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AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue
Chuang, Sheng-Ju Johanns, Manuel dit Ruys, Sébastien Steinberg, Gregory R. Kemp, Bruce Ernest E. Viollet, Benoit Rider, Mark
Chuang, Sheng-Ju
Johanns, Manuel
dit Ruys, Sébastien
Steinberg, Gregory R.
Kemp, Bruce Ernest E.
Viollet, Benoit
Rider, Mark
Citations
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Author
Chuang, Sheng-Ju
Johanns, Manuel
dit Ruys, Sébastien
Steinberg, Gregory R.
Kemp, Bruce Ernest E.
Viollet, Benoit
Rider, Mark
Johanns, Manuel
dit Ruys, Sébastien
Steinberg, Gregory R.
Kemp, Bruce Ernest E.
Viollet, Benoit
Rider, Mark
Abstract
The effects of small-molecule AMP-activated protein kinase (AMPK) activators in rat epididymal adipocytes were compared. SC4 was the most effective and submaximal doses of SC4 and 5-amino-4-imidazolecarboxamide (AICA) riboside were combined to study the effects of AMPK activation in white adipose tissue (WAT). Incubation of rat adipocytes with SC4 + AICA riboside inhibited noradrenaline-induced lipolysis and decreased hormone-sensitive lipase (HSL) Ser563 phosphorylation, without affecting HSL Ser565 phosphorylation. Preincubation of fat pads from wild-type (WT) mice with SC4 + AICA riboside inhibited insulin-stimulated lipogenesis from glucose or acetate and these effects were lost in AMPKα1 knockout (KO) mice, indicating AMPKα1 dependency. Moreover, in fat pads from acetyl-CoA carboxylase (ACC)1/2 S79A/S212A double knockin versus WT mice, the effect of SC4 + AICA riboside to inhibit insulin-stimulated lipogenesis from acetate was lost, pinpointing ACC as the main AMPK target. Treatment with SC4 + AICA riboside decreased insulin-stimulated glucose uptake, an effect that was still observed in fat pads from AMPKα1 KO versus WT mice, suggesting the effect was partly AMPKα1-independent. SC4 + AICA riboside treatment had no effect on the insulin-induced increase in palmitate esterification nor on sn-glycerol-3-phosphate-O-acyltransferase activity. Therefore in WAT, AMPK activation inhibits noradrenaline-induced lipolysis and suppresses insulin-stimulated lipogenesis primarily by inactivating ACC and by inhibiting glucose uptake.
Keywords
ACC, AMPK, de novo lipogenesis, glucose transport, GPAT, TBC1D4
Date
2022
Type
Journal article
Journal
Biochemical Journal
Book
Volume
478
Issue
21
Page Range
3869-3889
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as green open access
License
File Access
Controlled
Open
Open
Notes
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