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

• Main Authors: Knut Tomas Dalen, Stine M. Ulven, Borghild M. Arntsen, Karianne Solaas, Hilde I. Nebb
• Format: Article
• Language: English
• Published: Elsevier 2006-05-01
• Series: Journal of Lipid Research
• Subjects: adipose differentiation-related protein; adipophilin; tail-interacting protein of 47 kDa; fatty liver; direct repeat-1; peroxisome proliferator-activated receptor
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520332417

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 α (PPARα) 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 PPARα 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 PPARα, in marked contrast to the PPARα 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.