A role for TRPV1 in influencing the onset of cardiovascular disease in obesity

Hypertension. 2013 Jan;61(1):246-52. doi: 10.1161/HYPERTENSIONAHA.112.201434. Epub 2012 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Blood Pressure / physiology
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Diet, High-Fat
  • Hypertension / complications
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Insulin Resistance
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Leptin / blood
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / complications
  • Obesity / genetics*
  • Obesity / metabolism
  • TRPV Cation Channels / genetics*
  • TRPV Cation Channels / metabolism

Substances

  • Blood Glucose
  • Interleukin-1beta
  • Leptin
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Interleukin-10