Abstract
Despite its importance in terms of energy homeostasis, the role of AMP-activated protein kinase in adipose tissue remains controversial. Initial studies have described an anti-lipolytic role for AMP-activated protein kinase, whereas more recent studies have suggested the converse. Thus we have addressed the role of AMP-activated protein kinase in adipose tissue by modulating AMP-activated protein kinase activity in primary rodent adipocytes using pharmacological activators or by adenoviral expression of dominant negative or constitutively active forms of the kinase. We then studied the effects of AMP-activated protein kinase activity modulation on lipolytic mechanisms. Finally, we analyzed the consequences of a genetic deletion of AMP-activated protein kinase in mouse adipocytes. AMP-activated protein kinase activity in adipocytes is represented mainly by the alpha(1) isoform and is induced by all of the stimuli that increase cAMP in adipocytes, including fasting. When AMP-activated protein kinase activity is increased by 5-aminoimidazole-4-carboxamide-riboside, phenformin, or by the expression of a constitutively active form, isoproterenol-induced lipolysis is strongly reduced. Conversely, when AMP-activated protein kinase activity is decreased either by a dominant negative form or in AMP-activated protein kinase alpha(1) knock-out mice, lipolysis is increased. We present data suggesting that AMP-activated protein kinase acts on hormone-sensitive lipase by blocking its translocation to the lipid droplet. We conclude that, in mature adipocytes, AMP-activated protein kinase activation has a clear anti-lipolytic effect.
Highlights
AMP-activated protein kinase (AMPK)1 is a widely expressed serine/threonine kinase that is considered to act as an
Adipocytes Express AMPK Complexes Containing the ␣1 Catalytic Subunit—Because AMPK complexes contain one of the two catalytic subunits (␣1 or ␣2) that respond differently to various stimuli [6, 19], we first determined the nature of the catalytic subunit accounting for AMPK activity in adipose tissue
AMPK became a burning issue when it was discovered that its activation could have beneficial effects in the metabolic syndrome through an insulin-independent increase in muscle glucose utilization, decreased hepatic glucose production, and increased fatty acid oxidation in both muscle and liver
Summary
AMP-activated protein kinase (AMPK)1 is a widely expressed serine/threonine kinase that is considered to act as an. Short-term incubations of adipocytes with AICAR or phenformin, a closely related analog of metformin, activate AMPK as shown by the increase of the phosphorylation state of AMPK Thr-172 (Fig. 3B) and strongly inhibit the isoproterenol-induced lipolysis (Fig. 3A) in a parallel manner.
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