Endocrine Abstracts

JOINT536

Background: Asprosin, a novel adipokine, is the result of a profibrillin (FBN1) cleavage by furin, which also generates the mature fibrillin-1. Asprosin binds to an olfactory receptor Olfr734, influencing glucose and lipid metabolism, ovarian, and cardiovascular functions. Crossing the blood-brain barrier, it acts as an orexigenic peptide - stimulates food intake via AgRP neurons in the hypothalamus and contributing to energy homeostasis. However, its role in pituitary function remains elusive. The aim of this study was to examine asprosin/furin/Olfr734 expression in the pituitary of control (CTRL) and diet-induced obese (DIO) female mice, and in LβT-2 mouse gonadotroph cell line. Furthermore, we investigated the in vitro effects of asprosin on pituitary cell viability and proliferation.

Materials and Methods: Female C57BL/6J mice were fed a control (CTRL, n = 5) or high-fat diet (DIO, n = 5) for 12 weeks. CTRL mice were analyzed during proestrus, estrus, and diestrus, while DIO mice were studied only in estrus. Asprosin/furin/Olfr734 mRNA and protein expression were analyzed in mouse pituitary and LβT-2 cells using RT-qPCR and Western blotting, respectively. Also, serum levels of asprosin, oestradiol (E2), progesterone (P4), FSH, LH, leptin, adiponectin, triglycerides, cholesterol, and glucose were measured by ELISA and enzymatic tests. LβT-2 cells were treated with recombinant mouse asprosin at doses 1-100 nM alone or with GnRH (50 nM) for 24 h. Cell viability was measured by AlamarBlue and proliferation using BrdU assay. Statistical analyses included one-way ANOVA and Pearson’s correlation (P < 0.05).

Results: In the pituitary, asprosin/furin/Olfr734 expression varied along the estrous cycle with DIO mice exhibiting reduced expression vs CTRL. Moreover, we found that expression of asprosin and Olfr734 were negatively correlated with serum asprosin concentration and metabolic parameters, including glucose, LDL cholesterol, triglycerides, adiponectin, and leptin. Additionally, asprosin/furin/Olfr734 were detected in LβT-2 cells, where asprosin did not influence either basal or GnRH-induced viability or proliferation.

Conclusion: Our findings demonstrate that the expression of asprosin/furin/Olfr734 in the mouse pituitary is regulated by both the estrous cycle and animal metabolic status. Asprosin did not affect LβT-2 cell viability or proliferation, suggesting that its role in the pituitary may be more related to its secretory activity rather than direct cell regulation, ultimately linking metabolic changes to female reproduction. These results provide a foundation for further exploration of asprosin’s mechanisms of action in the modulation of murine gonadotrophs like gonadotropin secretion.

Funding: National Science Centre, SONATA BIS (2021/42/E/NZ4/00088).