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| RECOMBINANT OB PROTEIN REDUCES FEEDING AND BODY-WEIGHT IN THE OB/OB MOUSE |
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| Author(s): WEIGLE DS, BUKOWSKI TR, FOSTER DC, HOLDERMAN S, KRAMER JM, LASSER G, LOFTONDAY CE, PRUNKARD DE, RAYMOND C, KUIJPER JL |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 96 Issue: 4 Pages: 2065-2070 Published: OCT 1995 |
| Times Cited: 347 References: 25 |
| Abstract: To determine whether the product of the recently cloned ob gene functions as an adipose-related satiety factor, recombinant murine ob protein was administered intraperitoneally to ob/ob mice. Monomeric ob protein given as single morning injections to groups of three animals at seven doses ranging from 5 to 100 mu g reduced 24-h chow consumption in a dose-dependent manner from values of 81+/-6.8% of control (10-mu g dose, P = 0.04) to 29+/-7.7% of control (100-mu g dose, P < 0.0001). Daily injections of 80 mu g of ob protein into six ob/ob mice for 2 wk led to an 11+/-1.6% decrease in body weight (P = 0.0009) and suppressed feeding to 26+/-4.9% of baseline (P < 0.0001), with significant reduction of serum insulin and glucose levels. The effect of recombinant ob protein on feeding was not augmented by cofactors secreted by adipose tissue, nor did exposure of adipose tissue to ob protein affect intracellular ob mRNA levels. Posttranslational modification of ob protein was not required for activity; however, addition of a hexahistidine tag to the amino terminus of the mature ob protein resulted in prolonged suppression of feeding after injection into ob/ob mice. These results demonstrate a direct effect of the ob protein to suppress feeding in the ob/ob mouse and suggest that this molecule plays a critical role in regulating total body fat content. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WASHINGTON, SCH MED, DEPT MED, SEATTLE, WA 98195 USA
2. ZYMOGENET CORP, SEATTLE, WA 98102 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: RY954 |
| ISSN: 0021-9738 |
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