title: Browning of white adipose tissue uncouples glucose uptake from insulin signaling.
abstract: Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite) adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1) expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Mössenböck
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany; Junior research group Metabolism and Stem Cell Plasticity, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Vegiopoulos
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rose
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: Sijmonsma
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance and Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schafmeier
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D007328:Insulin; D005947:Glucose