Obesity-related breast cancer diseases characterization of adiponectin peptidomimetics

Abstract

Adiponectinis an important adipokine, secreted mainly by adipose tissue and existed as different oligomeric forms, including trimer, hexamer and high molecular weight (HMW) oligomers. The multifunctional activities of this protein are closely related to the circulating concentration of HMW adiponectin. In the first part of the study, a series of glycosylated peptides were synthesized based on the sequence of collagenous domain of full length human adiponectin. The peptide mimetics exhibited significant anti-proliferative activity in MDA-MB-231 breast cancer cell line. The oligomeric distributions of the mimetic peptides showed distinctive pattern, indicating that the glycans at different lysine residues regulated the oligomer formation, in turn influencing the anti-cancer activity of adiponectin. These cretion and assembly of adiponectin from adipocytes was regulated by the chaperones in endoplasmic reticulum (ER). The circulating level of adiponectin was decreased under obesity-induced ER stress condition. In the second part of the study, IgM-derived peptides were designed to facilitate the secretion and HMW oligomer formation of adiponectin, thus replenishing the shortage of serum adiponectin concentration and mitigating the related metabolic disorders. Long-term treatment of IgM-derived peptides could reduce cholesterol and triglyceride level in serum and liver, improve insulin sensitivity, reduce body fat mass, and increase serum adiponectin in dietary obese mice. In summary, the study demonstrated that peptides derived from adiponectin represent potential biotherapeutic agents for obesity-related metabolic and cancer diseases.