Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients

Abstract

Leptin, the 16 kDa product of the ob gene, is a an adipocyte-secreted hormone that centrally regulates weight. However, the physiological role of leptin is not limited to the regulation of food intake and energy expenditure, and leptin has a variety of effects in peripheral tissues, such as a regulatory role modulating the immune system. Thus, leptin receptor is expressed in human peripheral blood mononuclear cells, mediating the leptin stimulation of proliferation and activation, the production of proinflammatory cytokines from cultured monocytes, and the prevention of apoptotic death in serum-deprived monocytes. Because leptin can stimulate monocytes and the production of reactive oxygen species (ROS) are the result of monocyte activation, we investigated the effect of leptin on ROS production by human monocytes in vitro. Oxidative burst was measured by oxidation of the redox-sensitive dye 2',7'-dichlorofluorescein diacetate, and analysed by flow cytometry. We have found that stimulation with leptin produces oxygen radical formation by monocytes. This effect is dependent on the dose and maximal response is achieved at 10 nM leptin. Because HIV infection induces the production of ROS, we next investigated the effect of leptin on ROS production in monocytes from HIV-positive (HIV+) subjects. We have also found that monocytes from HIV+ subjects spontaneously produced increased amounts of free radicals. In contrast, leptin stimulation of monocytes from these patients partially inhibited the production of ROS. This effect of leptin was also dependent on the dose and maximal effect was achieved at 10 nM. The effect of leptin stimulating the production of ROS is consistent with the proinflammatory role in the immune system. On the other hand, the inhibitory effect on monocytes from HIV+ subjects may be explained by the attenuation of the oxidative burst by a delayed activation of monocytes in a hyperinflammatory state.