Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice
Open accessAbstract
C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a β 3 -adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice.
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In rodents, small collections of physiologically relevant BAT have been found in the hindlimb in intermuscular adipose tissue and mixed with white fat.
“In rodents, small collections of physiologically relevant BAT have been found in the hindlimb in intermuscular adipose tissue and mixed with white fat 86,87.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [86]
Systemic brown adipocytes are often found admixed with white fat cells; are more sensitive to β3-adrenergic stimulation and cold exposure; and their thermogenic capacity appears to be regulated by genetic background.
“These systemic brown adipocytes are often found admixed with white fat cells; are more sensitive to β3-adrenergic stimulation and cold exposure; and their thermogenic capacity appears to be regulated by genetic background 86,87,74.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [86]
Brown adipocytes interspersed between muscle bundles in mice have been identified.
“However, the recent identification of brown adipocytes interspersed between muscle bundles in mice 86 opens up the question whether some of the measured NST energy expenditure in skeletal muscle comes from these interspersed brown adipocytes.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [86]
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- Authors
- Almind, K., Manieri, M., Sivitz, W. I., Cinti, S., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Institute of Normal Human Morphology and Anatomy, University of Ancona, 6013 Ancona, Italy; and
- University of Iowa (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-02-13
- Volume
- 104
- Issue
- 7
- Pages
- 2366-2371
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1892979
- OpenAlex
- W2038657829
- Cited by
- 286
- References
- 43
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 7 · 2018: 16 · 2017: 17 · 2016: 11 · 2015: 18 · 2014: 21 · 2013: 35 · 2012: 20
- FWCI
- 16.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- National Institutes of Health (DK31036)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, DK 30136, R01DK031036, DK45935, DK-60837, R01DK045935, R01DK060837)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- intermuscular fat, UCP1, metabolic syndrome, high-fat diet, obesity, insulin resistance, hyperglycemia, energy expenditure, beta3-adrenergic agonists, brown adipocytes, C57BL/6 mice, strain differences, mitochondrial uncoupling
- MeSH terms
- Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Dietary Fats, Energy Metabolism, Ion Channels, Mice, Inbred C57BL, Mice, Inbred Strains, Mitochondria, Muscles, Risk, Weight Gain, Up-Regulation, Mitochondrial Proteins, Metabolic Syndrome, Mice
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