Effects of the activation of heme oxygenase-1 on hormonal and metabolic changes in rats fed a high-fat diet.

Heme oxygenase-1 (HO-1) is the inducible isoform of the heme oxygenase system, which catalyzes heme degradation. Up-regulation of this enzyme under pathological conditions is associated with beneficial effects in the whole organism. However, the potential of HO-1 in the alleviation of disturbances induced by a high-fat diet (HFD) is poorly elucidated. The present study was undertaken to determine the effects of pharmacological activation of HO-1 by hemin on some hormones and metabolic parameters in rats fed an HFD for 8 weeks. It was demonstrated that, in rats fed an HFD, blood glucose levels were increased compared with control animals. However, this hyperglycemic effect was alleviated by induction of HO-1. The observed decrease in glycemia was not associated with an increase in blood insulin concentrations, but was accompanied by improved glucose tolerance, which points to the potentiation of insulin action. Concentrations of free fatty acids were elevated in response to HFD; however, this effect appeared to be mitigated by hemin. Rats fed an HFD displayed clear-cut hyperleptinemia, which is a hallmark of leptin resistance. This derangement was effectively prevented by hemin therapy. Feeding with an HFD also increased blood ghrelin levels, whereas hemin slightly reduced blood ghrelin concentration. Carbohydrate and lipid metabolism in the liver of rats on an HFD was found to be disturbed, leading to increased lipid accumulation and reduced glycogen stores. However, negative changes in liver metabolism were partially attenuated as a result of induction of HO-1. Our results show that activation of HO-1 by hemin ameliorates some changes induced by HFD feeding. Normalization of blood leptin levels in these animals seems to be the most relevant finding, since hyperleptinemia is associated with dysregulation of energy homeostasis and with numerous other disorders. These results indicate that the HO system holds great potential to alleviate alterations induced by HFD.