Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Differential regulation of fatty acid elongation enzymes in brown adipocytes imply an unique role for Elovl3 during increased fatty acid oxidation
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
2005 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 289, 517-526 p.Article in journal (Refereed) Published
Abstract [en]

The expression of the Elovl3 gene, which belongs to the Elovl gene family coding for microsomal enzymes involved in very long-chain fatty acid (VLCFA) elongation, is dramatically increased in mouse brown adipose tissue upon cold stimulation. In the present study, we show that the cold-induced Elovl3 expression is under the control of peroxisome proliferator-activated receptor- (PPAR) and that this regulation is part of a fundamental divergence in the regulation of expression for the different members of the Elovl gene family. In cultured brown adipocytes, a mixture of norepinephrine, dexamethasone, and the PPAR ligand Wy-14643, which rendered the adipocytes a high oxidative state, was required for substantial induction of Elovl3 expression, whereas the same treatment suppressed Elovl1 mRNA levels. The nuclear liver X receptor (LXR) has been implicated in the control of fatty acid synthesis and subsequent lipogenic processes in several tissues. This regulation is also exerted in part by sterol regulatory element-binding protein (SREBP-1), which is a target gene of LXR. We found that stimulation of Elovl3 expression was independent of LXR and SREBP-1 activation. In addition, exposure to the LXR agonist TO-901317 increased nuclear abundance of LXR and mature SREBP-1 as well as expression of the elongases Lce and Elovl1 in a lipogenic fashion but repressed Elovl3 expression. A functional consequence of this was seen on the level of esterified saturated fatty acids, such as C22:0, which was coupled to Elovl3 expression. These data demonstrate differential transcriptional regulation and concomitantly different functional roles for fatty acid elongases in lipid metabolism of brown adipocytes, which reflects the metabolic status of the cells.

Place, publisher, year, edition, pages
2005. Vol. 289, 517-526 p.
Keyword [en]
elongase; brown adipose tissue; gene expression; very long-chain fatty acid
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-23614DOI: 10.1152/ajpendo.00045.2005 0193-1849/05OAI: oai:DiVA.org:su-23614DiVA: diva2:193388
Note
Part of urn:nbn:se:su:diva-398Available from: 2005-03-01 Created: 2005-03-01 Last updated: 2010-09-21Bibliographically approved
In thesis
1. Elovl3 and very long chain fatty acids; role in metabolism
Open this publication in new window or tab >>Elovl3 and very long chain fatty acids; role in metabolism
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fatty acids (FA) are important in several aspects of cellular function, for example as structural molecules and metabolic substrates. The bulk of FA up to 16 carbons (palmitic acid) in length are synthesised by a cytosolic enzyme complex called fatty acid synthase (FAS), while FA can be further elongated into very long-chain fatty acids (VLCFA) by membrane-bound enzymes in the endoplasmatic reticulum (ER). Individual enzymes perform the four different steps of the elongation cycle to extend VLCFA, where condensation enzymes (first step) are suggested to be rate-limiting as well as in control of substrate specificity. Six mammalian condensation enzymes, encoded by Elovl (Elogation of very long chain fatty acids) genes in mouse, have presently been identified which suggests multiple elongation pathways.

In this report, I present data from studies performed mainly in brown adipose tissue and skin on the role of ELOVL3 in metabolic and structure-related processes. This enzyme is suggested to be involved in the synthesis of saturated and monounsaturated VLCFA, which are incorporated into different classes of lipids. Acyl-specific structural functions of sphingolipids, essential for proper membrane integrity, constitute a requirement for endogenous synthesis of VLCFA. We have demonstrated complementary functions between yeast and murine elongation enzymes in the synthesis of sphingolipids with corresponding alterations in cell viability. This indicates a conserved function for elongation enzymes in eukaryotic cells, which implicates cellular growth and maintenance of membrane structures.

Investigations of the lipid composition in Elovl3-ablated mice, generated by homologous recombination, support a role for ELOVL3 in the synthesis of neutral lipids, such as triglycerides and sterol-esters. The phenotype of these mice includes impaired skin barrier function and altered VLCFA elongation activity in liver and brown adipose tissue, which is consistent with the tissue-specific expression pattern of this gene.

Regulation of Elovl3 mRNA expression in brown adipocytes was found to differ from what was seen for other Elovl gene family members, which suggests divergent functional roles within the family of elongases. Elovl3 expression correlated with a high oxidative state, therefore, the function of this enzyme may be to replenish specific lipids under conditions of intense FA turnover. In addition, channeling of metabolic substrates is altered in brown adipocytes lacking ELOVL3, indicating important functions of specific VLCFA in nutritional homeostasis and substrate utilization.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2005. 150 p.
Keyword
Fatty acids metabolism elongation
National Category
Physiology
Identifiers
urn:nbn:se:su:diva-398 (URN)91-7155-012-7 (ISBN)
Public defence
2005-03-22, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2005-03-01 Created: 2005-03-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
The Wenner-Gren Institute
In the same journal
American Journal of Physiology. Endocrinology and Metabolism
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 119 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf