SAT-658 Associations of Serum and CSF Kisspeptin Levels with Metabolic and Reproductive Parameters in Men

Abstract Action of kisspeptin in the central nervous system (CNS) is well known on reproductive regulation; however, its peripheral action is not well understood. Recent studies have shown that peripheral kisspeptin might be related to obesity and/or metabolic parameters in humans [1]; however, these associations are still inconclusive. This study aimed to 1) compare serum or cerebrospinal fluid (CSF) kisspeptin levels between different body mass index (BMI) groups 2) compare levels of kisspeptin between serum and CSF, and 3) determine correlations between serum or CSF kisspeptin levels with clinical, metabolic, and reproductive parameters. There were 40 male subjects who underwent an operation with lumbar puncture anesthesia. Subgroup analysis was performed to compare between the lean-normal group (n=13) which included lean and normal weight subjects, the overweight group (n=10), and the obese group (n=17) according to BMI. Blood samples were collected after at least 8-hour fasting before intravenous cannulation prior to the operation while CSF samples were obtained by lumbar puncture before administration of the spinal anesthesia. Serum kisspeptin and leptin levels were significantly higher in the obese group when compared to the lean-normal and overweight groups even after adjusted to age while CSF kisspeptin levels were comparable between different BMI groups (p<0.05 all). Serum kisspeptin levels were significantly higher than CSF kisspeptin levels (p<0.001). Serum kisspeptin was significantly positively correlated with body weight (R= 0.351), BMI (R=0.549), plasma insulin (R=0.393), and serum leptin (R=0.45) (p<0.05 all), and tended to have a positive correlation with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R=0.29, p=0.77) but was significantly negatively correlated with plasma LH (R=-0.37) (p<0.05). CSF kisspeptin was significantly positively correlated with plasma LH (R=0.452, p<0.05). These results suggest that serum kisspeptin levels were related to increased obesity, leptin, insulin, and insulin resistance while CSF kisspeptin levels were related to reproductive parameters. In summary, central kisspeptin might have a role on reproductive regulation while peripheral kisspeptin might have a role on metabolic regulation. Reference: (1) Izzi-Engbeaya, C., et al., The effects of kisspeptin on beta-cell function, serum metabolites and appetite in humans. Diabetes Obes Metab, 2018. 20(12): p. 2800–2810.