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Papers In Press, published online ahead of print May 1, 2006
J. Lipid Res., doi:10.1194/jlr.M500459-JLR200

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Journal of Lipid Research, Vol. 47, 931-943, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

PPAR activators and fasting induce the expression of adipose differentiation-related protein in liver

Knut Tomas Dalen, Stine M. Ulven¹, Borghild M. Arntsen¹, Karianne Solaas and Hilde I. Nebb²

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, N-0316 Oslo, Norway

The online version of this article (available at http://www.jlr.org) contains additional figures.

Published, JLR Papers in Press, February 17, 2006.

¹ S. M. Ulven and B. M. Arntsen contributed equally to this work.

² To whom correspondence should be addressed. e-mail: h.i.nebb{at}medisin.uio.no

The adipose differentiation-related protein (ADFP)/adipophilin belongs to a family of PAT (for perilipin, ADFP, and TIP47) proteins that associate on the surface of lipid droplets (LDs). Except for LD association, a clear role for ADFP has not been found. We demonstrate that ADFP is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR) in mouse liver and rat and human hepatoma cells through a highly conserved direct repeat-1(DR-1) element. Although the ADFP mRNA is highly increased by a synthetic PPAR agonist, the ADFP protein is only substantially increased in cells containing LDs, such as hepatocytes incubated with fatty acids, and in livers of fasted mice. ADFP is induced by fasting even in the absence of a functional PPAR, in marked contrast to the PPAR target gene acyl-coenzyme A oxidase-1. Activation of LXRs, which stimulates LD formation through the activation of lipogenesis, does not affect ADFP mRNA levels. TIP47, another PAT member known to be expressed in liver, was unaffected by all treatments. This constitutively expressed PAT member seems to be less transcriptionally regulated than ADFP. These observations suggest that ADFP is primarily a fasting-induced protein in liver that coats the newly synthesized triacylglycerol-containing LDs formed during fasting.

Supplementary key words adipose differentiation-related protein • adipophilin • tail-interacting protein of 47 kDa • fatty liver • direct repeat-1 • peroxisome proliferator-activated receptor • peroxisome proliferator-activated receptor response element • promoter • triacylglycerol • lipid droplet

Abbreviations: ACO-1, acyl-coenzyme A oxidase-1; ADFP, adipose differentiation-related protein; CE, cholesterol ester; CMC, carboxymethyl cellulose; DR-1, direct repeat-1; LD, lipid droplet; ME-1, cytosolic malic enzyme-1; OA, oleic acid; PPAR, peroxisome proliferator-activated receptor; PPRE, peroxisome proliferator-activated receptor response element; RXR, retinoid X receptor; SREBP-1, sterol-regulatory element binding protein-1; TAG, triacylglycerol; TIP47, tail-interacting protein of 47 kDa; TTA, tetradecylthioacetic acid

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