The effects of
leptin-replacement
therapy on the plasma
proteome of three unique adults with genetically based
leptin deficiency were studied longitudinally during the course of recombinant human
leptin-replacement treatment. Quantitative proteomics analysis was performed in plasma samples collected during four stages: before
leptin treatment was initiated, after 1.5 and 6 years of
leptin-replacement treatment, and after 7 weeks of temporary interruption of
leptin-replacement
therapy. Of 500
proteins reliably identified and quantitated in those four stages, about 100 were differentially abundant twofold or more in one or more stages. Synchronous dynamics of abundances of about 90
proteins was observed reflecting both short- and long-term effects of
leptin-replacement
therapy. Pathways and processes enriched with overabundant synchronous
proteins were cell adhesion, cytoskeleton remodeling, cell cycle, blood coagulation, glycolysis, and gluconeogenesis. Plausible common regulators of the above synchronous
proteins were identified using transcription regulation network analysis. The generated network included two
transcription factors (c-Myc and
androgen receptor) that are known to activate each other through a double-positive feedback loop, which may represent a potential molecular mechanism for the long-term effects of
leptin-replacement
therapy. Our findings may help to elucidate the effects of
leptin on
insulin resistance.