Obesity and Atherogenic Dyslipidemia Vaneeta Bamba, Daniel J. Rader  Gastroenterology  Volume 132, Issue 6, Pages 2181-2190 (May 2007) DOI: 10.1053/j.gastro.2007.03.056 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 In the fed state, dietary lipids are hydrolyzed by lipases to produce NEFAs, which are re-esterified by the enterocyte into TG and packaged with apoB-48 by MTP into chylomicrons and secreted. Chylomicrons bind to endothelial LPL in adipose tissue, and apo C-II activates LPL resulting in hydrolysis of TG and generation of NEFAs. NEFAs are re-esterified by the adipocyte into TG and stored until lipolysis is activated. Resulting chylomicron remnants are targeted for hepatic catabolism. Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 TRL TGs are hydrolyzed by LPL, and NEFAs are taken up by the adipocyte and stored as TG until there is a demand for FA release by peripheral tissues. Adipocyte TGs are hydrolyzed by HSL and ATGL. Stimulation of lipolysis occurs primarily via catecholamines such as adrenaline and noradrenaline and leads to activation of HSL. Insulin mediates antilipolytic action through the insulin receptor to promote storage of TAG within the adipocyte. Beta-hydroxybutyrate, via GPR109A, and alpha-adrenergic stimuli (not shown), are also inhibitors of lipolysis. Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 In the fasting state, lipolysis of TG in adipocytes releases NEFAs that are bound to albumin and circulate back to the liver where they have multiple possible fates. Some NEFAs are re-esterified by the hepatocyte into TG, and newly synthesized TG is either packaged with apoB-100 by MTP into VLDL and secreted, or stored in cytosolic lipid droplets. In the case of muscle energy demand, VLDL TGs are hydrolyzed by endothelial LPL in muscle, generating NEFAs that are used for energy. Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions

Figure 4 HDL metabolism is influenced by a variety of factors, including catabolism by the liver and kidneys, CETP-mediated lipid exchange with apoB containing lipoproteins, and lipolytic modification by hepatic lipase and endothelial lipase. Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions

Figure 5 Obesity and adipose tissue may influence HDL metabolism through a variety of potential mechanisms. Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions

Daniel J. Rader, MD Gastroenterology 2007 132, 2181-2190DOI: (10.1053/j.gastro.2007.03.056) Copyright © 2007 AGA Institute Terms and Conditions