**3.2 Reverse cholesterol transport (RCT)**

Existing studies have investigated that extracellular levels, HDL molecular content and the activities of ABC transporter determine the cholesterol efflux. Also, previous reports have indicated that cellular cholesterol homeostasis, HDL-mediated efflux together with ABCG1 and cholesterol efflux by apoA-I/ ABCA1 plays a significant regulatory step in several cellular activities, such as proliferation, differentiation and mobilization of haemopoietic cells [26]. The RCT described a mechanism by which the body removes excess cholesterol from peripheral cells and tissues and delivers it to the liver after conversion to bile acids. The cholesterol will then be redistributed to other tissues or excreted from the body through the gallbladder, or to adrenals, testes, and ovaries for the synthesis of steroid hormones. Because cholesterol could not be metabolized by peripheral tissues, it must be transported back to the liver for removal through a pathway known as "reverse cholesterol transport" (**Figure 3**) determined by the HDL and its precursors [29]. The HDL-C is the main lipoprotein involved in this process, followed by the intestine, while the liver produces the protein Apo A-1 (70% of the protein content of HDL-c), which passes through the bloodstream and goes to peripheral tissues, such as the heart. In the circulation, Apo A-1 interacts with receptors in several cell types, including hepatocytes, enterocytes, and macrophages, known as ATP-Binding Cassette, Sub-Family A, Member 1 (ABCA1) [33]. In macrophages, the immune system specialized in phagocytosing particles, the interaction with this protein forces the cholesterols and some phospholipids to move toward the molecule Apo A-1. This interaction leads to the formation of nascent HDL-c particles (pre-b HDL), which can subsequently interact with scavenger receptor class B member 1 (SR-B1) and ATP-binding cassette, sub-family G, member 1 (ABCG1), and then incorporate more cholesterol to form a mature molecule of HDL-C (α-HDL), catalyzed *Non-Alcoholic Fatty Liver Disease: Pathogenesis and the Significance of High-Density… DOI: http://dx.doi.org/10.5772/intechopen.108199*

by the enzyme LCAT. Cholesterols are delivered to the liver in both direct and indirect ways. In a direct way, mature molecules of HDL-C interact with SR-B1 in the liver, which permits the transfer of its cholesterol content, and the resulting HDL-C molecule can enter circulation and initiate another RCT process. The mature molecules of HDL-C can indirectly transfer its cholesterol content to apolipoproteins B-100 (Apo B-100), particularly to the LDL, in exchange for triacylglycerol molecules, a process catalyzed by the enzyme CETP, and hence, these lipoproteins can be linked with their liver receptors and deliver their cholesterol content. The CETP was also identified to catalyze the reverse transference, i.e., triacylglycerol from HDL-C in exchange for Apo B-100 cholesterol. The reduction in the synthesis of hepatic cholesterol leads to increased hepatic LDL-receptors, which bind and reduces the synthesis of circulating LDL and its precursors; IDL and VLDL [34]. The HDL cholesterol content in plasma may therefore be a crucial modulator to treat and prevent NAFLD since this molecule exerts anti-inflammatory functions as well as positive effects on CRT. Furthermore, recent studies have suggested that the functionality of HDL-c shows a much greater potential in some conditions, including dyslipidaemia and NAFLD [32, 35].
