Lysyl-Aspartic Acid Derivatives as Model Compounds of Growth Hormone to Induce Lipolysis

Abstract

The effects of derivatives containing Lys-Asp sequences on growth-hormone-mediated lipolysis were examined for fat cells isolated from rat epididymal adipose tissue. A dipeptide, Lys-Asp, had a weak but distinct ability to induce lipolysis and inhibit growth-hormone-mediated lipolysis. Among the derivatives tested, Lys(Z)-Asp(OEt)-OEt (6d), Lys(Z)-Asp(OC₄H₉)-OC₄H₉ (6e), Lys(Z)-Asp(OC₈H₁₇)-OC₈H₁₇ (6f), C₇H₁₅CO-Lys(Z)-Asp (4b), and C₁₅H₃₁CO-Lys(Z)-Asp (4c) had a fairly high lipolytic activity. The derivatives 6e, 6d and 4c inhibited growthhormone-mediated lipolysis. A derivative, C₁₅H₃₁CO-Lys-Asp(OMe)-OMe (3c), had no lipolytic activity but strongly inhibited for growth-hormone-mediated lipolysis. It is suggested that charge groups in the Lys-Asp derivatives are responsible for lipolytic action and the hydrophobic hydrocarbon chains in the derivatives enhance the ability to induce lipolysis or inhibit the gorwthhormone-mediated lipolysis.