Long-Term Casein-Bound Lactulosyllysine Consumption\nInduced Nonobese Nonalcoholic Fatty Liver Disease by Promoting Carbonyl\nGlycation in the Liver of C57BL/6 Mice

Lactulosyllysine (LL) is abundant\nin thermally processed dairy\nproducts, with its concentration increasing in response to more intense\nheat treatment. However, there are limited studies on the potential\nharmful effects of LL on human health. This study investigated the\nnegative impact of casein-bound LL on liver health by feeding healthy\nC57BL/6 mice diets containing varying levels of casein-bound LL. After\n16 weeks of LL diet administration, mice exhibited a nonobese nonalcoholic\nfatty liver disease (NONAFLD) phenotype, characterized by reduced\nbody weight gain, hypolipidemia, and intrahepatic lipid accumulation.\nNontarget metabolomic analysis showed that casein-bound LL induced\nalterations in plasma levels of compounds associated with lipid degradation.\nMechanistically, casein-bound LL may impair the function of 5′-adenosine\nmonophosphate-activated protein kinase and apolipoprotein B100 by\ninducing dicarbonyl stress, thereby promoting carbonyl glycation in\nthe liver. Consequently, the long-term consumption of LL-rich dairy\nproducts may be a contributing factor to the risk of developing NONAFLD.