Leptin increases lipid storage in Sertoli cells: Signaling pathways and cellular mechanisms involved

Abstract

Leptin is an adipokine with a role in male reproductive function. Sertoli cells (SCs) express leptin receptors, but leptin effects on SCs’ functions have been scarcely researched. SCs support germ cell development by providing various compounds, including transferrin and ketone bodies. Additionally, SC oxidize fatty acids (FAs) as their primary energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as a crucial energy reserve within SCs. In the present study, we investigated whether leptin regulates the secretion and lipid storage in SCs and identified the potential signaling pathways involved. SC cultures were obtained from 20 day-old rats. The results show that leptin does not modify transferrin or 3-hydroxybutyrate secretion. However, it increases LD content and TAG levels in SCs. Leptin also augments the mRNA levels of FA transporter FAT/CD36, glycerol-3- phosphate-acyltransferase 3, and perilipin 1. We then explored the activation and the involvement of JAK/STAT3, PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. Leptin treatment increases phosphorylated STAT3, AKT, and p70S6K levels. Also, leptin augments PPARɣ mRNA levels. In addition, we observed that Wortmannin (PI3K inhibitor), Rapamycin (mTORC1 inhibitor), and T0070907 (PPARɣ antagonist) decrease leptin stimulated LD content, but Stattic (STAT3 inhibitor) has no effect. These results suggest that leptin regulates LD content through the activation of PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. This study reveals that leptin increases lipid storage in SCs, a role that may help meet the seminiferous tubules´ demand for FAs.