Impact of TRPC channels on body weight (1057.9)

Abstract

We previously showed that Transient Receptor Potential Canonical (TRPC) channels are expressed by adipocytes and that short‐term inhibition of these channels increased the concentration of circulating adiponectin, suggesting a functional role of TRPC channels in adipocyte biology in vivo (Sukumar et al, Circ Res. 2012;111:191‐200). The aim of this study was to investigate if there are implications of TRPC channels for the control of body weight. Mice with conditional global expression of dominant‐negative ion pore mutant TRPC5 were used to suppress ion permeation in TRPC channels in vivo in adults without deleting TRPC proteins. Mice were fed a western‐style high fat diet for 12 weeks and male litter‐mates were compared with and without suppression of TRPC ion permeation. Mice expressing mutant TRPC5 showed significantly lower body weight as compared to controls. No obvious adverse effects on health were evident. Analysis of adipose tissue showed that adiponectin mRNA was more abundant in the mice expressing mutant TRPC5, suggesting regulation of gene expression in adipocytes. The results suggest that ion flux through TRPC channels is a driver for weight gain and that ion pore blockers of TRPC channels could be an approach for protecting against obesity.Grant Funding Source: Supported by the Medical Research Council