Oversecretion of leptin in normal mice results in a lean phenotype characterized by drastic reductions in their white fat

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A mouse with normal levels of leptin has plenty of white fat (left), whereas a transgenic mouse (right) overexpresing leptin has very little fat. This picture demonstrates that overexpression of leptin can reduce the adipose mass when the genetic background does not hinder the activity of excess leptin. Unfortunately, in most animal models of obesity and in obese individuals, the excess leptin produced by the increased fat mass cannot perform its adipose mass reducing function due to a block somewhere in the leptin pathway.

A mutation causing leptin deficiency results in an obese state. However, the same mutation results in two different phenotypes depending on the genetic background on which the mutation segregates

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Leptin deficiency results in a severe obese state and sterility when the mutation is on the C57BL/6J genetic background as shown in the obese mouse with the black coat color. However, when the mutation segregates on the Balb/cJ genetic background as shown in the white coat color mouse, the obesity is alleviated and fertility ensues. This picture shows how the genetic background influences the expression and the severity of obesity as caused by leptin deficiency.