Abstract
Hemin is an activator of heme oxygenase-1 (HO-1), an enzyme catalyzing heme degradation. Up-regulation of HO-1 is observed in response to various pathological conditions. Moreover, pharmacological activation of HO-1 is associated with numerous beneficial effects in the organism. Hemin was shown to exert, among other, anti-diabetic and anti-obesity properties. These effects are strongly linked with adipose tissue. However, the direct influence of hemin on metabolism of the fat cells have not been explored. The present study aimed to determine the short-term effects of hemin on metabolism of the primary rat adipocytes. We focused on processes directly related to lipid accumulation, such as lipogenesis and lipolysis. For this purpose, the isolated cells were subjected for 2 h to 40 µM hemin, and effects of this compound on insulin-stimulated glucose conversion to lipids, lactate release, lipolysis induced by various stimuli, and also on the antilipolytic action of insulin were determined. It was shown that hemin did not affect insulin-induced lipogenesis and lactate release. However, hemin significantly decreased lipolysis stimulated by epinephrine. The inhibitory effect of hemin on epinephrine-induced lipolysis was not abolished in the presence of SnMP, an inhibitor of HO-1, which suggests hemin action irrespective of this enzyme. Similar inhibitory effects on epinephrine-induced lipolysis were observed in the presence of 3 and 12 mM glucose. Moreover, hemin was shown to reduce epinephrine-induced lipolysis also when glucose was replaced by alanine or by succinate. Apart from changes in epinephrine action, it was found that the lipolytic response of the adipocytes to isoproterenol was also diminished by hemin. However, hemin failed to affect lipolysis stimulated by dibutyryl-cAMP (a direct activator of protein kinase A), forskolin (an activator of adenylate cyclase), and also by DPCPX (an adenosine A1 receptor antagonist). Additionally, epinephrine-induced lipolysis was shown to be decreased by insulin, and this effect was deepened in the presence of hemin. These results indicate that short-term exposure of the adipocytes to hemin does not affect processes related to glucose metabolism, such as lipogenesis and lactate release. However, hemin was found to decrease the lipolytic response to adrenergic stimulation, which is associated with reduced lipid release from adipocytes. Moreover, our results indicate that hemin is also capable of diminishing the exaggerated lipolysis, which occurs in the presence of supraphysiological concentrations of glucose.
Highlights
Hemin is a breakdown product of hemoglobin and is the oxidized form of heme
It was revealed that, to effects related to lipogenesis, lactate release was not significantly changed in the presence of hemin (Fig. 1B)
Results of the present study indicate that pathways of glucose metabolism related to lipogenesis and lactate formation are unchanged after short-term exposure of the primary rat adipocytes to hemin
Summary
Hemin is a breakdown product of hemoglobin and is the oxidized form of heme. Hemin is one of the pharmacological activators of heme oxygenase-1 (HO-1), an enzyme which is involved in heme degradation. Mammalian heme oxygenase has two isoforms, HO-1 and HO-2. HO-1 is activated in response to increased amounts of heme (Abraham & Kappas, 2008; Ndisang, 2010; Wegiel et al, 2014). Heme degradation, catalyzed by HO-1, is thought to be critical for cellular defense. This is associated with increased formation of heme-derived products, such as iron, CO and biliverdin. (Abraham & Kappas, 2008; Ndisang, 2010; Wegiel et al, 2014) This is associated with increased formation of heme-derived products, such as iron, CO and biliverdin. (Abraham & Kappas, 2008; Ndisang, 2010; Wegiel et al, 2014)
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