title: Tissue Inhibitor Of Matrix Metalloproteinase-1 Is Required for High-Fat Diet-Induced Glucose Intolerance and Hepatic Steatosis in Mice.
abstract: BACKGROUND
  Plasma levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are elevated in obesity and obesity-related disorders, such as steatosis, but the metabolic role of TIMP-1 is unclear. Here we investigated how the presence or absence of TIMP-1 affected the development of diet-induced glucose intolerance and hepatic steatosis using the Timp1 null mice.
  
  
  METHODS
  Timp1 knockout (TKO) and wild type (TWT) mice were fed chow, high-fat diet (HFD) or intermediate fat and sucrose diet (IFSD). We determined body weight, body composition, lipid content of the liver, energy intake, energy expenditure, oral glucose tolerance, as well as insulin tolerance. In addition, the histology of liver and adipose tissues was examined and expression of selected genes involved in lipid metabolism and inflammation in liver and adipose tissues was determined by RT-qPCR.
  
  
  RESULTS
  TKO mice gained less weight and had lower energy efficiency than TWT mice when fed HFD, but not when fed chow or IFSD. Importantly, TKO mice were protected from development of HFD- as well as IFSD-induced glucose intolerance, hepatic steatosis, and altered expression of genes involved in hepatic lipid metabolism and inflammation.
  
  
  CONCLUSIONS
  Collectively, our results indicate that TIMP-1 contributes to the development of diet-induced hepatic steatosis and glucose intolerance and may be a potential therapeutic target.
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Even
authors.initials: E
authors.lastname: Fjære
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersen
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lene Secher
authors.initials: LS
authors.lastname: Myrmel
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus Koefoed
authors.initials: RK
authors.lastname: Petersen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Copenhagen, University of Copenhagen, Denmark.
authors.forename: Jakob Bondo
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hanne Sørup
authors.initials: HS
authors.lastname: Tastesen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Copenhagen, University of Copenhagen, Denmark; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria Unni
authors.initials: MU
authors.lastname: Rømer
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000209:etiology* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D005947:Glucose