Article Text

Download PDFPDF
P14 Protective effects arising from inhibition of TRPC1/5 ion channel permeation in hypercholesterolaemic mice
  1. B Rode,
  2. NY Yuldasheva,
  3. P Baxter,
  4. SB Wheatcroft,
  5. JF Ainscough,
  6. DJ Beech
  1. Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK


Transient Receptor Potential Canonical (TRPC) proteins assemble to form calcium-permeable non-selective cationic channels. We previously showed that TRPC1 and TRPC5 are expressed by adipocytes and that their inhibition increased the concentration of circulating adiponectin, which is an important anti-inflammatory and insulin-sensitising adipokine (Sukumar et al 2012, Circ Res 111, 191). The aim of this study was to investigate if the channels are relevant in hypercholesterolaemia. ApoE-knockout mice with conditional global expression of dominant-negative ion pore mutant TRPC5 (DNT5) were used to suppress ion permeation in the channels in vivo. Mice were fed with western-style diet and male litter-mates were compared with and without DNT5. Mice expressing DNT5 had significantly lower body weight compared to controls after 6 weeks and 12 weeks of treatment. Histological analysis showed significant reduction in adipocyte size. Quantitative RT-PC R analysis of adipose tissue showed that adiponectin mRNA was more abundant in the DNT5 group. By contrast, TNF-alpha and interleukin-6 mRNA were less abundant. No obvious adverse effects of DNT5 were evident. The data suggest that ion flux through heteromeric TRPC1/TRPC5 channels is a driver for weight gain, suppression of adiponectin gene expression and increased inflammation in hypercholesterolaemic mice. Therefore, inhibitors of the ion channels could be a strategy for protecting against obesity, insulin-resistance and inflammation.

Supported by the Medical Research Council

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.