Advanced

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

Kopietz, Franziska LU ; Berggreen, Christine LU ; Larsson, Sara LU ; Säll, Johanna LU ; Ekelund, Mikael LU ; Sakamoto, Kei; Degerman, Eva LU ; Holm, Cecilia LU and Göransson, Olga LU (2018) In American Journal of Physiology - Endocrinology and Metabolism 315(5). p.1075-1085
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology - Endocrinology and Metabolism
volume
315
issue
5
pages
1075 - 1085
publisher
American Physiological Society
external identifiers
  • scopus:85056603779
ISSN
1522-1555
DOI
10.1152/ajpendo.00110.2018
language
English
LU publication?
yes
id
7fa160fb-6841-4dde-9f53-69cac790954b
date added to LUP
2018-10-31 19:11:32
date last changed
2019-09-17 04:42:27
@article{7fa160fb-6841-4dde-9f53-69cac790954b,
  abstract     = {<p>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.</p>},
  author       = {Kopietz, Franziska and Berggreen, Christine and Larsson, Sara and Säll, Johanna and Ekelund, Mikael and Sakamoto, Kei and Degerman, Eva and Holm, Cecilia and Göransson, Olga},
  issn         = {1522-1555},
  language     = {eng},
  month        = {09},
  number       = {5},
  pages        = {1075--1085},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Endocrinology and Metabolism},
  title        = {AMPK activation by A-769662 and 991 does not affect catecholamine-induced lipolysis in human adipocytes},
  url          = {http://dx.doi.org/10.1152/ajpendo.00110.2018},
  volume       = {315},
  year         = {2018},
}