Katwan, O. J., Alghamdi, F., Almabrouk, T. A. , Mancini, S. J., Kennedy, S. , Oakhill, J. S., Scott, J. W. and Salt, I. P. (2019) AMP-activated protein kinase complexes containing the β2 regulatory subunit are upregulated during and contribute to adipogenesis. Biochemical Journal, 476(12), pp. 1725-1740. (doi: 10.1042/BCJ20180714) (PMID:31189568) (PMCID:PMC6595317)
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Abstract
AMP-activated protein kinase (AMPK) is a heterotrimer of α catalytic and β and γ regulatory subunits that acts to regulate cellular and whole-body nutrient metabolism. The key role of AMPK in sensing energy status has led to significant interest in AMPK as a therapeutic target for dysfunctional metabolism in type 2 diabetes, insulin resistance and obesity. Despite the actions of AMPK in liver and skeletal muscle being extensively studied, the role of AMPK in adipose tissue and adipocytes remains less well characterised. Small molecules that selectively influence AMPK heterotrimers containing specific AMPKβ subunit isoforms have been developed, including MT47-100, which selectively inhibits complexes containing AMPKβ2. AMPKβ1 and AMPKβ2 are the principal AMPKβ subunit isoforms in rodent liver and skeletal muscle respectively, yet the contribution of specific AMPKβ isoforms to adipose tissue function, however, remains largely unknown. This study therefore sought to determine the contribution of AMPKβ subunit isoforms to adipocyte biology, focussing on adipogenesis. AMPKβ2 was the principal AMPKβ isoform in 3T3-L1 adipocytes, isolated rodent adipocytes and human subcutaneous adipose tissue, as assessed by the contribution to total cellular AMPK activity. Downregulation of AMPKβ2 with siRNA inhibited lipid accumulation, cellular adiponectin levels and adiponectin secretion during 3T3-L1 adipogenesis, whereas downregulation of AMPKβ1 had no effect. Incubation of 3T3-L1 cells with MT47-100 selectively inhibited AMPK complexes containing AMPKβ2 whilst simultaneously inhibiting cellular lipid accumulation as well as cellular levels and secretion of adiponectin. Taken together, these data indicate that increased expression of AMPKβ2 is an important feature of efficient adipogenesis.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Alghamdi, Fatmah and Kennedy, Professor Simon and Mancini, Dr Sarah and ALMABROUK, Tarek Ali Mohamed and Salt, Dr Ian and Katwan, Omar Jassim |
Authors: | Katwan, O. J., Alghamdi, F., Almabrouk, T. A., Mancini, S. J., Kennedy, S., Oakhill, J. S., Scott, J. W., and Salt, I. P. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Life Sciences College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Biochemical Journal |
Publisher: | Portland Press |
ISSN: | 0264-6021 |
ISSN (Online): | 1470-8728 |
Published Online: | 26 June 2019 |
Copyright Holders: | Copyright © 2019 The Authors |
First Published: | First published in Biochemical Journal 476(12): 1725-1740 |
Publisher Policy: | Reproduced under a Creative Commons License |
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