Genes induce human obesity.

In recent years, studies of abnormally hefty rodents have revealed several genetic mutations that induce obesity. Scientists have now found similar mutations in people, although they stress that such genetic flaws are rare.

In the June 26 Nature, Stephen O'Rahilly of the University of Cambridge in England and his colleagues describe an 8-year-old girl and a 2-year-old boy, cousins and both dangerously obese, who have mutations in the gene for the hormone leptin. Leptin, secreted by fat cells, is thought to govern body weight by sending signals to the brain (SN: 7/29/95, p. 68).

Since finding that mice with mutations in their leptin gene become obese, scientists had unsuccessfully searched thousands of people for similar mutations.

In the July Nature Genetics, O'Rahilly's group describes a second obesity-inducing human mutation. They analyzed a woman who had been dangerously obese during her childhood but who has since controlled her weight through dieting. She has a mutant gene for prohormone convertase 1, an enzyme that activates certain proteins, including insulin, as the final step in their production. A similar enzyme is mutated in some obese mice, though how such enzymes influence body weight remains unclear (SN: 6/3/95, p. 341).

"These observations are important not because the etiology of most human obesity has been elucidated--it has not--but because they vindicate an approach to this complex phenotype that emphasizes biology over `will power' and regards body weight as the result of complex interactions between genes and environment rather than a psychological aberration of free will," comments Rudolph L. Leibel of Rockefeller University in New York in the same issue of Nature Genetics.