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Title: Schwann cell-specific Pten inactivation reveals essential role of the sympathetic nervous system activity in adipose tissue development
Authors: Li, XX 
Zhang, SJ 
Man, KY 
Chiu, AP 
Lo, LH 
To, JC 
Chiu, CH 
Chan, CO 
Mok, DKW 
Rowlands, DK
Keng, VW 
Issue Date: 15-Oct-2020
Source: Biochemical and biophysical research communications, 15 October 2020, v. 531, no. 2, p. 118-124
Abstract: There is increasing evidence that the sympathetic nervous system (SNS) plays an important role in adipose tissue development. However, the underlying molecular mechanism(s) associated with this remains unclear. SNS innervation of white adipose tissue (WAT) is believed to be necessary and sufficient to elicit WAT lipolysis. In this current study, mice with Schwann cell (SC)-specific inactivation of phosphatase and tensin homolog (Pten) displayed enlarged inguinal white adipose tissue (iWAT). This serendipitous observation implicates the role of SCs in mediating SNS activity associated with mouse adipose tissue development. Mice with SC-specific Pten inactivation displayed enlarged iWAT. Interestingly, the SNS activity in iWAT of SC-specific Pten-deficient mice was reduced as demonstrated by decreased tyrosine hydroxylase (TH) expression level and neurotransmitters, such as norepinephrine (NE) and histamine (H). The lipolysis related protein, phosphorylated hormone sensitive lipase (pHSL), was also decreased. As expected, AKT-associated signaling pathway was hyperactivated and hypothesized to induce enlarged iWAT in SC-specific Pten-deficient mice. Moreover, preliminary experiments using AKT inhibitor AZD5363 treatment ameliorated the enlarged iWAT condition in SC-specific Pten-deficient mice. Taken together, SCs play an essential role in the regulation of SNS activity in iWAT development via the AKT signaling pathway. This novel role of SCs in SNS function allows for better understanding into the genetic mechanisms of peripheral neuropathy associated obesity.
Keywords: Sympathetic nervous system
Schwann cell
White adipose tissue
Publisher: Elsevier
Journal: Biochemical and biophysical research communications 
ISSN: 0006-291X
EISSN: 1090-2104
DOI: 10.1016/j.bbrc.2020.07.050
Rights: ©2020 Elsevier Inc. All rights reserved.
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