Cited by 65Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismLipid metabolism and biosynthesis

Adipocyte-specific deficiency of Janus kinase (JAK) 2 in mice impairs lipolysis and increases body weight, and leads to insulin resistance with ageing

Shi, Sally Yu, Luk, Cynthia T., Brunt, Jara J., Sivasubramaniyam, Tharini, Lu, Shun-Yan, Schroer, Stephanie A., Woo, Minna·2014·Diabetologia

Abstract

Aims/hypothesis The growing obesity epidemic necessitates a better understanding of adipocyte biology and its role in metabolism. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediates signalling by numerous cytokines and hormones that regulate adipocyte function, illustrating the physiological importance of adipose JAK-STAT. The aim of this study was to investigate potential roles of adipocyte JAK2, an essential player in the JAK-STAT pathway, in adipocyte biology and metabolism. Methods We generated adipocyte-specific Jak2 knockout (A-Jak2 KO) mice using the Cre-loxP system with Cre expression driven by the Ap2 (also known as Fabp4) promoter. Results Starting at 2-3 months of age, male and female A-Jak2 KO mice gradually gained more body weight than control littermates primarily due to increased adiposity. This was associated with reduced energy expenditure in A-Jak2 KO mice. In perigonadal adipose tissue, the expression of numerous genes involved in lipid metabolism was differentially regulated. In addition, adipose tissue from A-Jak2 KO mice displayed impaired lipolysis in response to isoprenaline, growth hormone and leptin stimulation, suggesting that adipose JAK2 directly modulates the lipolytic program. Impaired lipid homeostasis was also associated with disrupted adipokine secretion. Accordingly, while glucose metabolism was normal at 2 months of age, by 5-6 months of age, A-Jak2 KO mice had whole-body insulin resistance. Concl…

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Crossref · 10.1007/s00125-014-3185-0

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Authors
Shi, S. Y., Luk, C. T., Brunt, J. J., Sivasubramaniyam, T., Lu, S.-Y., Schroer, S. A., & Woo, M.
Affiliations
  • MaRS (CA)
  • University of Toronto (CA)
  • University Health Network (CA)
Corresponding author
Woo, Minna
Venue
Diabetologia
Published
2014-02-16
Volume
57
Issue
5
Pages
1016-1026
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
OpenAlex
W2010232575
Cited by
61
References
45
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 10 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 6
FWCI
3.53
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (93707_1, MOP-81148)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
JAK2, adipocytes, JAK/STAT signaling, lipolysis, adiposity, obesity, insulin resistance, aging, energy expenditure, adipose tissue lipid metabolism, adipokine secretion, leptin, growth hormone, isoproterenol, type 2 diabetes
MeSH terms
Aging, Animals, Body Composition, Body Weight, Female, Glucose Tolerance Test, Insulin Resistance, Lipolysis, Male, Obesity, Promoter Regions, Genetic, Cytokines, Adipocytes, Mice, Knockout, Adiposity, Mice, Janus Kinase 2, Adipokines

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