Endocrine Abstracts

JOINT122

Omentin-1 has significant implications for metabolism and insulin sensitivity, especially in obesity, metabolic syndrome, and inflammatory diseases. Also, expression of omentin-1 has been observed in reproductive cells including the ovary, placenta, and anterior pituitary (AP). Moreover, omentin-1 regulates steroid hormone secretion through the upregulation of steroidogenesis-related proteins. This highlights its significant role in the regulation of female reproductive hormones. The objective of the present study is to examine the in vitro effects of omentin-1 on the global proteome and its role in the regulation of tropic hormone levels and signaling pathways in porcine AP cells. To investigate this, AP cells were isolated from Large White (LW; normal body weight) and Meishan pigs (MS; genetically obese) during the mid-luteal phase of estrous. We conducted liquid chromatography-tandem mass spectrometry with tandem mass tag labeling following a 24-hour treatment with omentin-1 (50 ng/mL). Functional analyses were performed to investigate dose-dependent of omentin-1 (10, 50, 100 ng/mL) alone and in combination with GnRH (100 ng/mL), CRH (1000 nM), TRH (1000 nM), and GHRH (100 nM) on the expression and secretion of LH, FSH, ACTH, TSH, PRL, GH, and their respective hypothalamic receptors in AP cells (using RT-qPCR and ELISA). We also explored the role of OMNT1 on gonadotropins secretion via extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase C, and insulin receptor signaling pathways (using ELISA). Statistical analysis used two-way ANOVA, and Tukey’s post-hoc test (n = 4 at least). Proteomic analysis identified ~7,000 proteins, 34 differentially expressed in LW pigs, and 198 in MS, (cutoff 1.2-fold, P < 0.05). Bioinformatics using the DAVID, Panther, and Reactome platforms highlighted the involvement of omentin-1 in gonadotropin regulation, insulin receptor recycling, immune response, and transport to the Golgi and subsequent modification, homeostasis, and metabolism. In MS, proteins upregulated included LHβ, VDAC3, and cathepsin D, while SARM1 and ERK1/2 were downregulated. In LW, RRAGD was downregulated, and in both breeds, SIX1 was downregulated. Functional experiments have revealed that omentin-1 plays a modulatory role in the expression and secretion of tropic hormones. Additionally, it is involved in key signaling pathways, including ERK1/2, and protein kinase C suggesting its significant impact on cellular signaling and endocrine regulation in AP cells. The description of the molecular mechanism of omentin-1 action creates new opportunities for research into targeted therapy and improvement of efficiency of livestock production through modulation of hormonal functions.

Funding: National Science Centre, Poland (2020/37/B/NZ9/01154).