Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hanhoff, T; Benjamin, S; Borchers, T; Spener, F.
Branched-chain fatty acids as activators of peroxisome proliferator-activated receptors
EUR J LIPID SCI TECHNOL. 2005; 107(10): 716-729.
Doi: 10.1002/ejit.200401076
Web of Science
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- Führende Autor*innen der Med Uni Graz
- Spener Friedrich
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- Abstract:
- We observed earlier that phytanic acid activated subtype alpha of the peroxisome proliferator-activated receptor (PPAR) via the cytosolic liver-type fatty acid-binding protein (L-FABP). In a further search for minor lipid nutrients that interact with genes, we explored here the potential of branched-chain fatty acids to serve as agonists for the PPAR subtypes alpha, beta and gamma in rodent and human molecular test systems. Beyond chlorophyll-derived pristanic and phytanic acids, bacteria-derived iso- and anteiso-fatty acids and avian-derived 'uropygial' fatty acids were tested by transactivation assay. In addition, we studied binding of these fatty acids to recombinantly expressed PPAR ligand binding domains (LBDs) and to L-FABP by competition with fluorescent parinaric acid. In contrast to single methyl-branched agonists, multi methyl-branched fatty acids had high transactivation potentials in either test system; in addition, some agonists of the latter were highly subtype selective. Multi methyl-branched chain fatty acids were superior activators of human PPAR alpha, a preference not seen in the murine test system. High-affinity binding of isoprenoid-derived pristanic and phytanic acids to PPAR gamma-LBD and to L-FABP was observed, and also of pristanic acid to PPAR alpha-LBD. Polyketidic uropygial fatty acids bound to PPAR gamma-LBD only, though weakly. As both isoprenoid and polyketidic fatty acids showed high activation potentials, it became clear that binding data determined in vitro cannot predict biological activity as determined by transactivation assay. For pristanic acid, however, a signalling path similar to that found for phytanic acid can be concluded. Taken together, multi methyl-branched fatty acids of the human food chain can affect cellular metabolism through regulating gene expression.
- Find related publications in this database (Keywords)
- uropygial gland
- chlorophyll
- binding
- transactivation
- PPAR