We studied the heterozygous relatives of our leptin deficient subjects (Farooqi et al., 2001). Serum leptin levels in the heterozygous subjects were found to be significantly lower than expected for % body fat and they had a higher prevalence of obesity than seen in a control population of similar age, sex and ethnicity (Farooqi et al., 2001). Additionally, percentage body fat was higher than predicted from their height and weight in the heterozygous subjects compared to control subjects of the same ethnicity. These findings closely parallel those in heterozygous ob- and db/-mice (Chung et al., 1998). These data provide further support for the possibility that leptin can produce a graded response in terms of body composition across a broad range of plasma concentrations.
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