title: A role for TRPV1 in influencing the onset of cardiovascular disease in obesity.
abstract: Obesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat diet from 3 to 15 weeks. High-fat diet-fed mice from both genotypes became obese, with similar increases in body and adipose tissue weights. High-fat diet-fed TRPV1 knockout mice showed significantly improved handling of glucose compared with high-fat diet-fed wild-type mice. Hypertension, vascular hypertrophy, and altered nociception were observed in high-fat diet-fed wild-type but not high-fat diet-fed TRPV1 knockout mice. Wild-type, but not high-fat diet-fed TRPV1 knockout, mice demonstrated remodeling in terms of aortic vascular hypertrophy and increased heart and kidney weight, although resistance vessel responses were similar in each. Moreover, the wild-type mice had significantly increased plasma levels of leptin, interleukin 10 and interleukin 1β, whereas samples from TRPV1 knockout mice did not show significant increases. Our results do not support the concept that TRPV1 plays a major role in influencing weight gain. However, we identified a role of TRPV1 in the deleterious effects observed with high-fat feeding in terms of inducing hypertension, impairing thermal nociception sensitivity, and reducing glucose tolerance. The observation of raised levels of adipokines in wild-type but not TRPV1 knockout mice is in keeping with TRPV1 involvement in stimulating the proinflammatory network that is central to obesity-induced hypertension and sensory neuronal dysfunction.
authors.affiliation: British Heart Foundation Centre of Cardiovascular Excellence and Centre of Integrative Biomedicine, King’s College London, London, United Kingdom.
authors.forename: Nichola J
authors.initials: NJ
authors.lastname: Marshall
authors.forename: Lihuan
authors.initials: L
authors.lastname: Liang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bodkin
authors.forename: Cecile
authors.initials: C
authors.lastname: Dessapt-Baradez
authors.forename: Manasi
authors.initials: M
authors.lastname: Nandi
authors.forename: Sophie
authors.initials: S
authors.lastname: Collot-Teixeira
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Smillie
authors.forename: Kamal
authors.initials: K
authors.lastname: Lalgi
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Fernandes
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D020738:Leptin / Q000097:blood; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D053583:Interleukin-1beta; D020738:Leptin; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D016753:Interleukin-10