Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling
Open accessAbstract
Insulin and insulin-like growth factor 1 (IGF-1) have important roles in adipocyte differentiation, glucose tolerance and insulin sensitivity. Here to assess how these pathways can compensate for each other, we created mice with a double tissue-specific knockout of insulin and IGF-1 receptors to eliminate all insulin/IGF-1 signalling in fat. These FIGIRKO mice had markedly decreased white and brown fat mass and were completely resistant to high fat diet-induced obesity and age- and high fat diet-induced glucose intolerance. Energy expenditure was increased in FIGIRKO mice despite a >85% reduction in brown fat mass. However, FIGIRKO mice were unable to maintain body temperature when placed at 4 °C. Brown fat activity was markedly decreased in FIGIRKO mice but was responsive to β3-receptor stimulation. Thus, insulin/IGF-1 signalling has a crucial role in the control of brown and white fat development, and, when disrupted, leads to defective thermogenesis and a paradoxical increase in basal metabolic rate.
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WAT-specific insulin receptor deficiency was shown to protect mice from obesity, independently of food intake.
“Moreover, WAT-specific insulin receptor deficiency was shown to protect mice from obesity, independently of food intake [270,271].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [270]
The Discussion (page unavailable) says that fat-specific insulin receptor knockout (FIRKO) mice are protected against diet-induced obesity. The Results section, “Increased energy expenditure in FIGIRKO mice” (page unavailable), reports similar food intake only for mice lacking both the insulin and IGF-1 receptors in fat. It does not establish that food intake was unchanged in the insulin-receptor-only mice, and the knockout described is fat-specific rather than WAT-specific. (LLM, conf=0.88)
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- Authors
- Boucher, J., Mori, M. A., Lee, K. Y., Smyth, G., Liew, C. W., Macotela, Y., Rourk, M., Bluher, M., Russell, S. J., & Kahn, C. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Kahn, C. Ronald
- Venue
- Nature Communications
- Published
- 2012-06-12
- Volume
- 3
- Issue
- 1
- Pages
- 902-902
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3529640
- OpenAlex
- W2063114187
- Cited by
- 142
- References
- 41
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 12 · 2023: 6 · 2022: 18 · 2021: 11 · 2020: 11 · 2019: 2 · 2018: 9 · 2017: 15 · 2016: 12 · 2015: 12 · 2014: 14 · 2013: 10
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- American Diabetes Association
- Vanderbilt University (DK59637)
- Brandeis University
- Joslin Diabetes Center
- National Institutes of Health (DK-59637, DK31036, DK 36836)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, R01DK031036, DK34834, DK31036, DK59637, 5 P30 DK-36836, U24DK059637, DK82659, P30DK036836, R01DK082659)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- insulin signaling, IGF-1 signaling, insulin receptor, IGF-1 receptor, adipose tissue development, thermogenesis, brown adipose tissue, white adipose tissue, energy expenditure, impaired glucose tolerance, high-fat diet-induced obesity, thermoregulation, beta3-adrenergic receptor, adipogenesis, glucose homeostasis, tissue-specific knockout
- MeSH terms
- Adipose Tissue, Animals, Body Composition, Cells, Cultured, Energy Metabolism, Insulin, Insulin-Like Growth Factor I, Male, Temperature, Adipocytes, Mice, Knockout, Thermogenesis, Mice
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