ROLE OF LEPTIN IN THE NEUROENDOCRINE RESPONSE TO FASTING

A TOTAL deficiency in or resistance to the protein leptin causes sever e obesity(1-4). As leptin levels rise with increasing adiposity in rod ents(5) and man(6,7), it is proposed to act as a negative feedback 'ad ipostatic signal' to brain centres controlling energy homeostasis, lim iting obesity in times of nutritional abundance(1,3). Starvation is al so a threat to homeostasis that triggers adaptive responses(8-12), but whether leptin plays a role in the physiology of starvation is unknow n. Leptin concentration falls during starvation(13) and totally leptin -deficient ob/ob mice have neuroendocrine abnormalities similar to tho se of starvation(14), suggesting that this may be the case. Here we sh ow that preventing the starvation-induced fall in leptin with exogenou s leptin substantially blunts the changes in gonadal, adrenal and thyr oid axes in male mice, and prevents the starvation-induced delay in ov ulation in female mice. In contrast, leptin repletion during this peri od of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system d uring starvation could be the main physiological role of leptin.