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Combined dipeptidyl peptidase-4 inhibitor with low-dose testosterone exerts greater efficacy than monotherapy on

Puntarik Keawtep1, Wasana Pratchayasakul1, Apiwan Arinno1

  • 1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.

Experimental Gerontology
|May 25, 2019
PubMed

Insights

Combined low-dose testosterone replacement therapy (TRT) and vildagliptin show promise for improving brain health and cognition in orchiectomized-obese rats. This combination therapy offers a potential therapeutic strategy for this complex condition.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Metabolic Syndrome

Background:

  • Obesity and orchiectomy independently contribute to brain pathologies and cognitive decline.
  • Existing treatments like testosterone replacement therapy (TRT) and vildagliptin show benefits in individual conditions but not in the combined orchiectomized-obese state.
  • High-dose TRT can mitigate brain defects but carries adverse effects, necessitating investigation into alternative therapeutic combinations.

Purpose of the Study:

  • To investigate the combined effects of low-dose TRT (1 mg/kg/day) and vildagliptin on brain function and cognitive performance in orchiectomized-obese rats.
  • To determine if this combination therapy can overcome the limitations of monotherapies in addressing neuroinflammation, oxidative stress, and cognitive deficits.

Main Methods:

  • Sixty male rats were fed either a normal diet (ND) or a high-fat diet (HFD) for 28 weeks.
  • Orchiectomy or sham-operation was performed at week 13.
  • At week 25, orchiectomized rats received vehicle, 2 mg/kg/day TRT, 3 mg/kg/day vildagliptin, or a combination of 1 mg/kg/day TRT and vildagliptin for 4 weeks.

Main Results:

  • Orchiectomy aggravated hippocampal oxidative stress, apoptosis, dendritic spine loss, microglial hyperactivity, and cognitive decline in HFD-fed rats.
  • While monotherapies partially ameliorated these brain pathologies in orchiectomized HFD-fed rats, the combined therapy demonstrated the most significant beneficial effects.
  • All tested treatments restored brain and cognitive functions in orchiectomized ND-fed rats.

Conclusions:

  • Combined low-dose TRT and vildagliptin therapy is a promising approach for restoring brain function and cognitive performance in orchiectomized-obese rats.
  • This combination therapy may offer a superior therapeutic strategy compared to monotherapies for addressing the complex neurobiological consequences of combined obesity and orchiectomy.
Keywords:
Cognitive functionDPP-4 inhibitorObese-insulin resistanceTestosterone deprivationTestosterone replacement therapy

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