L-carnitine ameliorates decidualization in high-fat diet-induced obese rats and human endometrial stromal cells treated with palmitic acid

RESEARCH QUESTION: Does L-carnitine ameliorate impairment of endometrial decidualization in high-fat diet-induced obese rats and human endometrial stromal cells (HESC) treated with palmitic acid-treated? DESIGN: Obese female rats (n = 10 per group; 5 weeks old at commencement of dietary intervention) induced by a high-fat diet for 8 weeks were administered L-carnitine at doses of 135, 400 and 1200 mg/kg/day via oral gavage for 5 weeks, with metformin serving as the control. After mating, uterine specimens were collected on gestational day 7 and analysed by various techniques, including haematoxylin and eosin staining, and Western blotting. Additionally, palmitic acid was used to induce lipid accumulation in immortalized HESC, followed by treatment with L-carnitine to investigate its effects on decidualization processes. RESULTS: Compared with metformin, the administration of L-carnitine (400 mg/kg/day) restored the number of embryo implantation sites and decidualization in vivo. L-carnitine was found to increase the expression of sirtuin 1 (SIRT1) and Forkhead box class O 1 (FOXO1), while simultaneously decreasing expression of acetyl-FOXO1. In vitro, L-carnitine reversed the palmitic acid-induced suppression of decidualization markers and restored mitochondrial polarization. Notably, L-carnitine treatment restored SIRT1/FOXO1 signalling pathways and enhanced the expression of the progesterone receptor in vivo and in vitro. CONCLUSIONS: L-carnitine ameliorates impaired endometrial decidualization in rats fed a high-fat diet and HESC treated with palmitic acid via the SIRT1/FOXO1/progesterone receptor pathway.