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Submitted on May 2, 2006
Accepted on June 13, 2006
Obesity & Metabolic Health Division, Rowett Research Institute, Aberdeen Centre for Energy Regulation & Obesity, Bucksburn, Aberdeen AB21 9SB, Scotland, UK
* To whom correspondence should be addressed. E-mail: cla{at}rowett.ac.uk.
Impaired anorectic actions of leptin may be due to intra-hypothalamic 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 weeks in long days (LD) had higher voluntary food intake and lower GnRH/LH output than in short days (SD). Food intake was decreased 
30% after 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 weeks in SD. CSF leptin correlated with plasma leptin in LD but not in SD. CSF leptin after iv leptin injection was higher in thin than fat sheep, but only in LD. Endogenous CSF: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 in thinner animals. Photoperiod apparently modulates intra-hypothalamic leptin sensitivity of appetite, but not reproductive, regulatory pathways while photoperiod and leptinemia influence leptin blood-brain transport.
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