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

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Abstract

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Nestlé
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
  • Fysiologi
  • Farmakologi och toxikologi
Originalspråkengelska
Sidor (från-till)E1075-E1085
TidskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Volym315
Utgivningsnummer5
Tidigt onlinedatum2018 sep 25
StatusPublished - 2018
PublikationskategoriForskning
Peer review utfördJa