Appetite Control: Does leptin lighten the problem of obesity?

Events of the past twelve months have had an explosive impact on the field of obesity research. This wave of excitement was triggered by a momentous announcement from Zhang et al. [1] in December 1994. The authors reported that they had identified the gene responsible for obesity in one of the most intensively studied genetic rodent models of the disorder, the ob/ob mouse, homozygous for a mutant form of the obese (ob) gene. It turned out that the normal ob gene is expressed only in fat tissue; it encodes a protein, OB, of molecular weight -18 kDa, which contains an -2 kDa cleavable leader sequence, indicating that it is a secreted product. The ob gene product appears to be highly conserved among vertebrates, the mouse and human homologues being 84 % identical at the amino-acid level. The mutation in C57BL/6J strain ob/ob mice introduces a stop codon into the ob mRNA, causing failure to produce normal OB protein and, interestingly, a 20-fold overexpression of the useless mRNA in white fat. A second mutation is found in ob2J/ob2J mice; in this case, the mutation occurs in the 5' region of the ob gene and prevents the synthesis of any ob mRNA [1].