Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet.
The present study was performed to examine a role of adipose differentiation-related protein (ADRP) in the process of liver steatosis. Immunohistochemical findings indicated that ADRP expression is increased in the hepatocytes in patients with fatty liver when compared with normal liver. ADRP expression is localized in the surface of lipid droplets in the hepatocytes. Increased expression of ADRP mRNA and protein was similarly observed in fatty liver in ob/ob mice and the liver steatosis induced by high fat diet in mice. The up-regulation of ADRP mRNA and protein in the liver by high fat diet was identified in the surface of lipid droplets in a time-dependent manner. Recent studies demonstrated that up-regulation of PPARgamma in the hepatocytes is deeply involved in liver steatosis. To clarify whether ADRP expression is increased by PPARgamma activation in hepatocytes, we examined the effect of a PPARgamma ligand, troglitazone, on ADRP mRNA expression in HepG2 cells. ADRP mRNA expression was increased by troglitazone in dose- and time-dependent manners. All these results suggest that ADRP is up-regulated in liver steatosis in human and mice, and that high fat diet increases expression of ADRP through PPARgamma activation, followed by induction of liver steatosis.
Motomura
Wataru
W
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Inoue
Mitsutaka
M
Ohtake
Takaaki
T
Takahashi
Nubuhiko
N
Nagamine
Miho
M
Tanno
Satoshi
S
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
D000818:Animals; D002460:Cell Line; D004041:Dietary Fats / Q000378:metabolism*; D005234:Fatty Liver; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D047495:PPAR gamma / Q000378:metabolism*; D000070780:Perilipin-2; D013045:Species Specificity; D014018:Tissue Distribution; D015854:Up-Regulation
D004041:Dietary Fats; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D047495:PPAR gamma; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse