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These results indicate that leptin behaves as if it backache is monitoring total body fat content independent of regional fat distribution, insulin level, presence of diabetes, or presence of the chromosomal disorder that results in the Prader-Willi syndrome. Leptin is, therefore, an ideal candidate for the lipostatic factor postulated by Kennedy (22) to play a dominant role in regulating body composition. The positive exponential relationship of plasma leptin level to body fat content should result in the delivery of an increasingly strong satiety and thermogenic signal to the CNS as backache obesity backache becomes more severe (1, 2, 3, 4). The fact that obesity can coexist with a high leptin level has been interpreted to indicate the presence of leptin resistance with increasing body fat content (5). An alternative explanation could be that a totally unrelated defect leads to a progressive gain in adipose tissue that is limited only when the plasma leptin level becomes high enough to deliver a supernormal counterregulatory signal to a normally leptin-sensitive CNS.
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