BACKGROUND: Serum leptin variation is commonly associated with fat percentage 
(%), body mass index (BMI), and activity. In this investigation, we report 
population differences in mean leptin levels in healthy men as well as 
associations with fat % and BMI that are independent of these factors and 
reflect likely variation resulting from chronic environmental conditions.
METHODS: Serum leptin levels, fat %, and BMI were compared between lean American 
distance runners and healthy Ache Native Americans of Paraguay. Mean levels were 
compared as were the regressions between fat %, BMI, and leptin. Comparisons 
were performed between male American distance runners (n = 13, mean age 32.2 +/- 
9.2 SD) and highly active male New World indigenous population (Ache of 
Paraguay, n = 20, mean age 32.8 +/- 9.2) in order to determine whether 
significant population variation in leptin is evident in physically active 
populations living under different ecological circumstances independent of 
adiposity and BMI.
RESULTS: While the Ache were hypothesized to exhibit higher leptin due to 
significantly greater adiposity (fat %, Ache 17.9 +/- 1.8 SD; runners 9.7 +/- 
3.2, p < 0.0001), leptin levels were nonetheless significantly higher in 
American runners (Ache 1.13 ng/ml +/- 0.38 SD; runners 2.19 +/- 1.15; p < 
0.007). Significant differences in the association between leptin and fat % was 
also evident between Ache and runner men. Although fat % was significantly 
related with leptin in runners (r = 0.90, p < 0.0001) fat % was negatively 
related in Ache men (r = -0.50, p < 0.03).
CONCLUSION: These results illustrate that chronic ecological conditions in 
addition to activity are likely factors that contribute to population variation 
in leptin levels and physiology. Population variation independent of adiposity 
should be considered to be an important source of variation, especially in light 
of ethnic and population differences in the incidence and etiology of obesity, 
diabetes, and other metabolic conditions.