The DOI matches its Crossref record; 94 of the 99 references it cites were found in a registry or an index.
Nonshivering thermogenesis and its adequate measurement in metabolic studies
Open accessAbstract
Alterations in nonshivering thermogenesis are presently discussed as being both potentially causative of and able to counteract obesity. However, the necessity for mammals to defend their body temperature means that the ambient temperature profoundly affects the outcome and interpretation of metabolic experiments. An adequate understanding and assessment of nonshivering thermogenesis is therefore paramount for metabolic studies. Classical nonshivering thermogenesis is facultative, i.e. it is only activated when an animal acutely requires extra heat (switched on in minutes), and adaptive, i.e. it takes weeks for an increase in capacity to develop. Nonshivering thermogenesis is fully due to brown adipose tissue activity; adaptation corresponds to the recruitment of this tissue. Diet-induced thermogenesis is probably also facultative and adaptive and due to brown adipose tissue activity. Although all mammals respond to injected/infused norepinephrine (noradrenaline) with an increase in metabolism, in non-adapted mammals this increase mainly represents the response of organs not involved in nonshivering thermogenesis; only the increase after adaptation represents nonshivering thermogenesis. Thermogenesis (metabolism) should be expressed per animal, and not per body mass [not even to any power (0.75 or 0.66)]. A 'cold tolerance test' does not examine nonshivering thermogenesis capacity; rather it tests shivering capacity and endurance. For mice, normal animal house temperatures are markedly below thermoneutrality, and the mice therefore have a metabolic rate and food consumption about 1.5 times higher than their intrinsic requirements. Housing and examining mice at normal house temperatures carries a high risk of identifying false positives for intrinsic metabolic changes; in particular, mutations/treatments that affect the animal's insulation (fur, skin) may lead to such problems. Correspondingly, true alterations in intrinsic metabolic rate remain undetected when metabolism is examined at temperatures below thermoneutrality. Thus, experiments with animals kept and examined at thermoneutrality are likely to yield an improved possibility of identifying agents and genes important for human energy balance.
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“Animal models have shown that GLP-1 can increase energy expenditure and regulate heat production and conversion from white adipose tissue to brown adipose tissue in obese mice [42], although human data on this effect are not yet convincing [18,43].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [42]
Citations
Cites
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Unexpected evidence for active brown adipose tissue in adult humans
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00691.2006 · Cited by 1,824
Self-citationA role for brown adipose tissue in diet-induced thermogenesis
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The menthol receptor TRPM8 is the principal detector of environmental cold
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Self-citationLoss of stearoyl–CoA desaturase-1 function protects mice against adiposity
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Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat
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Cited by
Sorted by citations
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
“In mice, acute central (i.c.v.) but not peripheral administration of GLP-1 increased brown adipose tissue (BAT) temperature and increased the activity of sympathetic fibers that innervate the inguinal BAT [773].”
BackgroundInfluentialFGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478
“2A,B), which is indicative of enhanced shivering (Cannon and Nedergaard 2011).”
BackgroundSarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies
Batsis, J. A., & Villareal, D. T. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0062-9 · Cited by 1,382
Fever and the thermal regulation of immunity: the immune system feels the heat
Evans, S. S., Repasky, E. A., & Fisher, D. T. (2015) · Nature reviews. Immunology · doi:10.1038/nri3843 · Cited by 1,312
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
Nguyen, K. D., Qiu, Y., Cui, X., Goh, Y. P. S., Mwangi, J., David, T., Mukundan, L., Brombacher, F., Locksley, R. M., & Chawla, A. (2011) · Nature · doi:10.1038/nature10653 · Cited by 1,038
Metadata
- Authors
- Cannon, B., & Nedergaard, J.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Cannon, Barbara
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2011-01-15
- Volume
- 214
- Issue
- 2
- Pages
- 242-253
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- OpenAlex
- W2148400263
- Cited by
- 677
- References
- 99
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 32 · 2023: 45 · 2022: 42 · 2021: 55 · 2020: 53 · 2019: 42 · 2018: 69 · 2017: 48 · 2016: 47 · 2015: 42 · 2014: 48 · 2013: 48 · 2012: 41
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Journal of Experimental Biology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Physical Sciences › Environmental Science › Ecology › Physiological and biochemical adaptations
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- non-shivering thermogenesis, brown adipose tissue, thermoneutrality, ambient temperature, metabolic rate measurement, norepinephrine, shivering, diet-induced thermogenesis, obesity, energy balance, mice, fur insulation
- MeSH terms
- Acclimatization, Animals, Adipose Tissue, Brown, Cold Temperature, Humans, Norepinephrine, Thermogenesis
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