Diurnal variation in circulating leptin is dependent on gender, food intake and circulating insulin in mice

Leptin is an adipocyte hormone involved in the regulation of energy homeostasis. Its circulating levels show a diurnal rhythm with a nocturnal peak. We examined the influences of gender, feeding state, and plasma insulin and glucose on the diurnal rhythm in normal mice. Plasma was sampled at 4-h interval for 24 h in female (n=80) and male (n=80) mice, which were freely fed or fasted. In both genders, plasma leptin displayed a diurnal rhythm with a nadir at 8 or 10 AM and a nocturnal peak at 10 PM to 2 AM. The nocturnal increase in leptin was higher in females (+160+/-18%) than in males (61+/- 16%; P<0.001), completely abolished by fasting, and correlated significantly to the diurnal variation in plasma insulin both in females (r=0.44, P=0.003) and males (r=0.46, P<0.001). Baseline plasma leptin in non-fasted animals were not different between the genders, whereas during fasting, the reduction in leptin was more pronounced in males than in females, resulting in a higher plasma leptin after fasting in females. Plasma insulin was higher in males under non-fasted conditions (P=0.003), but not significantly different between genders in fasted animals. In conclusion, plasma leptin displays a nocturnal increase in mice, which is more pronounced in female mice than in male mice, is completely abolished by fasting and correlates to the diurnal variation in circulating insulin. It is suggested that the nocturnal rise in leptin shows gender dependency and is caused by the increase in plasma insulin caused by food intake.