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Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes.

Publication ,  Journal Article
Cortez-Pinto, H; Zhi Lin, H; Qi Yang, S; Odwin Da Costa, S; Diehl, AM
Published in: Gastroenterology
May 1999

BACKGROUND & AIMS: Hepatic steatosis reflects the accumulation of triglycerides and free fatty acids in hepatocytes. Although lipids and their metabolites are potentially hepatotoxic, the absence of overt injury in fatty livers suggests that adaptive responses to lipid accumulation occur. Fatty acids induce mitochondrial uncoupling proteins (UCP) 2 and 3 in muscle and fat, providing a mechanism to dispose of excessive fatty acids. Although hepatocytes do not normally express uncoupling proteins, UCP-2 is expressed in hepatocytes of genetically obese mice with fatty livers, suggesting that lipids also induce UCP-2 in hepatocytes. METHODS: To test whether lipids up-regulate hepatocyte UCP-2, cultures of rat hepatocytes were treated with lipid emulsions, linoleic or oleic acid, and UCP-2 expression was evaluated by Northern blotting and immunocytochemistry. Because increased reactive oxygen species (ROS) production may contribute to lipid-related UCP-2 induction, the DNA-binding activity of the ROS-activated transcription factor, NF-kappaB, was measured, and the effects of tert-butyl hydroperoxide (TBHP) and glutathione (GSH) on UCP-2 induction were also assessed. RESULTS: Lipid emulsions increased the DNA-binding activity of NF-kappaB and resulted in a dose- and time-dependent induction of UCP-2 transcripts in cultured hepatocytes; after 24 hours, UCP-2 messenger RNA levels were increased 4.5-fold, and increased UCP-2 protein was shown by immunocytochemistry. Consistent with the possibility that ROS generated intracellularly during lipid metabolism participates in UCP-2 induction, addition of the cell-impermeable antioxidant GSH did not alter lipid-related induction of UCP-2. Furthermore, TBHP, which is known to increase hepatocyte mitochondrial ROS production, also increased UCP-2 messenger RNA levels. CONCLUSIONS: Lipids increase ROS and induce UCP-2 in hepatocytes. Thus, the liver may adapt to an excessive supply of lipid substrates by inducing UCP-2 to facilitate substrate disposal while constraining ROS production.

Duke Scholars

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

May 1999

Volume

116

Issue

5

Start / End Page

1184 / 1193

Location

United States

Related Subject Headings

  • tert-Butylhydroperoxide
  • Uncoupling Protein 2
  • Uncoupling Agents
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Proteins
  • Protein Biosynthesis
  • Oleic Acid
 

Citation

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ICMJE
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Cortez-Pinto, H., Zhi Lin, H., Qi Yang, S., Odwin Da Costa, S., & Diehl, A. M. (1999). Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes. Gastroenterology, 116(5), 1184–1193. https://doi.org/10.1016/s0016-5085(99)70022-3
Cortez-Pinto, H., H. Zhi Lin, S. Qi Yang, S. Odwin Da Costa, and A. M. Diehl. “Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes.Gastroenterology 116, no. 5 (May 1999): 1184–93. https://doi.org/10.1016/s0016-5085(99)70022-3.
Cortez-Pinto H, Zhi Lin H, Qi Yang S, Odwin Da Costa S, Diehl AM. Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes. Gastroenterology. 1999 May;116(5):1184–93.
Cortez-Pinto, H., et al. “Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes.Gastroenterology, vol. 116, no. 5, May 1999, pp. 1184–93. Pubmed, doi:10.1016/s0016-5085(99)70022-3.
Cortez-Pinto H, Zhi Lin H, Qi Yang S, Odwin Da Costa S, Diehl AM. Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes. Gastroenterology. 1999 May;116(5):1184–1193.
Journal cover image

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

May 1999

Volume

116

Issue

5

Start / End Page

1184 / 1193

Location

United States

Related Subject Headings

  • tert-Butylhydroperoxide
  • Uncoupling Protein 2
  • Uncoupling Agents
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Proteins
  • Protein Biosynthesis
  • Oleic Acid