Expression of retinoic acid, triiodothyronine, and glucocorticoid hormone nuclear receptors is decreased in the liver of rats fed a hypercholesterolemia-inducing diet.

ABSTRACT

Several studies have shown that dietary factors modulate cell signaling pathways. The aim of this study was to determine whether a hypercholesterolemia-inducing diet rich in saturated fat and cholesterol modifies rat liver expression of the nuclear receptors of retinoic acid (RAR), triiodothyronine (TR), and glucocorticoid hormone (GR), which are transcriptional factors. The experimental diet contained coconut oil 25 g/100 g as a source of lipids, cholesterol 1 g/100 g, and cholic acid 0.5 g/100 g, and the control diet contained olive oil 5 g/100 g. After 26 days of feeding the hypercholesterolemia-inducing diet, a lower binding capacity of the nuclear receptors and a smaller amount of their mRNA were observed. Moreover, the activities of malic enzyme (ME) and tyrosine aminotransferase (TAT), whose gene promotors contain a response element to TR and GR, respectively, were significantly decreased. These changes occurred in a cellular environment characterized by a high level of cholesterol and free fatty acids (FFAs). Thus, two nonexclusive hypotheses can be proposed to explain this decreased expression of nuclear receptors, one emphasizing the effect of lipidic components on the cellular amount of receptor ligands (retinoic acid [RA] and triiodothyronine [T3]), the other emphasizing a modification of the balance between nuclear receptors that could impede the upregulation of TR and RAR.