title: Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.
abstract: Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis.
  
  
  
  Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo2H incorporation from2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver.
  
  
  
  The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains.
  
  
  
  Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Flachs
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Adamcova
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Zouhar
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Marques
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Janovska
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Viegas
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal.
authors.forename: J G
authors.initials: JG
authors.lastname: Jones
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Bardova
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Svobodova
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Hansikova
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Kuda
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Rossmeisl
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: U
authors.initials: U
authors.lastname: Liisberg
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A G
authors.initials: AG
authors.lastname: Borkowska
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|BGI-Shenzhen, Shenzhen, China.
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|National Institute of Nutrition and Seafood Research, Bergen, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kopecky
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology*; D013851:Thinness / Q000235:genetics / Q000378:metabolism*
chemical_list: D008079:Lipoproteins, VLDL