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Rapid Publications

Elevated Free Fatty Acids Induce Uncoupling Protein 3 Expression in Muscle: A Potential Explanation for the Effect of Fasting

  1. David S Weigle,
  2. Leah E Selfridge,
  3. Michael W Schwartz,
  4. Randy J Seeley,
  5. David E Cummings,
  6. Peter J Havel,
  7. Joseph L Kuijper and
  8. Hector BeltrandelRio
  1. Departments of Medicine, Harborview Medical Center and Puget Sound Veterans Administration Health Care System Seattle, Washington
  2. Psychology, University of Washington, Harborview Medical Center and Puget Sound Veterans Administration Health Care System Seattle, Washington
  3. ZymoGenetics Corporation Seattle, Washington
  4. Department of Nutrition, University of California Davis, California
  1. Address correspondence and reprint requests to Dr. David S. Weigle, Box 359757, Harborview Medical Center, 325 Ninth Ave., Seattle, WA 98104. Email: weigles{at}zgi.com
Diabetes 1998 Feb; 47(2): 298-302. https://doi.org/10.2337/diab.47.2.298
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Abstract

The newly described uncoupling protein 3 (UCP3) may make an important contribution to thermogenesis in humans because of its high level of expression in skeletal muscle. Contrary to expectations, fasting, a condition that reduces resting energy expenditure, has been reported to increase UCP3 expression in muscle. We have confirmed that a 10-fold increase in UCP3 mRNA levels occurs in rat quadriceps muscle between 12 and 24 h of food removal. A less consistent twofold increase in muscle UCP2 mRNA levels was observed in animals fasted for up to 72 h. Administration of recombinant leptin to prevent a fall in circulating leptin levels did not eliminate the fasting-induced increase in quadriceps UCP3 expression. Administration of a high dose of glucocorticoid to fed animals to mimic the increase in corticosterone induced by fasting did not reproduce the increase in UCP3 expression observed in fasted animals. In contrast, elevation of circulating free fatty acid levels in fed animals by Intralipid plus heparin infusion caused significant increases in the UCP3/actin mRNA ratio compared with saline-infused fed controls in both extensor digitorum longus (2.01 ± 0.34 vs. 0.68 ± 0.11, P = 0.002) and soleus muscles (0.31 ± 0.07 vs. 0.09 ± 0.02, P = 0.014). We conclude that free fatty acids are a potential mediator of the increase in muscle UCP3 expression that occurs during fasting. This seemingly paradoxical induction of UCP3 may be linked to the use of free fatty acid as a fuel rather than an increased need of the organism to dissipate energy.

  • Received October 28, 1997.
  • Revision received November 19, 1997.
  • Accepted November 19, 1997.
  • Copyright © 1998 by the American Diabetes Association
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February 1998, 47(2)
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Elevated Free Fatty Acids Induce Uncoupling Protein 3 Expression in Muscle: A Potential Explanation for the Effect of Fasting
David S Weigle, Leah E Selfridge, Michael W Schwartz, Randy J Seeley, David E Cummings, Peter J Havel, Joseph L Kuijper, Hector BeltrandelRio
Diabetes Feb 1998, 47 (2) 298-302; DOI: 10.2337/diab.47.2.298

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Elevated Free Fatty Acids Induce Uncoupling Protein 3 Expression in Muscle: A Potential Explanation for the Effect of Fasting
David S Weigle, Leah E Selfridge, Michael W Schwartz, Randy J Seeley, David E Cummings, Peter J Havel, Joseph L Kuijper, Hector BeltrandelRio
Diabetes Feb 1998, 47 (2) 298-302; DOI: 10.2337/diab.47.2.298
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