Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation.
OBJECTIVE
The biochemical and structural cardiac oxidative-dependent damage induced by high-fat (HF) diet was examined in a rabbit model, together with the role of dehydroepiandrosterone (DHEA) in contrasting tissue damage.


METHODS
New Zealand white rabbits fed a HF diet supplemented or not with DHEA (0.02%) were utilized for 12 weeks. Oxidative stress, inflammatory and necrosis parameters, fatty deposition, heavy-chain myosin isoforms (MHC) expression and papillary muscle functionality were examined in the left ventricle of rabbits.


RESULTS
Rabbits fed a HF diet that showed hyperglycemia, insulin resistance and dyslipidemia together with increase of oxidative stress and of advanced end-glycation product levels have been observed. Concerning pro-inflammatory insults, there was increased p65-NFkB activation and increased tumor necrosis factor-alpha and C-reactive protein expressions. Cellular damage induced by the HF diet was detected through the switch of expression of MHC isoforms, indicating impairment of cardiac contractility, confirmed by altered of basal parameters of papillary muscle functionality. Rabbits fed the HF diet supplemented with DHEA showed a partial reduction of oxidative stress and the inflammatory state. Cardiac necrosis, the shift of MHC isoforms, and cardiac functionality, were also partially counteracted.


CONCLUSIONS
Rabbits fed with a HF diet showed a beneficial effect when low-dose DHEA was added to the diet. The steroid, without affecting high plasma glucose level or insulin resistance, restored oxidative balance, lowered lipid levels and inflammation insults, preventing cellular and functional alterations of cardiac tissue and thus delaying the onset of cardiac damage.
Aragno
M
M
Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, Turin, Italy. manuela.aragno@unito.it
Meineri
G
G
Vercellinatto
I
I
Bardini
P
P
Raimondo
S
S
Peiretti
P G
PG
Vercelli
A
A
Alloatti
G
G
Tomasinelli
C E
CE
Danni
O
O
Boccuzzi
G
G
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004032:Diet; D004041:Dietary Fats / Q000633:toxicity*; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D009206:Myocardium / Q000473:pathology; D009218:Myosins / Q000096:biosynthesis; D009336:Necrosis / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011817:Rabbits
D004041:Dietary Fats; D017127:Glycation End Products, Advanced; D003687:Dehydroepiandrosterone; D012313:RNA; D009218:Myosins