Estrogen and DPP4 inhibitor, but not metformin, exert cardioprotection via attenuating cardiac mitochondrial dysfunction in obese insulin-resistant and estrogen-deprived female rats.
Cardiac function was markedly compromised in obese insulin-resistant and estrogen-deprived rats. Metformin and dipeptidyl peptidase-4 inhibitor (vildagliptin) were reported to improve cardiac function in insulin-resistant rats. Their effects on the heart under estrogen-deprived conditions are, however, unknown. Therefore, the effects of metformin, vildagliptin, and estrogen on the cardiac function in estrogen-deprived insulin-resistant female rats were investigated.



Bilateral ovariectomized female rats (n = 48) were divided to be fed with either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. Then, both ND- and HFD-fed groups were subdivided to receive a vehicle, estrogen (50 μg/kg), metformin (30 mg/kg), or vildagliptin (3 mg/kg) for 4 weeks (n = 6/group). Heart rate variability, echocardiography, metabolic and biochemical parameters, cardiac function, and mitochondrial function were determined. Sham-operated female rats (n = 6) were used as a control.



Both ND- and HFD-fed ovariectomized rats developed insulin resistance, depressed heart rate variability, and decreased cardiac contractility. Although treatment with metformin, vildagliptin, and estrogen improved metabolic status and cardiac function, only estrogen and vildagliptin improved diastolic blood pressure and left ventricular ±dP/dt, and also reduced mitochondrial impairment, apoptosis, and oxidative stress in HD-fed ovariectomized rats.



Treatment with estrogen and vildagliptin provided more beneficial effects in the inhibition of oxidative stress, apoptosis, and cardiac mitochondrial dysfunction, and preserved cardiac contractile performance in estrogen-deprived insulin-resistant female rats.
1Cardiac Electrophysiology Research and Training Center 2Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine 3Department of Oral Biology and Diagnostic Science, Faculty of Dentistry 4Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand 5School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand.
Sivaporn
S
Sivasinprasasn
Piangkwan
P
Sa-Nguanmoo
Wanpitak
W
Pongkan
Wasana
W
Pratchayasakul
Siriporn C
SC
Chattipakorn
Nipon
N
Chattipakorn
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D059305:Diet, High-Fat; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008594:Menopause, Premature / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000503:physiopathology; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077597:Vildagliptin
D002316:Cardiotonic Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004967:Estrogens; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane