AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue.

Autor:	Chuang SJ; Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium., Johanns M; Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium., Pyr Dit Ruys S; Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium., Steinberg GR; Centre for Metabolism, Obesity and Diabetes Research, Department of Medicine and Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada., Kemp BE; St. Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.; Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, VIC, Australia., Viollet B; Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France., Rider MH; Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2021 Nov 12; Vol. 478 (21), pp. 3869-3889.
DOI:	10.1042/BCJ20210411
Abstrakt:	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. (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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