Cited by 44Adipose Tissue and MetabolismMetabolism, Diabetes, and CancerMitochondrial Function and Pathology

Augmenting energy expenditure by mitochondrial uncoupling: A role of AMP-activated protein kinase

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Klaus, Susanne, Keipert, Susanne, Rossmeisl, Martin, Kopecky, Jan·2012·Genes & Nutrition

Abstract

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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  1. Himms-Hagen J (1983) Role of thermogenesis in brown adipose tissue in the regulation of energy balance. In: Hollenberg CH, Roncardi DAK (eds) The adipose and obesity: cellular and molecular mechanisms. Raven Press, New York, pp 259-270

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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
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
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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