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

M. Vucetic, V. Otasevic, A. Korac, A. Stancic, A. Jankovic, M. Markelic, I. Golic, K. Velickovic, B. Buzadzic and B. Korac
Biochimica et Biophysica Acta (BBA) - General Subjects, 1810 (2011), 1252-1261.

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 45 days, and divided into three groups: control, treated with L-arginine, and treated with Nω-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-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. Conclusion. 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.

Keywords: brown adipose tissue, metabolism reprogramming, nitric oxide, phospho-AMPKα, HIF-1α

IF: 5.000
IF5: 3.883
MNTR classification: M21


  title = {Interscapular brown adipose tissue metabolic reprogramming during cold acclimation: Interplay of HIF-1$\alpha$ and AMPK$\alpha$},
  author = {Vucetic, Milica and Otasevic, Vesna and Korac, Aleksandra and Stancic, Ana and Jankovic, Aleksandra and Markelic, Milica and Golic, Igor and Velickovic, Ksenija and Buzadzic, Biljana and Korac, Bato},
  journal = {Biochimica et Biophysica Acta (BBA)-General Subjects},
  volume = {1810},
  number = {12},
  pages = {1252--1261},
  year = {2011}