P6283
Combined low-dose testosterone and dipeptidyl peptidase 4 inhibitor shared similar cardioprotective effects as therapeutic dose in obese-insulin resistant rats with testosterone deprivation

Extract

Background: Although several studies have shown that testosterone replacement therapy (TRT) exerted cardioprotective effects in obese subject with testosterone deprivation, some clinical studies reported the adverse effects of supraphysiological dose of TRT on the heart. According to this undesirable effect of TRT, dipeptidyl peptidase-4 inhibitor (DPP-4I) was reported as an alternative pharmacological intervention in obese-insulin resistant rats with testosterone deprivation. However, the effects of combined low-dose TRT and DPP-4I on left-ventricular (LV) function have never been investigated.

Purpose: We tested the hypothesis that combined low-dose TRT and DPP-4I therapy exerts higher efficacy than either single regimen in improving metabolic parameters and LV function via the better attenuation of cardiac mitochondrial dysfunction and apoptosis in obese-insulin resistant rats with testosterone deprivation.

Methods: Male Wistar rats were fed with either normal diet (ND) or high-fat diet (HFD) for 12 weeks. Then, rats in each dietary group were subdivided into 2 operation groups; sham operation (NDS, HFS; n=6/group) and orchiectomy (NDO and HFO). After 12 weeks of operation, NDO and HFO rats were subdivided into 4 treatment groups (n=6/group) including 1) vehicle (NDOV, HFOV), 2) TRT (2 mg/kg/d), 3) DPP-4I (vildagliptin, 3 mg/kg/d), 4) combined low-dose TRT and DPP-4I (1 mg/kg/d-TRT + 3 mg/kg/d-vildagliptin). Rats were received their assigned treatment for 4 weeks. Metabolic parameters, LV function, cardiac mitochondrial function, and apoptosis were determined.