[THE BRAIN LEPTIN SIGNALING SYSTEM AND ITS FUNCTIONAL STATE IN METABOLIC SYNDROME AND TYPE 2 DIABETES MELLITIS].

The brain leptin signaling system has a key role in regulation of feeding behavior, peripheral metabo- lism, functions of the nervous and endocrine systems, and disturbances in this system lead to metabolic disorders, including metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). This system is activa- ted by leptin produced by adipocytes and then penetrates into brain through the blood-brain barrier, where leptin binds to leptin receptors OBRb. This leads to activation of tyrosine kinase JAK2, which phosphory- lates tyrosine-containing sites located in the cytoplasmic domain of the receptor, resulting in stimulation of activity of phosphatidylinositol-3-kinase, the transcription factors STAT3 and STAT5, phosphatase SHP2, and mitogen-activated protein kinase. Decrease in number of functionally active leptin receptors and disturbances in the downstream components of leptin cascades in neuronal cells lead to development of leptin resistance. Since the leptin system in hypothalamic neurons is closely linked to the insulin, mela- nocortin, dopaminergic and other signaling systems, leptin resistance induces a lot of functional disorders in the CNS and on the periphery. The restoration of the brain leptin system functions is one of the promi- sing approaches to treatment and prevention of metabolic disorders, including MS and DM2. The review analyzes data on structural and functional organization of the leptin signaling system, its functional, interaction with other brain signaling systems, the causes and effects of central leptin resistance, as well as the approaches to restore the functions of the hypothalamic leptin system in MS and DM2. Key words: leptin, leptin resistance, hypothalamus, JAK2-kinase, leptin receptor, diabetes mellitus, metabolic syndrome, melanocortin system, phosphatase inhibitor.