L-carnitine increases cell proliferation and amino acid transporter expression via the activation of insulin-like growth factor I signaling pathway in rat trophoblast cells

Shihai Zhang; Zhihui Wu; Jinghui Heng; Min Tian; Jiaming Chen; Fang Chen; Wutai Guan

doi:10.1002/fsn3.1607

L-carnitine increases cell proliferation and amino acid transporter expression via the activation of insulin-like growth factor I signaling pathway in rat trophoblast cells

Food Sci Nutr. 2020 Apr 28;8(7):3298-3307. doi: 10.1002/fsn3.1607. eCollection 2020 Jul.

Authors

Shihai Zhang^{1

2}, Zhihui Wu^{1

2}, Jinghui Heng^{1

2}, Min Tian^{1

2}, Jiaming Chen^{1

2}, Fang Chen^{1

2}, Wutai Guan^{1

2}

Affiliations

¹ Guangdong Province Key Laboratory of Animal Nutrition Control College of Animal Science South China Agricultural University Guangzhou China.
² College of Animal Science and National Engineering Research Center for Breeding Swine Industry South China Agricultural University Guangzhou China.

Abstract

Early embryo implantation and development is primarily determined by the homeostasis between cellular apoptosis and proliferation as well as placental nutrient transporters. Recent studies showed that L-carnitine enhances female reproductive performance. However, the potential function of L-carnitine on placenta is largely unknown. In our study, primary rat trophoblast cells were separated and cultured for 12 hr in medium containing various concentrations of L-carnitine (0, 1, 10, and 50 mM). Placenta trophoblast cells treated with 50 mM L-carnitine increased the proportion of cells in S phase of the cell cycle (p < .05). In addition, live cell percentage was increased when treated with either 10 mM or 50 mM L-carnitine, which was accompanied with decreased necrotic cells, late apoptotic cells, and early apoptotic cells (p < .05). Compared with the control treatment, the mRNA expression of insulin-like growth factor I (IGF-1) and insulin-like growth factor I receptor (IGF-1R) was higher in rat placenta trophoblasts treated with either 10 mM or 50 mM L-carnitine (p < .05). Similarly, sodium-dependent neutral amino acid transporter (SNAT)-1 and SNAT2 were up-regulated in both mRNA and protein levels when trophoblast cells were treated with 50 mM L-carnitine (p < .05). Inhibiting downstream targets (Akt or ERK signaling pathways) of IGF-1 signaling pathway partially blocked the effect the L-carnitine-induced increase in protein abundances of SNAT1 and SNAT2. Collectively, our data showed protective role of L-carnitine on placenta trophoblast cells through the involvement of IGF-1 signaling pathway.

Keywords: IGF‐1 signaling; L‐carnitine; nutrient transporter; reproduction.