Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice.
The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor gamma (PPARgamma) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARgamma and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARgamma protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARgamma, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARgamma signaling pathway may be involved in the high fat diet-induced liver steatosis.
Inoue
Mitsutaka
M
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan.
Ohtake
Takaaki
T
Motomura
Wataru
W
Takahashi
Nobuhiko
N
Hosoki
Yayoi
Y
Miyoshi
Shigeki
S
Suzuki
Yasuaki
Y
Saito
Hiroyuki
H
Kohgo
Yutaka
Y
Okumura
Toshikatsu
T
D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004041:Dietary Fats; D047495:PPAR gamma; D012333:RNA, Messenger