PPARalpha activators and fasting induce the expression of adipose differentiation-related protein in liver.
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 alpha (PPARalpha) 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 PPARalpha 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 PPARalpha, in marked contrast to the PPARalpha 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.
Dalen
Knut Tomas
KT
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
Ulven
Stine M
SM
Arntsen
Borghild M
BM
Solaas
Karianne
K
Nebb
Hilde I
HI
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000187:drug effects; D004435:Eating; D005215:Fasting / Q000502:physiology*; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D009539:Nicotinic Acids / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha / Q000502:physiology*; D000070780:Perilipin-2; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D047488:Retinoid X Receptors / Q000819:agonists; D013449:Sulfonamides / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D004268:DNA-Binding Proteins; D005227:Fatty Acids; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D008565:Membrane Proteins; D009539:Nicotinic Acids; D019301:Oleic Acid; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D000070780:Perilipin-2; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; C000602982:PLIN2 protein, human; C000602983:Plin2 protein, mouse; C000602984:Plin2 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C006253:pirinixic acid; C095104:LG 100268