title: Metabolic effects of a stabilizing peptide fusion protein of leptin in normal mice.
abstract: Leptin is a protein hormone produced by adipocytes. It is secreted into the blood stream and plays a key role in regulating body energy homeostasis by inhibiting feeding behavior followed by decreased body weight. Because protein aggregation is a major problem in therapeutic proteins, we previously demonstrated that a stabilizing peptide (SP) fusion protein of leptin (SP-leptin) appeared to resist aggregation induced by agitation, freezing/thawing, or heat stress. In this study, we fused mouse leptin with the stabilizing peptide and compared the biological activities of leptin and SP-leptin in vivo using a male C57Bl mouse model and ex vivo using MCF7 breast cancer cell lines. Each group of mice was treated with saline, leptin, and SP-leptin for 20 days and the differences in body weight, food intake, abdominal fat contents, and TG concentration were measured. The SP-leptin appeared to decrease the body weight and food intake in male C57Bl mice more significantly than wild type leptin, and the SP-leptin treated MCF7 cells displayed better cell proliferation than leptin. As a consequence of decreased body weight, the SP-leptin treated mouse group showed decreased abdominal fat contents and low triglyceride (TG) concentration. Moreover, the SP-leptin treated mouse group had fewer lipid droplets in liver and reduced lipid droplet size when analyzed by Oil red O and H & E staining. These results demonstrated that SP-leptin is more effective than wild type leptin in normal mice in lowering their body weight and fat contents in the abdominal region, the serum, and the liver.
authors.affiliation: Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Park
authors.forename: S-B
authors.initials: SB
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Koh
authors.forename: J
authors.initials: J
authors.lastname: Kim
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D055550:Protein Stability / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D020738:Leptin; D008055:Lipids; D010455:Peptides; D011993:Recombinant Fusion Proteins