The Effect of Troxerutin on Apelin-13 and Its Receptor Gene Expression in Ovarian of Pregnant Rats Fed a High-Fat Diet

Abstract

Background & Objective: Apelin is a newly discovered member of adipocytokines that acts as an endogenous ligand for the G-coupled receptor for the protein orphan (APJ). This study aimed at investigating the beneficial effect of troxerutin (TRO) on apelin-13 and its receptor mRNA expression in the ovary of high-fat diet (HFD) fed rats.
 Materials & Methods: 40 three-week old female Wistar rats received control diet (CD) or HFD for 8 weeks. After mating, pregnant animals were divided into 4 subgroups: CD, CD +TRO, HFD, and HFD + TRO. Respective diets continued to the end of lactation. CD +TRO and HFD +TRO groups received troxerutin (150 mg/kg/day, P.O.) during pregnancy. After weaning offspring, animals in the maternal group were sacrificed. Then blood samples and ovarian tissue samples were collected for further evaluation.
 Results: The results indicated that HFD significantly increased serum apelin-13 in HFD dams, which was reversed by TRO treatment. Also, analysis showed that ovarian mRNA expression of the apelin receptor markedly down-regulated in the HFD group compared to control groups. It was also revealed that treatment with troxerutin in the HFD group could significantly increase apelin receptor mRNA expression in comparison with the both CD and HFD groups.
 Conclusion: Troxerutin treatment in obese pregnant mothers can affect the function of the reproductive system by modulating the serum apelin 13 and the expression of its receptor gene.

The role of apelinergic system in metabolism and reproductive system in normal and pathological conditions: an overview

“…functions in normal and pathological conditions in humans and animal models. Int J Mol Sci (2019) 20 (18):4431. doi: 10.3390/ijms20184431…”

“…Maternal nutrition during pregnancy can lead to growth abnormalities and reproductive dysfunctions (32). Our previous study revealed that maternal HFD during pregnancy and lactation markedly decreased the number of primary, secondary, and graafian follicles, while increasing the number of atretic follicles in their offspring (18). HFD has also been shown to increase atretic follicles through upregulation of ovarian cell cycle inhibitors, expansion of granulosa cells (Gc) apoptosis (33), or modifications of the expression of genes engaged in growth, development, and apoptosis of follicles in the ovary (34).…”

“…In this regard, a study showed that HFD feeding during lactation increases the concentration of apelin in breast milk, possibly by upregulation of apelin expression in myoepithelial cells in the mammary gland (126). Long-term HFD consumption by inducing insulin resistance and hyperinsulinemia increase apelin secretion from adipose tissue (123,128,129). 9 Apelin in metabolic disorders…”

“…Maternal obesity and HFD also have adverse effects on the reproductive systems of offspring ( 18 ). Epidemiological studies in recent decades show that maternal nutrition during pregnancy has important effects on the offspring’s fertility ( 31 ).…”

“…According to previous studies, obesity and T2DM by inducing insulin resistance increase apelin levels ( 17 ). Moreover, previous studies indicated that the serum levels of apelin and its receptor gene expression can be influenced by diet ( 18 , 19 ). Apelin expression is also influenced by nutritional status and its plasma levels decrease with fasting and increase with re-feeding ( 16 ).…”