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

Research output: Contribution to journalArticle

300 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)298-302
Number of pages5
JournalDiabetes
Volume47
Issue number2
StatePublished - 1998

Fingerprint

Nonesterified Fatty Acids
Fasting
Muscles
Leptin
Messenger RNA
Skeletal Muscle
Uncoupling Protein 3
Muscle Proteins
Thermogenesis
Quadriceps Muscle
Corticosterone
Energy Metabolism
Glucocorticoids
Heparin
Actins
Food

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Weigle, D. S., Selfridge, L. E., Schwartz, M. W., Seeley, R. J., Cummings, D. E., Havel, P. J., ... BeltrandelRio, H. (1998). Elevated free fatty acids induce uncoupling protein 3 expression in muscle: A potential explanation for the effect of fasting. Diabetes, 47(2), 298-302.

Elevated free fatty acids induce uncoupling protein 3 expression in muscle : A potential explanation for the effect of fasting. / Weigle, David S.; Selfridge, Leah E.; Schwartz, Michael W.; Seeley, Randy J.; Cummings, David E.; Havel, Peter J; Kuijper, Joseph L.; BeltrandelRio, Hector.

In: Diabetes, Vol. 47, No. 2, 1998, p. 298-302.

Research output: Contribution to journalArticle

Weigle, DS, Selfridge, LE, Schwartz, MW, Seeley, RJ, Cummings, DE, Havel, PJ, Kuijper, JL & BeltrandelRio, H 1998, 'Elevated free fatty acids induce uncoupling protein 3 expression in muscle: A potential explanation for the effect of fasting', Diabetes, vol. 47, no. 2, pp. 298-302.
Weigle, David S. ; Selfridge, Leah E. ; Schwartz, Michael W. ; Seeley, Randy J. ; Cummings, David E. ; Havel, Peter J ; Kuijper, Joseph L. ; BeltrandelRio, Hector. / Elevated free fatty acids induce uncoupling protein 3 expression in muscle : A potential explanation for the effect of fasting. In: Diabetes. 1998 ; Vol. 47, No. 2. pp. 298-302.
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