WEIGHT-REDUCING EFFECTS OF THE PLASMA-PROTEIN ENCODED BY THE OBESE GENE

The gene product of the ob locus is important in the regulation of bod y weight. The ob product was shown to be present as a 16-kilodalton pr otein in mouse and human plasma but was undetectable in plasma from C5 7BL/6J ob/ob mice. Plasma levels of this protein were increased in dia betic (db) mice, a mutant thought to be resistant to the effects of ab . Daily intraperitoneal injections of either mouse or human recombinan t 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 d b/db mice. The protein reduced food intake and increased energy expend iture in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreas ed food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.