Augmenting energy expenditure by mitochondrial uncoupling: A role of AMP-activated protein kinase
Open accessAbstract
Strategies to prevent and treat obesity aim to decrease energy intake and/or increase energy expenditure. Regarding the increase of energy expenditure, two key intracellular targets may be considered (1) mitochondrial oxidative phosphorylation, the major site of ATP production, and (2) AMP-activated protein kinase (AMPK), the master regulator of cellular energy homeostasis. Experiments performed mainly in transgenic mice revealed a possibility to ameliorate obesity and associated disorders by mitochondrial uncoupling in metabolically relevant tissues, especially in white adipose tissue (WAT), skeletal muscle (SM), and liver. Thus, ectopic expression of brown fat-specific mitochondrial uncoupling protein 1 (UCP1) elicited major metabolic effects both at the cellular/tissue level and at the whole-body level. In addition to expected increases in energy expenditure, surprisingly complex phenotypic effects were detected. The consequences of mitochondrial uncoupling in WAT and SM are not identical, showing robust and stable obesity resistance accompanied by improvement of lipid metabolism in the case of ectopic UCP1 in WAT, while preservation of insulin sensitivity in the context of high-fat feeding represents the major outcome of muscle UCP1 expression. These complex responses could be largely explained by tissue-specific activation of AMPK, triggered by a depression of cellular energy charge. Experimental data support the idea that (1) while being always activated in response to mitochondrial uncoupling and compromised intracellular energy status in general, AMPK could augment energy expenditure and mediate local as well as whole-body effects; and (2) activation of AMPK alone does not lead to induction of energy expenditure and weight reduction.
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The effects of UCP-1 overexpression are fat depot-dependent and can be explained by differences in AMPK subunit activation.
“Interestingly, the effects of UCP-1 overexpression are fat depot-dependent and can be explained by differences in term of AMPK subunit activation (reviewed here [258]).”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [258]
Specific overexpression of UCP-1 in white adipocytes (aP2-UCP-1 mice) activates AMPK in this cell type.
“Specific overexpression of UCP-1 in white adipocytes (aP2-UCP-1 mice) also activates AMPK in this cell type.”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [258]
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Flagged first, then by citations
Research works printed but not linked: 1
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- Authors
- Klaus, S., Keipert, S., Rossmeisl, M., & Kopecky, J.
- Affiliations
- German Institute of Human Nutrition (DE)
- Czech Academy of Sciences (CZ)
- Venue
- Genes & Nutrition
- Published
- 2011-12-04
- Volume
- 7
- Issue
- 3
- Pages
- 369-386
- ISSN
- 1555-8932 (ISSN-L)
- 1865-3499
- PMC
- PMC3380193
- OpenAlex
- W2032910880
- Cited by
- 44
- References
- 118
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 5
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Genes & Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ASEP (submittedVersion, public-domain)
- Funders
- European Commission (244995, 2007–2013, FP7 2007-2013)
- Deutsche Forschungsgemeinschaft
- Ministerstvo Zdravotnictví Ceské Republiky
- 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 › Mitochondrial Function and Pathology
- Keywords
- mitochondrial uncoupling, AMPK, energy expenditure, obesity, UCP1, brown adipose tissue, white adipose tissue, skeletal muscle, liver, cellular energy homeostasis, insulin sensitivity, lipid metabolism, high-fat feeding, transgenic mice
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