Effect of TRPV1 deletion on signs of metabolic syndrome in a high fat feeding study

Nichola Marshall1,2, Lihuan Liang1,2, Sarah-Jane Smillie1,2, Susan Brain1,2. 1Cardiovascular Division, King’s College London, London, United Kingdom, 2Centre for Integrative Biomedicine, King’s College London, London, United Kingdom.

It has recently been suggested that a role may exist for transient receptor potential vanilloid 1 (TRPV1) in obesity regulation. We have investigated for possible links between TRPV1 and signs of the metabolic syndrome through study of TRPV1 knockout (KO) mice. (1)(2) TRPV1 KO mice and their wildtype (WT) counterparts were fed either a high fat diet (35% fat by weight) or a normal diet (4% fat by weight) from 3 to 15 weeks of age, in studies performed in keeping with UK law. Weight was measured weekly. Blood pressure was measured by tail cuff plesmography and a glucose tolerance test was performed just before termination of experiment. Statistical analysis was by ANOVA plus Bonferroni’s post test.

Both WT and TRPV1 KO mice fed a high fat diet exhibited a similar significantly (p<0.001) higher end body weight (WT 34.0 ± 0.7g, mean ± s.e.m, n=11, TRPV1 KO 34.9 ± 1.8g, n=15) than mice fed a normal diet (WT 23.3 ± 0.7g, n=12, TRPV1 KO 23.6 ± 1.1g, n=14). No significant difference was observed between WT and TRPV1 KO high fat fed mice. Mean arterial pressure of WT mice fed a high fat diet was increased (p<0.01) compared with TRPV1 KO high fat fed mice and with WT and TRPV1KO normal fed mice. Analysis of aortae from WT high fat fed mice revealed that both aortic wall width and area were increased (p<0.01 and p<0.05 respectively) compared with other groups. In a similar manner kidney weights revealed that WT high fat fed mice had increased (p<0.01and p<0.001 respectively) kidney weight when compared with other groups. Finally a glucose tolerance test revealed that high fat fed mice exhibited impaired glucose handling but TRPV1 KO high fat fed mice showed significantly more ability to reverse the high plasma glucose levels than WT high (p<0.05).

These results suggest that TRPV1 KO mice are not resistant to diet-induced obesity, but do express a healthier phenotype in terms of markers of metabolic syndrome.

(1) Zhang et al, 2007, Circ Res 2007; 100:1063-1070.
(2) Gram & Hansen, 2007, Neuropeptides conference, Santorini 2007.

We thank the BHF and the BBSRC for support.