Abstract
BackgroundObesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1−/−) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia-reperfusion (I/R) injury.MethodsTRPV1−/− and wild-type (WT) mice were fed a chow or Western diet (WD) for 22–23 weeks. After that, mice were subjected to renal I/R injury, and renal cortical blood flow (CBF) and medullary blood flow (MBF) were measured.ResultsThe Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1−/− and WT mice. WD-induced impairment of glucose tolerance was worsened in TRPV1−/− mice compared with WT mice. WD intake prolonged the time required to reach peak reperfusion in the cortex and medulla (both P < 0.05), decreased the recovery rate of CBF (P < 0.05) and MBF (P < 0.05), and increased blood urea nitrogen, plasma creatinine, and urinary 8-isoprostane levels after I/R in both mouse strains, with greater effects in TRPV1−/− mice (all P < 0.05). Renal I/R increased calcitonin gene-related peptide (CGRP) release in WT but not in TRPV1−/− mice, and WD attenuated CGRP release in WT mice. Moreover, blockade of CGRP receptors impaired renal regional blood flow and renal function in renal I/R injured WT mice.ConclusionThese results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow.
Highlights
Obesity is a major risk factor for diabetes and hypertension (Hall, 2003; Steinberger & Daniels, 2003), which together account for 70% of all cases of end-stage renal disease (Collins et al, 2005; Griffin, Kramer & Bidani, 2008)
Knockout of Transient receptor potential vanilloid 1 (TRPV1) exacerbated Western diet (WD)-induced glucose intolerance and oxidative stress At 23 weeks, WD intake increased body weight in both WT and TRPV1-/- mice when compared with chow diet groups, there were no differences between WT and TRPV1-/- mice fed with either chow or WD (Fig. 1A)
Knockout of TRPV1 exacerbated WD-induced impairment of renal blood flow recovery After I/R, TRPV1-/- mice on chow diet had significantly decreased recovery rates of cortical blood flow (CBF) and medullary blood flow (MBF) and increased time to peak reperfusion compared with WT mice on chow
Summary
Obesity is a major risk factor for diabetes and hypertension (Hall, 2003; Steinberger & Daniels, 2003), which together account for 70% of all cases of end-stage renal disease (Collins et al, 2005; Griffin, Kramer & Bidani, 2008). TRPV1 protects renal ischemia-reperfusion injury in diet-induced obese mice by enhancing CGRP release and increasing renal blood flow. Western diet (WD) intake leads to obesity, aggravates chronic inflammation, and enhances acute renal ischemic injury (Kelly, Burford & Dominguez, 2009). Using transient receptor potential vanilloid 1 knockout (TRPV1-/-) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia-reperfusion (I/R) injury. Results: The Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1-/- and WT mice. Conclusion: These results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow
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