Effects of Aerobic Exercise on Angiotensin II-induced Hepatic Injury and CLK2 Expression

Abstract

(Purpose) This study examined whether angiotensin II (Ang II) induces hepatic injury and alters Cdc2-like kinase 2 (CLK2) signaling as modulated by aerobic exercise. (Methods) Male C57BL/6 mice were assigned to Ctrl, Ang II, or Ang II with low- or high-intensity exercise groups. Ang II was administered for four weeks with concurrent treadmill exercise. Hepatic expression of CLK2, Akt, phosphorylated Akt, PGC-1α, inducible nitric oxide synthase (iNOS), and inflammatory markers was assessed using Western blotting. Histological injury was evaluated using hematoxylin and eosin staining. (Results) Ang II increased hepatic CLK2 expression and induced mild hepatocellular injury. Hepatic iNOS did not differ significantly between Ctrl and Ang II, despite a modest numerical increase. Both exercise groups showed lower iNOS than Ang II (Ang II; LIE, p<0.0001; HIE, p<0.01). The p-Akt/Akt ratio was lower in Ang II+HIE than in Ang II (p<0.001) but did not differ between Ctrl and Ang II, indicating that high-intensity exercise altered hepatic Akt phosphorylation under Ang II exposure. PGC-1α, IL-6, and TNF-α were unchanged. (Conclusions) Ang II disrupts hepatic molecular homeostasis and induces mild liver injury. Aerobic exercise mitigates Ang II–induced hepatic alterations accompanied by reduced CLK2 expression and iNOS.