Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals
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"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.
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Cell-to-cell communication via connexin 43 containing gap junctions is essential to disseminating adrenergic activation signals.
“Therefore, cell‐to‐cell communication via connexin 43 (CX43) containing gap junctions is essential to disseminating adrenergic activation signals 72.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [72]
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- Authors
- Zhu, Y., Gao, Y., Tao, C., Shao, M., Zhao, S., Huang, W., Yao, T., Johnson, J. A., Liu, T., Cypess, A. M., Gupta, O., Holland, W. L., Gupta, R. K., Spray, D. C., Tanowitz, H. B., Cao, L., Lynes, M. D., Tseng, Y.-H., Elmquist, J. K., Williams, K. W., Lin, H. V., & Scherer, P. E.
- Affiliations
- Eli Lilly (United States) (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- The University of Texas Southwestern Medical Center (US)
- The Ohio State University (US)
- National Institutes of Health (US)
- Albert Einstein College of Medicine (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Scherer, Philipp E.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 24
- Issue
- 3
- Pages
- 420-433
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5024720
- OpenAlex
- W2520032353
- Cited by
- 100
- References
- 51
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 12 · 2021: 17 · 2020: 7 · 2019: 12 · 2018: 9 · 2017: 9 · 2016: 2
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG041250)
- National Cancer Institute (R21CA178227, R01CA163640, R01CA166590)
- National Institute of Allergy and Infectious Diseases (R21AI124000)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK101865, P30DK041296, R01DK077097, R01DK102898, R01DK104789, F30DK108534, R01DK108833, R37DK053301, R01DK055758, R01DK088423, R01DK100699, P01DK088761, R01DK100659, T32DK007260, P30DK026687, P30DK036836, R01DK099110, P30DK020541, R00DK094973)
- National Institute of Neurological Disorders and Stroke (R01NS092466)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- connexin 43, beige adipocytes, electrical coupling, sympathetic innervation, proopiomelanocortin neurons, cold exposure, 18α-glycyrrhetinic acid, thermogenesis
- MeSH terms
- Adipose Tissue, Beige, Uncoupling Protein 1, Adaptation, Physiological, Animals, Adipose Tissue, Brown, Cold Temperature, Denervation, Glycyrrhetinic Acid, Mice, Inbred C57BL, Models, Biological, Neurons, Promoter Regions, Genetic, Sympathetic Nervous System, Signal Transduction, Gene Deletion, Gap Junctions, Connexin 43, Adipose Tissue, White
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