Adaptive response of hepatic acetyl-CoA carboxylase to dietary alterations in genetically obese mice and their lean controls |
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Authors: | Michael E Maragoudakis Hilda Hankin Helen Kalinsky |
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Institution: | Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Ardsley, N.Y. 10502 U.S.A. |
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Abstract: | 1. 1. Genetically obese mice (C5 7BL/6J-ob/ob, Jackson Laboratories) have much higher levels of hepatic acetyl-CoA carboxylase activity than their lean siblings, under a variety of nutritional states. However, when these mice are fasted for 48 h and then refed a fat-free diet for 48 h, the activity of this enzyme in the lean group shows about a 9-fold increase over the measured under normal dietary conditions, while obese mice show only 1 2-fold increase. The acetyl-CoA carboxylase activity observed under the dietary conditions is thus comparable in both lean and obese animals. Oil feeding or fasting for 48 h markedly depresses the activity of this enzyme in both groups and seems to be an effective means of reducing acetyl-CoA carboxylase activity in the obese mice, particularly, to far below the values found under normal dietary conditions. 2. 2. Both acetyl-CoA carboxylase and fatty acid synthetase purified from livers of obese and lean mice show comparable specific activities and no demonstrable differences with respect to their kinetic properties. Acetyl-CoA carboxylase from the two sources is also identical with respect to sensitivity to reagents and other inhibitors (such as malonyl-CoA, palmitoyl-CoA, etc.), to heat inactivation and in its sedimentation properties. These results suggest quantitative differences rather than differences in the catalytic and regulatory properties of the obese and lean enzymes. |
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Keywords: | TPIA sodium 2-methyl-2-[p-(1 2 3 4-tetrahydro-1naphthyl)-phenoxy]-propionate |
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