Biochemistry, Department of


Date of this Version



Published in Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry, Volume 9, Issue 1, 2009, pp 1-2.

DOI : 10.2174/187152209788009779


Copyright © 2009 Bentham Science. Used by permission.


The composition of dietary fat influences tissue fatty acid composition, which in turn impacts cellular function through a number of different processes. This includes changes in signaling, lipid metabolism, and transcriptional activities that normally function to maintain intracellular fatty acid homeostasis. The consumption of high levels of dietary fat in excess of caloric expenditure is linked with obesity and the disruption of normal homeostatic mechanisms governing lipid metabolism. Data from the Centers for Disease Control and Prevention show that obesity (defined as a BMI≥30) represents a considerable health concern in the United States. Of particular note is that for adult men, the prevalence of obesity was 33% in 2006; the prevalence for adult women was slightly higher at 35%. Obesity is also of concern for children and adolescents where in 2006, 16% were considered obese (above the 95th percentile of the 2000 BMI-for-age growth charts).

Statistics released by the American Heart Association show that the rise in obesity correlates with high low-density lipoprotein-cholesterol (LDL-C) levels. In 2004, nearly 33% of adults in the United States (age 20 and older) had LDL-C levels of 130 mg/dL or higher. Obesity is associated with disturbances in lipid metabolism including triglycerides, free fatty acids and lipoprotein cholesterol. One common finding in obese individuals is elevated levels of circulating free fatty acids that in turn increases fatty acid internalization and ectopic accumulation of triglycerides. Such disturbances in normal lipid metabolic homeostasis are associated with changes in fatty acid oxidation, accumulation of reactive oxygen species, the synthesis of ceramide and ER stress. The correlation between chronically elevated plasma free fatty acids and triglycerides and low highdensity lipoprotein-cholesterol (HDL-C) levels with the development of obesity, insulin resistance and cardiovascular disease has led to the hypothesis that decreases in pancreatic insulin production, cardiac failure, arrhythmias, and hypertrophy are due to aberrant accumulation of lipids in these tissues. This Special Issue of Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry, with a focus on dietary lipid absorption, is particularly timely given the obesity epidemic and comes from many of the leading experts in fatty acid and sterol transport. These review articles cover five general areas: [1] Fatty acid transport, with a focus on fatty acid translocase (CD36) and members of the fatty acid transport protein (FATP) family; [2] sterol transport, with a focus on Niemann-Pick C1-Like 1 (NPC1L1) and ATP binding cassette transporters G5 and G8 (ABCG5/ABCG8); [3] intracellular fatty acid trafficking, with a specific focus on liver fatty acid binding protein (L-FABP); [4] therapeutic properties of n-3 polyunsaturated fatty acids; and [5] chylomicron synthesis with a focus on regulation and the role of apolipoproteins.