Ampk activation by a-769662 and 991 does not affect catecholamine-induced lipolysis in human adipocytes

Research output: Contribution to journalJournal articlepeer-review

  • Franziska Kopietz
  • Christine Berggreen
  • Sara Larsson
  • Johanna Säll
  • Mikael Ekelund
  • Sakamoto, Kei
  • Eva Degerman
  • Cecilia Holm
  • Olga Göransson

Activation of AMP-activated protein kinase (AMPK) is considered an attractive strategy for the treatment of type 2 diabetes. Favorable metabolic effects of AMPK activation are mainly observed in skeletal muscle and liver tissue, whereas the effects in human adipose tissue are only poorly understood. Previous studies, which largely employed the AMPK activator 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), suggest an antilipolytic role of AMPK in adipocytes. The aim of this work was to reinvestigate the role of AMPK in the regulation of lipolysis, using the novel allosteric small-molecule AMPK activators A-769662 and 991, with a focus on human adipocytes. For this purpose, human primary subcutaneous adipocytes were treated with A-769662, 991, or AICAR, as a control, before being stimulated with isoproterenol. AMPK activity status, glycerol release, and the phosphorylation of hormone-sensitive lipase (HSL), a key regulator of lipolysis, were then monitored. Our results show that both A-769662 and 991 activated AMPK to a level that was similar to, or greater than, that induced by AICAR. In contrast to AICAR, which as expected was antilipolytic, neither A-769662 nor 991 affected lipolysis in human adipocytes, although 991 treatment led to altered HSL phosphorylation. Furthermore, we suggest that HSL Ser660 is an important regulator of lipolytic activity in human adipocytes. These data suggest that the antilipolytic effect observed with AICAR in previous studies is, at least to some extent, AMPK independent.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume315
Issue number5
Pages (from-to)E1075-E1085
ISSN0193-1849
DOIs
Publication statusPublished - Nov 2018
Externally publishedYes

    Research areas

  • Allosteric small-molecule AMPK activators, AMP-activated protein kinase, Hormone-sensitive lipase, Human adipocytes, Lipolysis

ID: 238432653