Cold exposure induces nuclear translocation of CRTC3 in brown adipose tissue
Abstract
In mammals, cold stress activates the cAMP-protein kinase A (PKA) signaling pathway, increases brown adipose tissue (BAT) activity, and induces thermogenesis to maintain body temperature. The cAMP responsive element binding protein (CREB)-regulated transcription coactivator 3 (CRTC3) plays important role in adipose development and energy metabolism. However, the effect of cold exposure on the intracellular localization of CRTC3 in BAT is unclear. Here, we report that cold-treated mice have higher expression of uncoupling protein 1 (UCP1) in adipose tissues and lower body weights and fat masses. Notably, cold exposure results in the nuclear translocation of CRTC3 in BAT. Moreover, forskolin (FSK), the activator of PKA pathway, induces the nuclear translocation of CRTC3 in brown adipocytes. At the molecular level, cold exposure and FSK treatment decrease liver kinase B1 (Lkb1) expression in brown adipocytes, which is related to the nuclear localization of CRTC3. These results demonstrate that the localization of CRTC3 involves in regulating cold-induced upregulation of UCP1 in BAT and provide useful information for understanding the molecular regulation of BAT thermogenesis induced by a cold environment.
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Cold induces Ucp1 expression in both humans and rodents, essentially by activating β-adrenergic receptors and the cAMP-dependent PKA signaling pathway.
“The most well-known condition to induce Ucp1 expression in both humans and rodents is cold, essentially by activating β-adrenergic receptors and the cAMP-dependent protein kinase (PKA)-dependent signaling pathway [38,39].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [38]
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- Authors
- Xu, Z., Liu, J., You, W., Wang, Y., & Shan, T.
- Affiliations
- Zhejiang University (CN)
- Corresponding author
- Shan, Tizhong
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2018-12-02
- Volume
- 120
- Issue
- 6
- Pages
- 9138-9146
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2902765963
- Cited by
- 23
- References
- 36
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 8 · 2020: 2 · 2019: 2
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31722053)
- Natural Science Foundation of Zhejiang Province (LR17C170001)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- CRTC3, nuclear translocation, brown adipose tissue, cold exposure, thermogenesis, cAMP/PKA signaling, UCP1, forskolin, LKB1, adipocytes, energy metabolism
- MeSH terms
- Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Cold Temperature, Mice, Inbred C57BL, Transcription Factors, Signal Transduction, Protein Transport, Active Transport, Cell Nucleus, Thermogenesis, Mice, Adipose Tissue, White
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