LEPTIN LEVELS DO NOT CHANGE ACUTELY WITH FOOD ADMINISTRATION IN NORMAL OR OBESE SUBJECTS, BUT ARE NEGATIVELY CORRELATED WITH PITUITARY-ADRENAL ACTIVITY

BACKGROUND Leptin is a peptide secreted by white adipose tissue which has been shown to have a major influence on body weight regulation, wh ile animal studies have revealed widespread interconnections between l eptin and other endocrine systems, especially with insulin. However, i ts acute regulation has been little studied in the human. We have ther efore investigated the effect of a 1000 kcal meal and fasting on the l evels of leptin, insulin and cortisol, in both normal and obese subjec ts. SUBJECTS AND DESIGN We have studied the effect of food and fasting on circulating leptin levels in 20 subjects of normal body mass index (BMI range 18-25) and in a group of 12 moderately-severely obese subj ects (BMI range 34-61). We also studied the effect of food and fastina in a patient both before and after the successful removal of a pancre atic insulinoma as a model of excess insulin secretion. RESULTS Mean l eptin levels were significantly higher in the obese than in the lean g roup (42.7 +/- 3.41 vs 5.35 +/- 1.55 mu g/l, mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after food did not show any acute changes in circulating leptin levels. On the fa sting day we observed a small but significant fall in circulating lept in levels in the last 4 hours of a 20-hour fast in our subjects as a g roup (92 +/- 0.03% of basal, P = 0.03); however, in the lean subjects the fall was greater (88 +/- 0.04% of basal, P = 0.02) than in the obe se, where it did not reach statistical significance (96 +/- 0.05% of b asal). Pre-meal and peak insulin levels showed a positive correlation with circulating mean leptin levels (r = 0.65; P < 0.001 and r = +0.78 ; P < 0.001, respectively) in all subjects, while pre-meal and peak se rum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of BMI in the obese subjects. In the patient with the insulinoma the markedly elevated insulin and leptin levels measured be fore the operation returned to normal after removal of the tumour, in accord with reports of experimental animal data that long-term insulin excess per se is associated with increased circulating leptin concent rations. CONCLUSION Leptin is a robust indicator of BMI and insulin le vels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin leve ls in lean subjects than in obese subjects. Circulating leptin is inve rsely correlated with the activity of the hypothalamo-pituitary-adrena l axis: whether this is a direct influence of leptin on hypothalamo-pi tuitary-adrenal activity, or whether both are indirect indicators of b ody fat stores, requires further investigation.