresses the lipogenesis pathway and CML absorption, thereby suppressing CML-induced NAFLD. Conclusion: These findings suggest that LL-KF140 attenuates dietary CML-induced NAFLD by suppressing the de novo lipogenesis pathway, and it may be used as a probiotic strain.