title: Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1α and AMPKα.
abstract: BACKGROUND
  Brown adipose tissue thermogenic program includes complex molecular and structural changes. However, energetic aspects of this process are poorly depicted.
  
  
  METHODS
  We investigated time-dependent reprogramming of interscapular brown adipose tissue (IBAT) energy metabolism during cold-acclimation, as well as the effects of nitric oxide (()NO) on those changes. Rats were exposed to cold (4±1°C) for periods of 1, 3, 7, 12, 21, and 45days, and divided into three groups: control, treated with L-arginine, and treated with N(ω)-nitro-L-arginine methyl ester (L-NAME).
  
  
  RESULTS
  In the early phase of cold-acclimation (up to 7days), the protein levels of all metabolic parameters and oxidative phosphorylation components were below the control. However, metabolic parameters and respiratory chain components entered a new homeostatic level in the late phase of cold-acclimation. These changes were accompanied with increased protein levels of phospho-AMP-dependent protein kinase-α (phospho-AMPKα) on the first day of cold-acclimation, and hypoxia-inducible factor-1α (HIF-1α) throughout early cold-acclimation. L-arginine positively affected protein expression of enzymes involved in glucose metabolism and β-oxidation of fatty acids in the early phase of cold-acclimation, and oxidative phosphorylation components throughout cold-acclimation. In contrast, L-NAME had the opposite effects.
  
  
  CONCLUSIONS
  Results suggest that IBAT structural remodeling is followed by energy metabolism reprogramming, which control might be orchestrated by the action of AMPKα and HIF-1α. Data also indicated the involvement of L-arginine-()NO in the regulation of IBAT metabolism.
  
  
  CONCLUSIONS
  Results obtained in this study might be of great importance for elucidating regulatory pathways governing energy metabolism in both physiological and pathophysiological states.
authors.affiliation: University of Belgrade, Department of Physiology, Institute for Biological Research "Sinisa Stankovic", Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Vucetic
authors.forename: Vesna
authors.initials: V
authors.lastname: Otasevic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korac
authors.forename: Ana
authors.initials: A
authors.lastname: Stancic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jankovic
authors.forename: Milica
authors.initials: M
authors.lastname: Markelic
authors.forename: Igor
authors.initials: I
authors.lastname: Golic
authors.forename: Ksenija
authors.initials: K
authors.lastname: Velickovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Buzadzic
authors.forename: Bato
authors.initials: B
authors.lastname: Korac
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000222:Adaptation, Physiological; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002952:Citric Acid Cycle; D003080:Cold Temperature; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D005947:Glucose / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D010085:Oxidative Phosphorylation; D051381:Rats
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D005947:Glucose