Induction of adipose and hepatic SWELL1 expression is required for maintaining systemic insulin-sensitivity in obesity

Litao Xie, Yanhui Zhang, Susheel K. Gunasekar, Anil Mishra, Lei Cao, Rajan Sah

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Obesity is associated with a loss of insulin-sensitivity and systemic dysglycemia, resulting in Type 2 diabetes, however the molecular mechanisms underlying this association are unclear. Through adipocyte patch-clamp studies, we recently showed that SWELL1 is required for the Volume-Regulated Anion Current (VRAC) in adipocytes and that SWELL1-mediated VRAC is activated by both mechanical and pathophysiological adipocyte expansion. We also demonstrated that adipocyte SWELL1 is required for maintaining insulin signaling and glucose homeostasis, particularly in the setting of obesity. Here we show that SWELL1 protein expression is induced in subcutaneous fat, visceral fat and liver in the setting of obesity. Long- term AAV/rec2-shRNA mediated SWELL1 knock-down in both fat and liver are associated with increased weight gain, increased adiposity and exacerbated insulin resistance in mice raised on a high-fat diet. These data further support the notion that SWELL1 induction occurs in insulin- sensitive tissues (liver and adipose) in the setting of over-nutrition and contributes to improved systemic glycemia by supporting enhanced insulin-sensitivity.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalChannels
Volume11
Issue number6
DOIs
StatePublished - Nov 2 2017

Keywords

  • LRRC8a
  • adeno-associated virus
  • adipocytes
  • channel
  • diabetes

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