Fig. 10

Expression TLR4 in integrated tissues and organ systems of the body that regulate the insulin sensitivity. Toll-like receptor 4 (TLR4) present in adipocytes, initiates the inflammatory responses that release various pro-inflammatory mediators. Once, produced, these mediators are entred into the blood stream and thereby promote IR. Liver-resident macrophages known as Kupffer cells are made up of 10% of the cells in liver and 80%–90% of all tissue macrophages within the body. TLR4, expressed on Kupffer cells and other liver cell components, regulates the various inflammatory responses in liver. TLR4, expressed in skeletal muscles, has been shown to regulate the substrate metabolism in muscle, favoring glucose oxidation in the absence of insulin. Hypothalamus and mesolimbic area are important sites that modulate the energy expenditure, pancreatic β-cell function and IR in peripheral tissue. Expression of TLR4 in hypothalamus potentiates various inflammatory responses that contribute to the pathogenesis of IR. Adopted from Kim and Sears 2010