AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue
Journal article
Chuang, Sheng-Ju, Johanns, Manuel, dit Ruys, Sébastien, Steinberg, Gregory R., Kemp, Bruce Ernest E., Viollet, Benoit and Rider, Mark. (2022). AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue. Biochemical Journal. 478(21), pp. 3869-3889. https://doi.org/10.1042/BCJ20210411
Authors | Chuang, Sheng-Ju, Johanns, Manuel, dit Ruys, Sébastien, Steinberg, Gregory R., Kemp, Bruce Ernest E., Viollet, Benoit and Rider, Mark |
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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 |
Year | 2022 |
Journal | Biochemical Journal |
Journal citation | 478 (21), pp. 3869-3889 |
Publisher | Portland Press Ltd. |
ISSN | 0264-6021 |
Digital Object Identifier (DOI) | https://doi.org/10.1042/BCJ20210411 |
Scopus EID | 2-s2.0-85119977523 |
Open access | Published as green open access |
Research or scholarly | Research |
Page range | 3869-3889 |
Funder | National Health and Medical Research Council (NHMRC) |
Australian Research Council (ARC) | |
Author's accepted manuscript | License All rights reserved File Access Level Open |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 09 Nov 2021 |
Publication process dates | |
Accepted | 20 Oct 2021 |
Deposited | 20 Jan 2022 |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | NHMRC/1085460 |
ARC/DP170101196 |
https://acuresearchbank.acu.edu.au/item/8x491/ampk-activation-by-sc4-inhibits-noradrenaline-induced-lipolysis-and-insulin-stimulated-lipogenesis-in-white-adipose-tissue
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AM_Chuang_2021_AMPK_activation_by_SC4_inhibits_noradrenaline.pdf | |
License: All rights reserved | |
File access level: Open |
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