Laboratory of Molecular Genetics
Weight-reducing effects of the plasma protein encoded by the obesegene
Halaas JL. Gajiwala KS. Maffei M. Cohen SL. Chait BT. RabinowitzD. Lallone RL. Burley SK. Friedman JM.
The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouseor human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injectionsof wild-type mice twice daily with the mouse protein resultedin a sustained 12 percent weight loss, decreased food intake,and a reduction of body fat from 12.2 to 0.7 percent. These datasuggest that the OB protein serves an endocrine function to regulatebody fat stores.