Background: Transient Receptor Potential Vanilloid 1 (TRPV1) channels in sensory
nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with
diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1
knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction.
Method: Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we
performed the intraperitoneal glucose tolerance test, measured the heart function through
transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac
histology, and measured the myocardial superoxide production and the expression of nicotinamide
adenine dinucleotide phosphate (NADPH) oxidases.
Results: HFD increased body weight, heart weight, and levels of fasting glucose, insulin, and leptin
in both strains, with no differences between two strains. HFD impaired glucose tolerance in both
strains with a more profound effect on Trpv1-/- than WT mice. HFD increased left ventricular (LV)
internal diameter in diastole in both strains, while increased LV posterior wall thickness in diastole
in Trpv1-/- but not in WT mice. HFD increased LV end-diastolic pressure in both strains with a
further increase in Trpv1-/- mice, while decreased -dP/dt in Trpv1-/- but not in WT mice. HFDinduced
cardiac collagen deposition and superoxide production were enhanced in Trpv1-/- mice.
HFD upregulated cardiac p22phox in both strains, while increased p47phox in Trpv1-/- but not in
Conclusion: In summary, TRPV1 knockout exacerbates HFD-induced glucose intolerance, cardiac
oxidative stress and collagen deposition, leading to aggravated LV diastolic dysfunction.