High glucose impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus
- Glucose intolerance,
- Hypothalamic inflammation,
- Metabolic syndrome,
How to Cite
Rabbits with high fat diet (HFD)-induced metabolic syndrome (MetS) developed hypogonadotropic hypogonadism (HH) and showed a reduced gonadotropin-releasing hormone (GnRH) immunopositivity in the hypothalamus (Filippi et al., 2009). This study investigated the relationship between MetS and hypothalamic alterations in HFD-rabbits. Gonadotropins levels decreased as a function of MetS severity, glucose intolerance, hypothalamic gene expression of glucose transporter 4 (GLUT4) and interleukin-6 (IL-6). HFD significantly induced mRNA expression and hypothalamic immunopositivity of GLUT4 and IL-6, as well as a low-grade hypothalamic inflammation (microglial activation with unchanged astroglia morphology), while reduced hypothalamic immunopositivity for KiSS-1 receptor (KiSS-1R), whose mRNA expression negatively correlated with glucose intolerance. Moreover, high glucose exposure down-regulated KiSS-1/KiSS-1R system and GnRH expression in human GnRH-secreting neuroblasts. A subset of HFD rabbits was treated with the farnesoid-X receptor agonist obeticholic acid, able to ameliorate glucose metabolism (Morelli et al., 2012). This treatment significantly increased GnRH mRNA and reduced GLUT4 and IL-6 immunopositivity. Our results suggest that HFD-induced glucose dysregulation negatively affects GnRH neuron function through an inflammatory injury at the hypothalamic level.