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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 86,87.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [86]
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“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]
In the citing paper
“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]
Citations
Cites
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
Obesity and the regulation of energy balance
Spiegelman, B. M., & Flier, J. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00240-9 · Cited by 2,398
Towards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630
Thermogenic mechanisms in brown fat.
Nicholls, D. G., & Locke, R. M. (1984) · Physiological Reviews · doi:10.1152/physrev.1984.64.1.1 · Cited by 1,602
Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
Enerbäck, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M.-E., & Kozak, L. P. (1997) · Nature · doi:10.1038/387090a0 · Cited by 1,379
Reduced Rate of Energy Expenditure as a Risk Factor for Body-Weight Gain
Ravussin, E., Lillioja, S., Knowler, W. C., Christin, L., Freymond, D., Abbott, W. G. H., Boyce, V., Howard, B. V., & Bogardus, C. (1988) · New England Journal of Medicine · doi:10.1056/nejm198802253180802 · Cited by 1,215
Development of obesity in transgenic mice after genetic ablation of brown adipose tissue
Lowell, B. B., S-Susulic, V., Hamann, A., Lawitts, J. A., Himms-Hagen, J., Boyer, B. B., Kozak, L. P., & Flier, J. S. (1993) · Nature · doi:10.1038/366740a0 · Cited by 1,075
Hotamışlıgil, G. S., Johnson, R. S., Distel, R. J., Ellis, R., Papaioannou, V. E., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.274.5291.1377 · Cited by 915
Parental transmission of type 2 diabetes: the Framingham Offspring Study
Meigs, J. B., Cupples, L. A., & Wilson, P. W. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2201 · Cited by 666
Guerra, C., Koza, R. A., Yamashita, H., Walsh, K., & Kozak, L. P. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3155 · Cited by 635
The Biology of Mitochondrial Uncoupling Proteins
Rousset, S., Alves‐Guerra, M., Mozo, J., Miroux, B., Cassard, A., Bouillaud, F., & Ricquier, D. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s130 · Cited by 560
Targeted Disruption of the β3-Adrenergic Receptor Gene
Susulic, V. S., Frederich, R. C., Lawitts, J. A., Tozzo, E., Kahn, B. B., Harper, M., Himms‐Hagen, J., Flier, J. S., & Lowell, B. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29483 · Cited by 493
Nuclear receptor corepressor RIP140 regulates fat accumulation
Leonardsson, G., Steel, J. H., Christian, M., Pocock, V., Milligan, S., Bell, J., So, P.-W., Medina-Gomez, G., Vidal-Puig, A., White, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401013101 · Cited by 366
Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice
Surwit, R. S., Wang, S., Petro, A. E., Sanchı́s, D., Raimbault, S., Ricquier, D., & Collins, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.4061 · Cited by 311
LXRs regulate the balance between fat storage and oxidation
Kalaany, N. Y., Gauthier, K. C., Zavacki, A. M., Mammen, P. P. A., Kitazume, T., Peterson, J. A., Horton, J. D., Garry, D. J., Bianco, A. C., & Mangelsdorf, D. J. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.03.001 · Cited by 309
Dietary fat, genetic predisposition, and obesity: lessons from animal models
West, D., & York, B. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/67.3.505s · Cited by 291
Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice
Li, B., Nolte, L. A., Ju, J.-S., Ho Han, D., Coleman, T., Holloszy, J. O., & Semenkovich, C. F. (2000) · Nature Medicine · doi:10.1038/80450 · Cited by 291
Variation in Type 2 Diabetes-Related Traits in Mouse Strains Susceptible to Diet-Induced Obesity
Rossmeisl, M., Rim, J. S., Koza, R. A., & Kozak, L. P. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1958 · Cited by 288
Genetic Determinants of Energy Expenditure and Insulin Resistance in Diet-Induced Obesity in Mice
Almind, K., & Kahn, C. R. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3274 · Cited by 254
Self-citationDalgaard, L. T., & Pedersen, O. B. (2001) · Diabetologia · doi:10.1007/s001250100596 · Cited by 214
Lee, E. T., Howard, B. V., Savage, P. J., Cowan, L. D., Fabsitz, R. R., Oopik, A. J., Yeh, J. L., Go, O. T., Robbins, D. C., & Welty, T. K. (1995) · Diabetes Care · doi:10.2337/diacare.18.5.599 · Cited by 212
Xue, B., Coulter, A. A., Rim, J. S., Koza, R. A., & Kozak, L. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.18.8311-8322.2005 · Cited by 179
The brown adipocyte: update on its metabolic role
Sell, H., Deshaies, Y., & Richard, D. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.04.003 · Cited by 168
Yechoor, V. K., Patti, M.-E., Saccone, R., & Kahn, C. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142301999 · Cited by 156
Self-citationAnalysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans.
