Effect of human milk oligosaccharide on the liver-skeletal muscle axis in streptozotocin-induced metabolic stress.

Type 1 diabetes mellitus is characterized by insulin deficiency, hyperglycemia, and systemic metabolic and inflammatory disturbances that lead to multi-organ injury. Building on prior evidence that 6'-sialyllactose (SL), a sialylated human milk oligosaccharide, exerts anti-inflammatory and metabolic benefits, we investigated whether SL mitigates streptozotocin (STZ)-induced metabolic dysfunction and tissue injury in vivo. Male ICR mice were pretreated with SL (25 or 75 mg/kg) prior to STZ administration. STZ challenge markedly increased serum glucose levels, disrupted hepatic enzyme profiles, impaired protein metabolism, and induced liver apoptosis and inflammation. SL pretreatment significantly improved glucose homeostasis, normalized liver enzyme activities and serum protein indices, reduced hepatic caspase-3 activation, and suppressed pro-inflammatory cytokine expression in the liver and skeletal muscle. Mechanistically, SL restored AMPK-Akt-mTOR signaling in metabolic tissues. Collectively, these data demonstrate that SL confers systemic metabolic protection against STZ-induced diabetes, highlighting its potential as a therapeutic or preventive agent targeting inflammatory and metabolic pathways.