EFFECT OF FASTING, REFEEDING, AND DIETARY-FAT RESTRICTION ON PLASMA LEPTIN LEVELS

The factors responsible for the variability in plasma leptin levels ob served among individuals with similar body compositions remain unclear . To examine the impact of dietary variables, we compared the changes in leptin levels induced by fasting and dietary fat restriction with t he expected decrease following a significant loss in adipose mass. A 2 1.4+/-3.7% weight loss led to a 76.3+/-8.1% decrease in mean plasma le ptin level (25.2+/-9.3 to 6.1+/-3.4 ng/mL, P=0.0001) in a group of 9 o bese males. Despite a weight loss of only 2.6+/-0.8%, mean plasma lept in levels fell by 61.9+/-25.2% (8.5+/-4.5 to 2.4+/-0.5 ng/mL, P <0.01) in 7 nonobese females subjected to 3 days of fasting. Leptin levels i n fasted subjects returned to baseline within 12 h of refeeding. Indiv idual high- and low-fat meals given to 19 subjects after an overnight fast had no effect on plasma leptin levels. Reduction in dietary fat c ontent from 37-10% of total calories for 7 weeks was also without effe ct on plasma leptin levels in these subjects. We conclude that plasma leptin levels primarily reflect total adipose mass, rather than meal c onsumption or dietary energy source, but that the reduction in leptin levels with ongoing fasting is disproportionate to the reduction in ad ipose mass. The ability of fasting to deactivate this presumed physiol ogical satiety system may have been advantageous in environments chara cterized by rapid changes in food availability.