Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm

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Peroxisome proliferator-activated receptors (PPARs) are activated by a variety of fatty acids, eicosanoids, and hypolipidemic and insulin-sensitizing drugs. Many of these compounds bind avidly to members of a family of small lipid-binding proteins, the fatty acid-binding proteins (FABPs). Fatty acids are activated to CoA esters, which bind with high affinity to the acyl-CoA-binding protein (ACBP). Thus, the availability of known and potential PPAR ligands may be regulated by lipid-binding proteins. In this report we show by transient transfection of CV-1 cells that coexpression of ACBP and adipocyte lipid-binding protein (ALBP) exerts a ligand- and PPAR subtype-specific attenuation of PPAR-mediated trans-activation, suggesting that lipid-binding proteins, when expressed at high levels, may function as negative regulators of PPAR activation by certain ligands. Expression of ACBP, ALBP, and keratinocyte lipid-binding protein (KLBP) is induced during adipocyte differentiation, a process during which PPARgamma plays a prominent role. We present evidence that endogenous ACBP, ALBP, and KLBP not only localize to the cytoplasm but also exhibit a prominent nuclear localization in 3T3-L1 adipocytes. In addition, forced expression of ACBP, ALBP, and KLBP in CV-1 cells resulted in a substantial accumulation of all three proteins in the nucleus. These results suggest that lipid-binding proteins, contrary to the general assumption, may exert their action in the nucleus as well as in the cytoplasm.
Original languageEnglish
JournalJournal of Lipid Research
Issue number11
Pages (from-to)1740-51
Number of pages11
Publication statusPublished - 2000
Externally publishedYes

Bibliographical note

Keywords: 3T3 Cells; Adipocytes; Animals; Carrier Proteins; Cell Differentiation; Cell Line; Cell Nucleus; Cytoplasm; Diazepam Binding Inhibitor; Fatty Acid-Binding Proteins; Gene Expression; Ligands; Mice; Neoplasm Proteins; Nerve Tissue Proteins; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Transcriptional Activation; Transfection

ID: 11232127