Increased expression of PPARγ in high fat diet-induced liver steatosis in mice

• DOI: 10.1016/j.bbrc.2005.08.070
• Publication Date: 2005-08-20T11:18:35Z
• Authors: Mitsutaka Inoue; Takaaki Ohtake; Wataru Motomura; Nobuhiko Takahashi; Yayoi Hosoki; Shigeki Miyoshi; Yasuaki Suzuki; Hiroyuki Saito; Yutaka Kohgo; Toshikatsu Okumura
• Keywords: Male; 0301 basic medicine; Base Sequence; Gene Expression Profiling; Body Weight; Dietary Fats; Fatty Liver; Mice, Inbred C57BL; PPAR gamma; Mice; 03 medical and health sciences; Liver; Animals; RNA, Messenger; Cyclic AMP Response Element-Binding Protein; DNA Primers

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.