Leptin levels in lines of mice developed by long-term divergent selection on fat content

The mouse lines were developed by long-term selection for fatness, after wh ich the fat line (F) had about a 5-fold (23% vs 4%) higher fat percentage t han the lean (L) line at 14 weeks; but the lines differed little in fat-fre e body weight. To assess the contribution of genetic changes in leptin horm one level to the selection response, plasma leptin levels were assayed in t hese lines in generation 60 and in an unselected control (C) from the same base population. With access to food prior to assay, the F, C and L lines h ad 16.5, 0.91 and 0.26 ng/ml leptin, respectively. In fasted animals these levels were much lower: 2.98, 0.171 and 0.0087 ng/ml, respectively. Thus th e leptin levels differ greatly between the lines, with the fattest mice sho wing the highest level: almost 20 times higher than the control and 60-300 times higher than the L line. These correlated selection effects are an ord er of magnitude greater than the direct selection response, and believed to be much larger than seen for any hormonal or other trait. Correlations bet ween leptin level and fat amount were high (over 0.86) in fed or fasted ani mals of the F line, indicative of leptin resistance.