AMP-activated protein kinase complexes containing the ?2 regulatory subunit are up-regulated during and contribute to adipogenesis.
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ABSTRACT: AMP-activated protein kinase (AMPK) is a heterotrimer of ?-catalytic and ?- and ?-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 the 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 AMPK? subunit isoforms have been developed, including MT47-100, which selectively inhibits complexes containing AMPK?2. AMPK?1 and AMPK?2 are the principal AMPK? subunit isoforms in rodent liver and skeletal muscle, respectively, yet the contribution of specific AMPK? isoforms to adipose tissue function, however, remains largely unknown. This study therefore sought to determine the contribution of AMPK? subunit isoforms to adipocyte biology, focussing on adipogenesis. AMPK?2 was the principal AMPK? isoform in 3T3-L1 adipocytes, isolated rodent adipocytes and human subcutaneous adipose tissue, as assessed by the contribution to total cellular AMPK activity. Down-regulation of AMPK?2 with siRNA inhibited lipid accumulation, cellular adiponectin levels and adiponectin secretion during 3T3-L1 adipogenesis, whereas down-regulation of AMPK?1 had no effect. Incubation of 3T3-L1 cells with MT47-100 selectively inhibited AMPK complexes containing AMPK?2 whilst simultaneously inhibiting cellular lipid accumulation as well as cellular levels and secretion of adiponectin. Taken together, these data indicate that increased expression of AMPK?2 is an important feature of efficient adipogenesis.
SUBMITTER: Katwan OJ
PROVIDER: S-EPMC6595317 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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