Adiponectin sEV applications on metabolic diseases
Stable, multimerised, native APN on sEVs for metabolic balance and health
Using the EVENGI platform, Ciloa has succeeded in producing stable, multimerised, native adiponectin (APN) by targeting it to the surface of small extracellular vesicles (sEVs).
Treatments using the resulting APN-sEVs have been shown to impact lipogenesis, gluconeogenesis and fatty acid oxidation. Such results can have dramatic implications on therapies of all metabolic diseases.
Adiponectin signaling pathways
From the scientific literature, it appears that adiponectin (APN) exerts its functional effects via two transmembrane receptors (AdipoR1 and AdipoR2) and a GPI-anchored receptor (T-cadherin). Metabolism regulation by APN can be explained by its interactions with these receptors, which act as gateways to a network of signalling pathways that interact with the insulin pathway and glucose uptake.
The obese/diabetes mouse model with liver impairment that was treated with APN-sEVs emphasises the aforementioned reports.
APN-sEVs indeed act on several signalling pathways, which are shown in orange in the figure. APN-sEVs reduce the levels of mRNA coding for proteins involved in lipogenesis, gluconeogenesis, and fatty acid oxidation. It is important to note that GLP-1RA has no influence on any of the mRNAs linked to these pathways. In addition, APN-sEVs reduce the levels of mRNA involved in inflammation. Therefore, APN-sEVs and GLP-1RA act on different but complementary signalling pathways, which explain the all beneficial effects of APN-sEVs treatment and APN-sEVs and GLP-1RA co-treatment against obesity, type 2 diabetes and MAFLD, as observed in the DIO/NASH mouse model.
