Asprosin activates multiple placental pathways in vitro: Evidence for potential involvement in angiogenesis, fatty acid metabolism and the mTOR, NOTCH and WNT signalling pathways.

Abstract

Asprosin is glucogenic adipokine that exerts a wide repertoire of actions, including the regulation of appetite, insulin resistance and cell proliferation. At present, little is known about the actions of asprosin in the human placenta. The present study investigated the effects of asprosin on the transcriptome of the BeWo and JEG‑3 placental cell lines, and assessed the expression of FBN1/Furin and asprosin's candidate receptors in healthy placentas when compared against placentas from pregnancies where the carrier had gestational diabetes mellitus (GDM). A number of methods, including tissue culture, clinical sample collection, RNA extraction, RNA sequencing, reverse transcription‑quantitative PCR and gene enrichment analyses were used in the present study. RNA sequencing revealed that asprosin induced cell specific differential expression for 51 genes in BeWo cells, and 204 in JEG‑3 cells, with nine common differentially expressed genes in both in vitro models including SLCA1 and HK2. Specific pathways involved in angiogenesis, fatty acid metabolism and mTOR/NOTCH/WNT/p53 signalling were also enriched. Only TLR4 was significantly downregulated in GDM placentas when compared with controls. The present study provides novel insight into the actions of asprosin in two well‑established in vitro placental (trophoblast) models, identifying key genes and signalling pathways. A common theme identified from these findings is that of glucose homeostasis, in accordance with the role of this adipokine.