title: Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice.
abstract: OBJECTIVE
  Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice.
  
  
  METHODS
  To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion).
  
  
  RESULTS
  In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation.
  
  
  CONCLUSIONS
  CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors: J S
authors: JS
authors: Teodoro
authors: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
authors: P
authors: P
authors: Zouhar
authors: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
authors: P
authors: P
authors: Flachs
authors: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
authors: K
authors: K
authors: Bardova
authors: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
authors: P
authors: P
authors: Janovska
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors: A P
authors: AP
authors: Gomes
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors: F V
authors: FV
authors: Duarte
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors: A T
authors: AT
authors: Varela
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Biology, University of Aveiro, Aveiro, Portugal.
authors: A P
authors: AP
authors: Rolo
authors: 1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors: C M
authors: CM
authors: Palmeira
authors: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
authors: J
authors: J
authors: Kopecký
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D059305:Diet, High-Fat; D004734:Energy Metabolism; D018149:Glucose Intolerance / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D002635:Chenodeoxycholic Acid