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

• Published in: Journal of lipid research 2000-11, Vol.41 (11), p.1740-1751
• Main Authors: Helledie, T, Antonius, M, Sorensen, R V, Hertzel, A V, Bernlohr, D A, Kølvraa, S, Kristiansen, K, Mandrup, S
• Format: Article
• Language: English
• Subjects: 3T3 Cells; acyl-CoA-binding protein; adipocyte differentiation; adipocyte lipid-binding protein/a-FABP/aP2; Adipocytes - ultrastructure; Animals; Carrier Proteins - analysis; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell Differentiation; Cell Line; Cell Nucleus - chemistry; Cytoplasm - chemistry; Diazepam Binding Inhibitor; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Gene Expression; keratinocyte lipid-binding protein/e-FABP/MAL1; Ligands; Mice; Neoplasm Proteins; Nerve Tissue Proteins; Receptors, Cytoplasmic and Nuclear - physiology; tetradecylthioacetic acid; Transcription Factors - physiology; Transcriptional Activation; Transfection
• ISSN: 0022-2275
• DOI: 10.1016/s0022-2275(20)31967-2

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.