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

Biochem Biophys Res Commun. 2005 Oct 14;336(1):215-22. doi: 10.1016/j.bbrc.2005.08.070.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Weight
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Primers
  • Dietary Fats / administration & dosage*
  • Fatty Liver / etiology
  • Fatty Liver / genetics
  • Fatty Liver / metabolism*
  • Gene Expression Profiling
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • RNA, Messenger / genetics


  • Cyclic AMP Response Element-Binding Protein
  • DNA Primers
  • Dietary Fats
  • PPAR gamma
  • RNA, Messenger