Figure 4.

After passing the barrier formed by enterocytes (step 1), LPS interacts with the LPS-binding protein, known as LBP (step 2). The complex then interacts with the CD14 placed on the membrane of the target cells (step 3). Then, CD14 transfers LPS into the receptor pocket of the complex constituted by TLR4 (Toll-like receptor 4) and MD2 (myeloid differentiation-2) triggering a cascade of intracytoplasmic events which culminates with the entry of NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) into the nucleus and subsequent transcription and translation into proteins (mainly cytokines) with specific inflammatory characteristics (step 4). The presence of these cytokines, feeds phenomena such as metabolic endotoxemia and tissue insulin-resistance (step 5). Both, by acting on the different organs, have different consequences. In the liver, they promote the development of NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), cirrhosis and cancer. In the striatal-skeletal musculature they promote accumulation of intramyocellular lipid and reduction of glycogen neo-synthesis. In the adipose tissue they promote inflammation. At cardiac and cardio-vascular levels they predispose individuals to an increased risk of myocardial infarction and thrombus growth. Finally, in the brain, they probably promote pathologies such as anxiety and depression.