title: Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse.
abstract: AMPK (adenosine monophosphate-activated protein kinase), a key regulator of cellular energy metabolism and whole-body energy balance, is present in brown adipose tissue but its role in regulating the acute metabolic state and chronic thermogenic potential of this metabolically unique tissue is unknown. To address this, the AMPK signalling system in brown and white adipose tissue was studied in C57Bl/6 mice under control conditions, during acute and chronic cold exposure, and during chronic adrenergic stimulation. In control mice AMPK activity in brown adipose tissue was higher than in any tissue yet reported (3-fold the level in liver) secondary to a high level of expression of the alpha1 isoform. During the first day of cold, a time of intense non-shivering thermogenesis, AMPK activity remained at basal levels. However, chronic (>7 days) cold caused a progressive increase in brown adipose tissue AMPK activity secondary to increased expression of the alpha1 isoform. To investigate the signalling pathway involved, noradrenaline (norepinephrine) and the beta(3)-adrenergic-specific agonist CL 316, 243 were given for 14 days. This increased uncoupling protein-1 content in brown adipose tissue, but not AMPK activity. In white adipose tissue 15 days of cold increased alpha1 AMPK activity 98 +/- 20%, an effect reproduced by chronic noradrenaline or CL 316 243. We conclude that chronic cold not only increases AMPK activity in brown and white adipose tissue, but that it does so via distinct signalling pathways. Our data are consistent with AMPK acting primarily as a regulator of chronic thermogenic potential in brown adipose tissue, and not in the acute activation of non-shivering thermogenesis.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI 53706, USA. kws@medicine.wisc.edu.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Mulligan
authors.forename: Asensio A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Annette M
authors.initials: AM
authors.lastname: Stewart
authors.forename: Hannah V
authors.initials: HV
authors.lastname: Carey
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Saupe
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000064:Acclimatization / Q000502:physiology*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018663:Adrenergic Agents; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D000103:Acetyl-CoA Carboxylase