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Cell Metab. 2016 Sep 13;24(3):420-433. doi: 10.1016/j.cmet.2016.08.005.

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals.

Author information

1
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Lilly Research Laboratories, Division of Eli Lilly and Company, Indianapolis, IN 46285, USA.
2
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100005, People's Republic of China.
3
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4
Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
5
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, 76 West Yanta Road, Xi'an, Shaanxi 710061, People's Republic of China.
6
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
7
Translational Physiology Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
8
Departments of Neuroscience and Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.
9
Departments of Pathology and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
10
Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
11
Lilly Research Laboratories, Division of Eli Lilly and Company, Indianapolis, IN 46285, USA.
12
Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: philipp.scherer@utsouthwestern.edu.

Abstract

"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.

KEYWORDS:

beiging; connexin 43; sympathetic signal; white adipose tissue

PMID:
27626200
PMCID:
PMC5024720
DOI:
10.1016/j.cmet.2016.08.005
[Indexed for MEDLINE]
Free PMC Article

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