Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat

Matejkova, Olga; Mustard, Kirsty J; Sponarova, Jana; Flachs, Pavel; Rossmeisl, Martin; Miksik, Ivan; Thomason-Hughes, Michaela; Grahame Hardie, D; Kopecky, Jan

doi:10.1016/j.febslet.2004.06.002

Cited by 66Adipose Tissue and MetabolismMetabolism, Diabetes, and CancerPeroxisome Proliferator-Activated Receptors

Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat

Matejkova, Olga, Mustard, Kirsty J, Sponarova, Jana, Flachs, Pavel, Rossmeisl, Martin, Miksik, Ivan, Thomason-Hughes, Michaela, Grahame Hardie, D +1 more·2004·FEBS Letters

DOI 10.1016/j.febslet.2004.06.002

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Abstract

The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that promotes catabolic and inhibits anabolic pathways. However, the role of AMPK in adipocytes is poorly understood. We show that transgenic expression of mitochondrial uncoupling protein 1 in white fat, which induces obesity resistance in mice, is associated with depression of cellular energy charge, activation of AMPK, downregulation of adipogenic genes, and increase in lipid oxidation. Activation of AMPK may explain the complex metabolic changes in adipose tissue of these animals and our results support a role for adipocyte AMPK in the regulation of storage of body fat.

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The best-known effect of mitochondrial uncouplers is a drop in ATP/AMP levels, which induces activation of the AMPK signaling pathway.
“In terms of cell signaling, the best-known effect of mitochondrial uncouplers is probably a drop in ATP/AMP levels, which induces the activation of the AMPK signaling pathway (Figure 1).”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [251]
Injection of DNP in C57BL/6 mice leads to suppression of the mTOR-PI3K-MAPK pathway.
“Injection of DNP in C57BL/6 mice leads to the suppression of this pathway [94,251] and to the upregulation of genes involved in autophagy, such as LC3B, p62, or Ulk1 [94].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [251]
The effect of mitochondrial uncouplers on ATP/AMP levels and AMPK activation has been found in multiple models and species, including white adipocytes, skeletal muscle cells, cancer cells, and neurons.
“This effect has been found in multiple models and species, including white adipocytes [91,251], skeletal muscle cells [252,253], cancer cells [54,254,255,256], and neurons [257].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [251]
In addition to AMPK activation, the mTOR-PI3K-MAPK axis is suppressed in response to mitochondrial uncoupling.
“In addition to AMPK activation (AMPKα1/α2 phosphorylation on Thr172), the mTOR-PI3K-MAPK axis is suppressed in response to mitochondrial uncoupling.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [251]

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Authors: Matejkova, O., Mustard, K. J., Sponarova, J., Flachs, P., Rossmeisl, M., Miksik, I., Thomason-Hughes, M., Grahame Hardie, D., & Kopecky, J.
Affiliations: University of Dundee (GB)
Czech Academy of Sciences (CZ)
ORCID: Sponarova, Jana
Rossmeisl, Martin
Venue: FEBS Letters
Publisher: Wiley
Published: 2004-06-15
Volume: 569
Issue: 1-3
Pages: 245-248
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/j.febslet.2004.06.002
OpenAlex: W2126160062
Cited by: 66
References: 39
Citations by year: 2026: 1 · 2024: 1 · 2023: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 5 · 2013: 1 · 2012: 4
FWCI: 3.96
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: AMPK, obesity resistance, white adipose tissue, adipocytes, adipogenic gene expression, lipid oxidation, transgenic mice
MeSH terms: Uncoupling Protein 1, Adenylate Kinase, Adipose Tissue, Animals, Base Sequence, Carrier Proteins, Epididymis, Immunity, Innate, Ion Channels, Male, Membrane Proteins, Mice, Inbred C57BL, Obesity, Oxidation-Reduction, Oxygen Consumption, Skin, DNA Primers, Oleic Acid, Reverse Transcriptase Polymerase Chain Reaction, Mitochondrial Proteins, Animals, Genetically Modified, Mice

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Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat

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