MON-572 - Female Sex Hormones and Obesity Regulate the Gene Expression of Glucose Receptor - Adgrl1 - in the Mouse Hypothalamus

Background: Our lab recently identified adhesion G-protein coupled receptor L1(ADGRL1) as a glucose receptor, which regulates energy balance in a sex-specific manner. Genetic deletion of hypothalamic-Adgrl1 causes obesity in male mice; however, ovariectomy in female mice is necessary to unmask the effects of the Adgrl1 in energy homeostasis. Therefore, we examined the influence of estrogen and other female sex hormones on the mouse hypothalamic Adgrl1 expression.

Methods: We used RT-qPCR to measure the Adgrl1 expression in 8 weeks old C57BL/6J female mice after ovariectomy in the presence or absence of intraperitoneal 17β-estradiol (E2, 1 mg/kg). Next, we determined the effects of human chorionic gonadotropin (HCG, 33 ug /kg, intraperitoneally), progesterone (8 mg/kg, intraperitoneally), and pregnancy on the Adgrl1 expression in different cohorts of mice. Finally, to investigate how obesity affects the Adgrl1 gene expression in female mice, we used high-fat diet (HFD), and leptin-deficient (ob/ob) mouse models. Results are presented as mean ±SEM and differences were considered statistically significant at p< 0.05.
Result: The estradiol administration decreased the Adgrl1 expression (OVX+E2, 67.6±3.3 vs ctrl, 100 ±17.9). Similarly, HCG and Progesterone downregulated the Adgrl1 expression (HCG, 29.08 ±4.6 and Progesterone, 19.89±6.5 vs ctrl, 100 ±7.5,). Although, the Adgrl1 expression was not changed by the HFD, the leptin deficient ob/ob mice had reduced hypothalamic Adgrl1 expression (HFD, 91.60 ±11.9), (Control,100 ±15.3), (OB/OB,47.80±6.1). Pregnancy at embryonic age also reduced Adgrl1 expression (59.55±4.0 vs ctrl, 100 ±7.4).

Conclusion: Our results suggest that female sex hormones including pregnancy and obesity regulate hypothalamic Adgrl1 expression. Therefore, Adgrl1 may be considered as a target for sex-specific metabolic treatments in obesity and diabetes.

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