Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha
Korac, Aleksandra B
Markelić, Milica B
Velicković, Ksenija D
Buzadžić, Biljana J.
Korać, Bato M.
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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 ((center dot)NO) on those changes. Rats were exposed to cold (4 +/- 1 degrees C) for periods of 1, 3, 7, 12, 21. and 45 days, and divided into three groups: control, treated with L-arginine, and treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). Results: In the early phase of cold-acclimation (up to 7 days), 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-alpha (phospho-AMPK alpha) on the first day of cold-acclimation, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) throughout early cold-acclimation. L-arginine positively affected protein expression of enzymes involved in glucose metabolism and beta-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. Conclusion: Results suggest that IBAT structural remodeling is followed by energy metabolism reprogramming, which control might be orchestrated by the action of AMPK alpha and HIF-1 alpha. Data also indicated the involvement of L-arginine-(center dot)NO in the regulation of IBAT metabolism. General significance: Results obtained in this study might be of great importance for elucidating regulatory pathways governing energy metabolism in both physiological and pathophysiological states. (C) 2011 Elsevier B.V. All rights reserved.
Извор:Biochimica et Biophysica Acta-General Subjects, 2011, 1810, 12, -1261