AMP-activated protein kinase activation suppresses leptin expression independently of adipogenesis in primary murine adipocytes
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Adipogenesis, defined as the development of mature adipocytes from stem cell precursors, is vital for the expansion, turnover and health of adipose tissue. Loss of adipogenic potential in adipose stem cells, or impairment of adipogenesis is now recognised as an underlying cause of adipose tissue dysfunction and is associated with metabolic disease. In this study, we sought to determine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved master regulator of energy homeostasis, in adipogenesis. Primary murine adipose-derived stem cells were treated with a small molecule AMPK activator (BI-9774) during key phases of adipogenesis, to determine the effect of AMPK activation on adipocyte commitment, maturation and function. To determine the contribution of the repression of lipogenesis by AMPK in these processes, we compared the effect of pharmacological inhibition of acetyl-CoA carboxylase (ACC). We show that AMPK activation inhibits adipogenesis in a time- and concentration-dependent manner. Transient AMPK activation during adipogenic commitment leads to a significant, ACC-independent, repression of adipogenic transcription factor expression. Furthermore, we identify a striking, previously unexplored inhibition of leptin gene expression in response to both short-term and chronic AMPK activation irrespective of adipogenesis. These findings reveal that in addition to its effect on adipogenesis, AMPK activation switches off leptin gene expression in primary mouse adipocytes independently of adipogenesis. Our results identify leptin expression as a novel target of AMPK through mechanisms yet to be identified.
Date Issued
2024-03
Date Acceptance
2024-02-04
Citation
Biochemical Journal, 2024, 481 (5), pp.345-362
ISSN
0264-6021
Publisher
Portland Press
Start Page
345
End Page
362
Journal / Book Title
Biochemical Journal
Volume
481
Issue
5
Copyright Statement
© 2024 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
License URL
Identifier
https://portlandpress.com/biochemj/article/481/5/345/234020/AMP-activated-protein-kinase-activation-suppresses
Subjects
AICAR
BEIGE ADIPOSE-TISSUE
Biochemistry & Molecular Biology
C/EBP
CELLS
HEPATIC STEATOSIS
INSULIN-RESISTANCE
Life Sciences & Biomedicine
OBESITY
PATHWAY
Science & Technology
TRANSCRIPTION
UPSTREAM
Publication Status
Published
Date Publish Online
2024-02-23