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ludc web

Sara Larsson

Research engineer

ludc web

AMPK activation by A-769662 and 991 does not affect catecholamine-induced lipolysis in human adipocytes

Author

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

Summary, in English

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-carboxamide-1-D-ribofuranoside (AICAR), suggest an anti-lipolytic role of AMPK in adipocytes. The aim of this work was to re-investigate 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, was then monitored. Our results show that both A-769662 and 991 activated AMPK to a level which was similar to, or greater than that induced by AICAR. In contrast to AICAR, which as expected was anti-lipolytic, neither A-769662 nor 991 affected lipolysis in human adipocytes, although 991 treatment lead 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 anti-lipolytic effect observed with AICAR in previous studies is, at least to some extent, AMPK-independent.

Department/s

  • Protein Phosphorylation
  • Department of Experimental Medical Science
  • Adaptive Immunity
  • Diabetes and Brain Function
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Surgery (Lund)
  • Surgery
  • Insulin Signal Transduction
  • Molecular Endocrinology

Publishing year

2018-09-25

Language

English

Pages

1075-1085

Publication/Series

American Journal of Physiology - Endocrinology and Metabolism

Volume

315

Issue

5

Document type

Journal article

Publisher

American Physiological Society

Topic

  • Cell and Molecular Biology
  • Physiology
  • Pharmacology and Toxicology

Status

Published

Research group

  • Protein Phosphorylation
  • Adaptive Immunity
  • Diabetes and Brain Function
  • Surgery
  • Insulin Signal Transduction
  • Molecular Endocrinology

ISBN/ISSN/Other

  • ISSN: 1522-1555