Effects of high-fat diet and treadmill running on the hypothalamic Kiss-1–GPR54 signaling pathway in male growing rats

Background: Kiss-1 neuron, one of the metabolic sensors in the hypothalamus, is necessary for puberty initiation. It acts through G protein-coupled receptor, known as GPR54. In this study, the mechanism of the hypothalamic Kiss-1–GPR54 signaling pathway in a high-fat diet and exercise was investigated in growing male rats. Methods: A total of 135 3-week-old male weaned rats were kept on a high-fat diet (HFD) and exercise (60–70% V ˙ O , 1 h/day, 5 days/week). They were randomly divided, as follows: control group (C); normal diet + exercise group (CE); HFD group (H); and HFD + exercise group (HE). Hypothalamus, testis, and serum samples of each group were collected on postnatal day (PND) 21 (early childhood), 43 (puberty), and 56 (maturity). Immunofluorescence, quantitative real-time PCR, hematoxylin and eosin staining, and chemiluminescent immunoassays were used in the study. ANOVA was used to analyze the effects of age (PNDs 21, 43, and 56), exercise (exercise and sedentariness), and diet (high-fat and normal) on the biological indices of rats. Results: mRNA and protein expression of Kiss-1 and GPR54 in the hypothalamus gradually increased along with growth and peaked at PND 43, while those in serum testosterone increased and peaked at PND 56. The high-fat diet increased the expression of the Kiss-1–GPR54 system in the hypothalamus, whereas the serum testosterone decreased during different stages of growth. Exercise decreased the expression of Kiss-1 at PND 56 and increased it at PND 43. Meanwhile, it decreased testosterone and the deposition of lipid droplets in the testis at all ages of development. Conclusions: The expression of Kiss-1–GPR54 in male rats showed fluctuating changes during growth and development. The high-fat diet was able to upregulate the expression of the Kiss-1–GPR54 system in the hypothalamus. The exercise was able to correct the adverse effect of the high-fat diet on the Kiss-1–GPR54 signaling pathway in the hypothalamus and the function of the hypothalamic-pituitary–gonadal (HPG) axis, but had age-specific effects on the male rats’ development.