Wen Zhongl et al, Adipose specific aptamer adipo-8 recognizes and interacts with APMAP to ameliorates fat deposition in vitro and in vivo, Life Sciences. 117609. https://doi.org/10.1016/j.lfs.2020.117609
To identify the target of an adipose specific aptamer adipo-8, predict the potential interaction between adipo-8 and its target, and investigate lipid-lowering effect of adipo-8 in vitro and in vivo.
Distinct membranous protein of 3T3-L1 adipocyte pulled-down by adipo-8 was mass-spectrometry analyzed as target candidate(s), and affinity of adipo-8 to target protein-silent adipocyte was detected to validate it. Interaction between adipo-8 and target was predicted by bioinformatic analysis, further confirmed by aptamer truncation and competitive binding assay. To investigate lipid-lowering effect of adipo-8 and mechanism behind, 250 nmol/L adipo-8 or library was incubated with 3T3-L1 adipocyte or target-protein-silent adipocyte for 24 h, and 0.01 μg/g/day adipo-8 or library was administrated to high-fat-fed male mice for 21 days.
APMAP (Adipocyte Plasma Membrane Associated Protein) was identified as adipo-8 target, and adipo-8 affinity to adipocytes was in proportional to APMAP expression. Docking model between the stem-loop structure of adipo-8 and APMAP were predicted that adipo-8 was likely to interact with APMAP at its amino-acid 275–411 sequence. Moreover, adipo-8 could ameliorate fat deposition through interaction with APMAP in vitro, and administration of adipo-8 in high-fat-diet fed mice resulted in body weight loss and blood triglyceride decrease without liver or renal dysfunction.
Adipo-8 could recognize APMAP specifically and interact with its targets to ameliorate fat deposition in vitro and in vivo. Aptamer adipo-8 has potential to act as an effective and safe targeted drug for obesity and obesity related diseases.