Blood-Brain Leptin Transport and Appetite and Reproductive Neuroendocrine Responses to Intracerebroventricular Leptin Injection in Sheep: Influence of Photoperiod

Impaired anorectic actions of leptin may be due to intrahypothalamic insensitivity and/or reduced blood-brain transport. The influence of photoperiod on leptin responses and leptin transport from blood into cerebrospinal fluid (CSF) was examined in sheep. Sheep kept on ad libitum food for 15 wk in long days (LD) had higher voluntary food intake and lower GnRH/LH output than in short days (SD). Food intake was decreased approximately 30% after intracerebroventricular (icv) (and not iv) leptin injection, but only in SD. GnRH/LH secretion was decreased after icv (but not iv) leptin in both photoperiods. Leptin concentrations in CSF were higher in LD than SD but correlated with plasma leptin only in LD. Amounts of leptin entering CSF after iv leptin injection were greater in LD than SD. In a separate experiment, plasma (but not CSF) leptin was higher in fat than thin sheep in natural summer LD and after 5 wk in SD. CSF leptin correlated with plasma leptin in LD but not SD. CSF leptin after iv leptin injection was higher in thin than fat sheep but only in LD. Endogenous CSF to plasma concentration ratios correlated negatively with plasma concentrations, indicating decreased blood-brain transport with increased leptinemia. Therefore, icv (and not iv) leptin inhibited appetite only in SD and decreased GnRH/LH output in both photoperiods, and the proportion of circulating leptin entering CSF was higher in LD and thinner animals. Photoperiod apparently modulates intrahypothalamic leptin sensitivity of appetite, but not reproductive, regulatory pathways, whereas photoperiod and leptinemia influence leptin blood-brain transport.