Endocrine Abstracts

Introduction: Angiopoietin-like protein 4 (Angptl4), also known as fast-induced adipose factor (Fiaf), is a glycoprotein which is known as a potent inhibitor of lipoprotein lipase. We have reported that hypothalamic Angptl4 is a novel anorexigenic molecule by inhibiting hypothalamic AMPK activity. In the present study, we investigated a potential role of Angptl4 in exercise-related physiology.

Methods: We determined changes in Angptl4 mRNA/protein levels along with phospho-total AMPK levels in leg skeletal muscle of mice following moderate strength prolonged running exercise (18 m/min for 50 min). We treated Angptl4 peptide in C2C12 skeletal muscle cells to test if Angptl4 can activate AMPK activity in skeletal muscle. Finally, we compared the effects of chronic running exercise (5–18 m/min for 50 min, five times/week for 2 weeks) on muscle AMPK activity and food intake of Angptl4 null mice and their wild littermates.

Results: Running exercise significantly increased Angptl4 mRNA and protein levels and AMPK phosphorylation in skeletal muscle. Treatment of Angptl4 in C2C12 cells significantly increased AMPK and ACC phosphorylation in a dose- and time-dependent manner. Exercise-induced AMPK activation in skeletal muscle was diminished in Angptl4 null mice. Chronic running exercise significantly reduced food intake in wild mice, but exercise-induced anorexigenic effect were blunted in Angptl4 null mice.

Conclusion: Our data have demonstrated a potential role of skeletal muscle Angptl4 in exercise-induced AMPK activation and exercise induced anorexia. Therefore, Angptl4 may mediate metabolic changes during exercise.