2. Academic Validation
  3. Schwann cell-specific Pten inactivation reveals essential role of the sympathetic nervous system activity in adipose tissue development

Schwann cell-specific Pten inactivation reveals essential role of the sympathetic nervous system activity in adipose tissue development

  • Biochem Biophys Res Commun. 2020 Oct 15;531(2):118-124. doi: 10.1016/j.bbrc.2020.07.050.
Xiao-Xiao Li 1,  Shi-Jie Zhang 2,  Ka-Yi Man 1,  Amy P Chiu 1,  Lilian H Lo 1,  Jeffrey C To 1,  Cynthia H Chiu 1,  Chi-On Chan 1,  Daniel K W Mok 1,  Dewi K Rowlands 3,  Vincent W Keng 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
  • 2 State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong; Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Laboratory Animal Services Centre, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong.
  • 4 State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address: vincent.keng@polyu.edu.hk.
PMID: 32782145 DOI: 10.1016/j.bbrc.2020.07.050
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

Pten; Schwann cell; Sympathetic nervous system; White adipose tissue.

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