title: Tissue-specific differences in inflammatory infiltrate and matrix metalloproteinase expression in adipose tissue and liver of mice with diet-induced obesity.
abstract: OBJECTIVE
  While low grade inflammation persists in both visceral fat and hepatic tissue in obesity, these changes often result in progressive disease and fibrosis only in the liver and not in adipose tissue. We hypothesized that a tissue-specific difference in obesity-induced inflammatory cell infiltrate may be responsible for such organ difference in susceptibility to fibrosis.
  
  
  METHODS
  Mice were fed either standard chow or a high fat diet over 19 weeks. Hepatic steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. Immunohistochemistry staining for macrophage subsets and quantitative reverse transcription-polymerase chain reaction for matrix metalloproteinase (MMP)- and fibrosis-related gene expression was performed in paired livers and visceral (epididymal) fat pads at early (9 weeks) and advanced (19 weeks) stages of progressive diet-induced obesity.
  
  
  RESULTS
  Up to 19 weeks of high fat feeding led to the development of obesity and hepatic steatosis, as well as increased gene expression of Mmp12, Mmp13 and Timp1 in predominantly adipose tissue, and to a lesser extent of liver tissue. In contrast to visceral fat, cell counts for macrophages as well as profibrogenic gene signaling in liver tissue during development of diet-induced obesity remained largely unchanged.
  
  
  CONCLUSIONS
  Development of diet-induced obesity in the mouse increased inflammatory macrophages counts in adipose tissue rather than the liver. This was associated with greater increases in MMP expression in adipose tissue compared with liver. We propose that attenuated hepatic MMP expression in livers and adipose tissue of obese mice shifts the balance of fibrogenesis/fibrolysis and predispose the liver to development of fibrosis.
authors.affiliation: Department of Surgery and Vascular Biology Program, Children's Hospital Boston, Harvard Medical School             Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA             Department of Surgery, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Vincent E
authors.initials: VE
authors.lastname: de Meijer
authors.forename: Deanna Y
authors.initials: DY
authors.lastname: Sverdlov
authors.forename: Hau D
authors.initials: HD
authors.lastname: Le
authors.forename: Yury
authors.initials: Y
authors.lastname: Popov
authors.forename: Mark
authors.initials: M
authors.lastname: Puder