Adipose-specific disruption of signal transducer and activator of transcription 3 increases body weight and adiposity
Open accessAbstract
To determine the role of STAT3 in adipose tissue, we used Cre-loxP DNA recombination to create mice with an adipocyte-specific disruption of the STAT3 gene (ASKO mice). aP2-Cre-driven disappearance of STAT3 expression occurred on d 6 of adipogenesis, a time point when preadipocytes have already undergone conversion to adipocytes. Thus, this knockout model examined the role of STAT3 in mature but not differentiating adipocytes. Beginning at 9 wk of age, ASKO mice weighed more than their littermate controls and had increased adipose tissue mass, associated with adipocyte hypertrophy, but not adipocyte hyperplasia, hyperphagia, or reduced energy expenditure. Leptin-induced, but not isoproterenol-induced, lipolysis was impaired in ASKO adipocytes, which may partially explain the increased cell size. Despite reduced adiponectin and increased liver triacylglycerol, ASKO mice displayed normal glucose tolerance. Overall, these findings demonstrate that adipocyte STAT3 regulates body weight homeostasis in part through direct effects of leptin on adipocytes.
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Adipocyte-specific Stat3-KO mice have increased body weight and more adipose tissue mass due to adipocyte hypertrophy, without evidence of adipocyte hyperplasia, hyperphagia, or reduced energy expenditure.
“Adipocyte-specific Stat3-KO mice have increased body weight and more adipose tissue mass due to adipocyte hypertrophy, but do not show evidence of adipocyte hyperplasia, hyperphagia, or reduced energy expenditure (Cernkovich et al., 2008), suggesting a role of STAT3 in lipolysis.”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Cernkovich et al., 2008
The Discussion reports increased body weight and adiposity associated with adipocyte hypertrophy, not hyperplasia, hyperphagia, or reduced energy expenditure, in male ASKO mice fed standard chow. The claim omits that restriction: the Results report normal growth curves in female ASKO mice. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAdipocyte-specific STAT3 knockout increases body weight and adiposity.
“Increased body weight and adiposity”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Cernkovich et al., 2008
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“Adipocyte-specific Stat3-KO mice have increased body weight and more adipose tissue mass due to adipocyte hypertrophy, but do not show evidence of adipocyte hyperplasia, hyperphagia, or reduced energy expenditure (Cernkovich et al., 2008), suggesting a role”
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A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods
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JAK-STAT in Lipid Metabolism of Adipocytes
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- Authors
- Cernkovich, E. R., Deng, J., Bond, M. C., Combs, T. P., & Harp, J. B.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Harp, Joyce B.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-12-20
- Volume
- 149
- Issue
- 4
- Pages
- 1581-1590
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2276706
- OpenAlex
- W1979647427
- Cited by
- 87
- References
- 6
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 11 · 2012: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk053398-04)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-59337, T32DK007686, DK 34987, R01DK059337, DK56350, DK 53398, DK07686, P30DK034987, P30DK056350)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- STAT3, adipose tissue, adipocyte-specific knockout, adipocyte hypertrophy, body weight homeostasis, leptin signaling, lipolysis, adiponectin, liver triacylglycerol, glucose tolerance, adipogenesis, energy expenditure
- MeSH terms
- Animals, Body Weight, Eating, Energy Metabolism, Female, Liver, Male, Mice, Inbred C57BL, Triglycerides, Signal Transduction, Adipocytes, Mice, Knockout, Leptin, Adiposity, STAT3 Transcription Factor, Mice
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