Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1 alpha and AMPK alpha

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 ((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.