Garruti, G., & Ricquier, D. (1992) · PubMed · Cited by 144
The role of uncoupling proteins in the regulation of metabolism
Erlanson‐Albertsson, C. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01159.x · Cited by 123
Kulkarni, R., Almind, K., Goren, H. J., Winnay, J. N., Ueki, K., Okada, T., & Kahn, C. R. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1528 · Cited by 116
Self-citationNutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice
Bachmanov, A. A., Reed, D. R., Tordoff, M. G., Price, R. A., & Beauchamp, G. K. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00412-7 · Cited by 107
Hong, Y., Fink, B. D., Dillon, J. S., & Sivitz, W. I. (2001) · Endocrinology · doi:10.1210/endo.142.1.7889 · Cited by 107
Self-citationCinti, S., Cancello, R., Zingaretti, M. C., Ceresi, E., Matteis, R. D., Giordano, A., Himms‐Hagen, J., & Ricquier, D. (2002) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540205000103 · Cited by 84
Self-citationM ETABOLIC L ESSONS FROM G ENETICALLY L EAN M ICE
Reitman, M. L. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.010402.102849 · Cited by 75
UCP2-dependent Proton Leak in Isolated Mammalian Mitochondria
Fink, B. D., Hong, Y.-S., Mathahs, M. M., SCHOLZ, T. D., Dillon, J. S., & Sivitz, W. I. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107955200 · Cited by 74
Self-citationThe role of motor activity in diet-induced obesity in C57BL/6J mice
Brownlow, B. S., Petro, A. E., Feinglos, M. N., & Surwit, R. S. (1996) · Physiology & Behavior · doi:10.1016/0031-9384(95)02210-4 · Cited by 72
Immunohistochemical detection of human brown adipose tissue uncoupling protein in an autopsy series.
Kortelainen, M. ‐., Pelletier, G., Ricquier, D., & Bukowiecki, L. J. (1993) · Journal of Histochemistry & Cytochemistry · doi:10.1177/41.5.8468458 · Cited by 71
Coulter, A. A., Bearden, C. M., Liu, X., Koza, R. A., & Kozak, L. P. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00057.2003 · Cited by 62
Almind, K., Kulkarni, R., Lannon, S. M., & Kahn, C. R. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1535 · Cited by 53
Self-citationOpposite Effects of Background Genotype on Muscle and Liver Insulin Sensitivity of Lipoatrophic Mice
Colombo, C., Haluzı́k, M., Cutson, J. J., Dietz, K. R., Marcus‐Samuels, B., Vinson, C., Gavrilova, O., & Reitman, M. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207665200 · Cited by 51
Does Brown Adipose Tissue (BAT) Have a Role in the Physiology or Treatment of Human Obesity?
Himms‐Hagen, J. (2001) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1011856617047 · Cited by 45
Insulin Resistance in the Pathogenesis of NIDDM in Pima Indians
Bogardus, C. (1993) · Diabetes Care · doi:10.2337/diacare.16.1.228 · Cited by 39
Adaptive thermogenesis: Turning on the heat
Lowell, B. B. (1998) · Current Biology · doi:10.1016/s0960-9822(07)00336-3 · Cited by 34
Adiposity and the Development of Diabetes in Mouse Genetic Models
Kozak, L. P., & Rossmeisl, M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04266.x · Cited by 21
The Uncoupling Proteins UCP2 and UCP3 in Skeletal Muscle
Wolf, G. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.2001.tb06977.x · Cited by 9
Research works printed but not linked: 1
- G Garruti, D Ricquier Int J Obes Relat Metab Disord 16, 383–390 (1992).
Cited by
Sorted by citations
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399
Self-citationPRDM16 controls a brown fat/skeletal muscle switch
Seale, P., Bjork, B., Yang, W., Kajimura, S., Chin, S., Kuang, S., Scimè, A., Devarakonda, S., Conroe, H. M., Erdjument-Bromage, H., et al. (2008) · Nature · doi:10.1038/nature07182 · Cited by 2,347
Developmental Origin of Fat: Tracking Obesity to Its Source
Gesta, S., Tseng, Y.-H., & Kahn, C. R. (2007) · Cell · doi:10.1016/j.cell.2007.10.004 · Cited by 1,508
Self-citationMitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341
Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263
Metadata
- 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 (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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