DIET-INDUCED OBESE RATS ARE ASSOCIATED WITH LEPTIN RESISTANCE IN THE MEDIAL PREOPTIC AREA OF THE ANTERIOR HYPOTHALAMUS

Leptin is an adipokine that reduces food intake and increases energy expenditure via activation of the JAK2-STAT3 signalling pathway in mammal hypothalamic neurons. The degree of leptin-mediated STAT3 phosphorylation (pSTAT3) serves as a marker of cellular leptin responsiveness. Neurons, expressing the long form of the leptin receptor, have been found in several hypothalamic sites, including medial preoptic area (MPA). The failure of elevated leptin levels to suppress feeding and mediate weight loss in common forms of obesity defines a state of so-called leptin resistance. In this study, we demonstrate that feeding rats with cafeteria diet for a period of 9 weeks results in a significant increase in body weight, Lee index and serum leptin concentration. Using immunohistochemical method for determining pSTAT3, we observed impaired leptin signal transduction in the MPA of male Wistar rats with diet-induced obesity. These data suggest the development of leptin resistance at the level of STAT3 activation in MPA of obese rat. The results are consistent with our previous report of disturbances in leptin effects on the firing rate of MPA neurons in rats with experimental model of obesity.