Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene

JL Halaas, KS Gajiwala, M Maffei, SL Cohen, BT Chait… - Science, 1995 - science.org
JL Halaas, KS Gajiwala, M Maffei, SL Cohen, BT Chait, D Rabinowitz, RL Lallone, SK Burley
Science, 1995science.org
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 mouse or human recombinant OB protein reduced
the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent …
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 mouse or 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. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased 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.
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