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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]
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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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