_______________________________________ Hyperlipidemias and Atherosclerotic Cardiovascular Disease
with a positive family history of hyperlipidemia or premature CVD in male relatives younger than 55 years of age or female relatives younger than 65 years; other risk factor indications for screening in childhood/adolescence include [241]: • Overweight/obesity (BMI >85th percentile) • Hypertension (blood pressure >95th percentile) • Diabetes • Medical conditions associated with lipoprotein abnormalities (e.g., organ transplant, nephrotic syndrome) • Family history of pancreatitis in multiple family members (suspected primary hypertriglyceridemia) The suggested laboratory screening evaluation should include complete lipid profile, basic metabolic profile, liver function tests, and assessment of thyroid function [241].
partially hydrogenated fats) have physical properties similar to saturated fats and are solid at room temperature. They are inexpensive to produce, give foods a desirable texture and taste, have a long shelf-life, and can be reused to deep-fry foods. These properties make trans fats particularly attractive to commercial enterprises and fast-food restaurants. However, their increased dietary intake is associated with increased ASCVD. Awareness of this link has led to the concerted effort to decrease or eliminate their availability and dietary intake. Clear information on trans fats, particularly useful for patients and the general population, is readily available from the American Heart Association ( Resources ). Triglycerides are a combination of three fatty acids attached to a single glycerol molecule. They are the main source of dietary fat and can also be synthesized in the liver from intermediary metabolites of excess carbohydrates. Triglycerides accumulate in adipose tissue and muscle cells and can later be mobilized as non-esterified free fatty acids as a source of energy when dietary sources are not readily available. Triglycerides and cholesterol are virtually insoluble in water; to facilitate their transport in plasma and lymph, they are packaged in larger spherical macromolecules known as lipoproteins. Like cholesterol, hypertriglyceridemia plays a significant role in the process of atherogenesis. ABSORPTION, SYNTHESIS, AND METABOLISM Circulating lipids have two distinct but interrelated origins and metabolic pathways: the exogenous (i.e., dietary source) and the endogenous pathways (i.e., hepatic synthesis) [52]. Exogenous Pathway Dietary lipids provide 30% to 40% of calories in Western diets. With the exception of the essential fatty acids (e.g., linoleic, linolenic), most lipids can also be synthesized by humans. Triglycerides, specifically, account for more than 95% of dietary lipid intake. Cholesterol from animal sources and small amounts of plant sterols comprise the majority of dietary lipid intake. Free fatty acids, phospholipids, and fat- soluble vitamins account for the remaining lipids from dietary sources [46; 50; 53]. Dietary fat is digested by enzymes produced in the mouth, stomach, and pancreas. The small intestine is the main site of lipid transformation and absorption. In the small intestine, triglycerides are hydrolyzed by gastric and pancreatic lipases, phospholipids are transformed by phospholipase A2 into lysophospholipids and fatty acids, and cholesterol is hydrolyzed by bile salts and pancreatic hydrolase (also known as cholesterol esterase). Studies have established that cholesterol absorption in the small intestine is regulated by selective transporters, such as the Niemann-Pick C1 like 1 (NPC1L1). Selective inhibition of NPC1L1 prevents intestinal absorption of dietary cholesterol, a mechanism targeted by ezetimibe, a lipid-lowering drug. In
AN OVERVIEW OF LIPIDS
PHYSIOLOGIC ROLES Lipids play a crucial role in living organisms as a source of energy and as structural constituents of cell membranes and complex molecules such as steroids and eicosanoids (e.g., prostaglandins, thromboxane A2, leukotrienes) and lipid- soluble vitamins [30; 50; 51]. In brief, the most important lipids are phospholipids, cholesterol, fatty acids, and triglycerides. Phospholipids are structural components of cell membranes, myelin, lipoproteins, and blood clotting factors. Cholesterol is a structural component of cell membranes and a precursor of other steroids, namely steroid hormones, bile acids, and signaling molecules. Cholesterol is mainly synthesized in the liver but is also absorbed in the intestine from dietary sources and enterohepatic circulation. Fatty acids are a source of energy. Their general structure is represented as R-COOH, where R represents a hydrocarbon chain. More than 100 fatty acids have been identified, and they differ on length of the hydrocarbon chain and number of carbon-carbon double bonds. Fatty acids without carbon- carbon double bonds are classified as saturated; those with carbon-carbon double bonds are classified unsaturated. Unsaturated fatty acids are further differentiated into monounsaturated or polyunsaturated based on the number of carbon-carbon double-bonds. Saturated fatty acids are waxy solids at room temperature, while unsaturated fatty acids are liquids. Intracellular free fatty acids are present in trace amounts and esterified with glycerol to form more complex lipids, including triglycerides. Most double bonds in unsaturated fatty acids are in the cis form. Some edible fats, including hydrogenated vegetable products such as oils, margarines, and shortenings, are rich in trans fatty acids. Trans fatty acids (also known as
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MDNE1526
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