AMP-activated protein kinase complexes containing the β2 regulatory subunit are up-regulated during and contribute to adipogenesis

AMP-activated protein kinase (AMPK) is a heterotrimer of alpha-catalytic and beta- and gamma-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 beta subunit isoforms have been developed, including MT47-100, which selectively inhibits complexes containing AMPK beta 2. AMPK beta 1 and AMPK beta 2 are the principal AMPK beta subunit isoforms in rodent liver and skeletal muscle, respectively, yet the contribution of specific AMPK beta isoforms to adipose tissue function, however, remains largely unknown. This study therefore sought to determine the contribution of AMPK beta subunit isoforms to adipocyte biology, focussing on adipogenesis. AMPK beta 2 was the principal AMPK beta 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 beta 2 with siRNA inhibited lipid accumulation, cellular adiponectin levels and adiponectin secretion during 3T3-L1 adipogenesis, whereas down-regulation of AMPK beta 1 had no effect. Incubation of 3T3-L1 cells with MT47-100 selectively inhibited AMPK complexes containing AMPK beta 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 beta 2 is an important feature of efficient adipogenesis.