Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors.
The adiponectin receptors AdipoR1 and AdipoR2 have been identified to mediate the insulin-sensitizing effects of adiponectin. Although AdipoR2 was suggested to be the main receptor for this adipokine in hepatocytes, AdipoR1 protein is highly abundant in primary human hepatocytes and hepatocytic cell lines. Nuclear receptors are main regulators of lipid metabolism and activation of peroxisome proliferator-activated receptor alpha and gamma, retinoid X receptor (RXR), and liver X receptor (LXR) by specific ligands may influence AdipoR1 abundance. AdipoR1 protein is neither altered by RXR or LXR agonists nor by pioglitazone. In contrast, fenofibric acid reduces AdipoR1 whereas hepatotoxic troglitazone upregulates AdipoR1 protein in HepG2 cells. Taken together this work shows for the first time that AdipoR1 protein is expressed in human hepatocytes but that it is not a direct target gene of nuclear receptors. Elevated AdipoR1 induced by hepatotoxic troglitazone may indicate a role of this receptor in adiponectin-mediated beneficial effects in liver damage.
Neumeier
Markus
M
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
Weigert
Johanna
J
Schäffler
Andreas
A
Weiss
Thomas
T
Kirchner
Stefan
S
Laberer
Sabine
S
Schölmerich
Jürgen
J
Buechler
Christa
C
D052242:Adiponectin / Q000494:pharmacology; D000077556:Alitretinoin; D000818:Animals; D016466:CHO Cells; D018938:Caco-2 Cells; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000819:agonists; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000494:pharmacology; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha / Q000819:agonists; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D000077205:Pioglitazone; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D047488:Retinoid X Receptors / Q000819:agonists; D045162:Thiazolidinediones / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D000077288:Troglitazone; D015854:Up-Regulation
C475418:ADIPOR1 protein, human; D052242:Adiponectin; D002839:Chromans; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D047492:Peroxisome Proliferator-Activated Receptors; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D000077556:Alitretinoin; D014212:Tretinoin; C007997:25-hydroxycholesterol; C006012:fenofibric acid; D000077288:Troglitazone; D011345:Fenofibrate; D000077205:Pioglitazone