Herein, although ANGPTL8 under physiological conditions had no influence on either baseline Akt/GSK3β activation or cardiac structure and function, in the Ang II- or TAC-induced pathological cardiac hypertrophy model, increased p-Akt levels in the heart were observed and further increased following ANGPTL8 knockout in mice, leading to the deterioration of pathological cardiac hypertrophy. The gene discussed is GSK3B; the disease is cardiac hypertrophy.