GLOSSARY Saturated Fatty Acids (SFA) contain only single carbon-to-carbon bond. Most of the SFA occurring in nature have unbranched structures and an even number of carbon atoms. The melting point of SFA increases with chain length. Unsaturated Fatty Acids (UFA) contain one or more double bonds (carbon-tocarbon). Due to the presence of double bonds, unsaturated fatty acids are chemically more reactive than SFA.The unsaturated fatty acids can either occur in a cis or trans configuration. Monounsaturated Fatty Acids (MUFA) have one double bond in the fatty acid chain. In general, they have an even number of carbon atoms, between C14 to C24. Oleic acid (cis-9-octadecenoic acid or 9c 18:1) is the most frequently occurring cis -MUFA and is also the most widely distributed of all the natural fatty acids. Polyunsaturated Fatty Acids (PUFA) have more than one double bond in the fatty acid chain. The most important families, in terms of extent of occurrence and human health and nutrition, are the n-6 and n-3 families. Cis Fatty Acids are unsaturated fatty acids that contain adjacent hydrogen atoms on the doubly bonded carbon atoms i.e. the hydrogen atoms are on the same side of the double bond. Trans Fatty Acids (TFA) are unsaturated fatty acids that contain at least one non-conjugated double bond in the trans configuration, i.e. the hydrogen on the doubly bonded carbon atoms is in the trans configuration, resulting in a straighter shape.they have higher melting point than the cis isomers.there has been concern regarding their adverse nutritional effects. - Natural/ Ruminant Trans Fatty Acids: Some TFA are found naturally in small amount in ruminant animals and their products like various meat and dairy products. - Industrially Produced Trans Fatty Acids (I-TFA) result from the industrial processes such as hydrogenation/ refining of vegetable oils, frying of foods and food irradiation. Hydrogenation is a chemical reaction between molecular hydrogen (H 2 ) and another compound or element, usually in the presence of a catalyst. The process is commonly employed to saturate organic compounds. Hydrogenation typically constitutes the addition of pairs of hydrogen atoms to a molecule, generally an alkene. Partial hydrogenation is an important process for raising the melting points of liquid oils. At the same time, oxidative stability is enhanced by the reduction in the level of polyene acids but the nutritional value is reduced through reduction in essential fatty acids and increase in saturated and transfatty acids. Essential Fatty Acids (EFA)are long-chain unsaturated fatty acids derived from α-linolenic (Omega-3) acid and linoleic (Omega-6) acid. They cannot be synthesized by the human body and therefore they must be supplied through diet. xxiv
Omega-3 Fatty Acids (ώ 3) are unsaturated fatty acids having a common a carbon-carbon double bond in the n-3 position/ bond, counting from the methyl end. These have many health benefits and are considered essential i.e. are vital for normal metabolism. These include ALA, DHA, EPA. - Alpha-linolenic Acid (ALA) is an omega-3 fatty acid with 18 carbon chain (C18:3n-3). - Ecosapentanoic Acid (EPA) is a long-chain omega-3 fatty acid with 20 carbon chain (C20:5n-3). - Docosahexanoic Acid (DHA) is a long-chain omega-3 fatty acid with 22 carbon chain (C22:3n-3). Omega-6 Fatty Acids (ώ 6) are a family of unsaturated fatty acids that have in common a carbon-carbon double bond in the n-6 position/ bond, counting from the methyl end. These are essential fatty acid and include LA and AA. - Linoleic acid (LA) is an unsaturated omega-6 fatty acid with 18 carbon chain (18:2n-6). - Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid with 20 carbon chain, (20:4n-6). Eicosanoids are signaling molecules made by oxidation of twenty-carbon EFA. They exert complex control over many bodily systems, mainly in inflammation/ immunity and as messengers in the central nervous system. Eicosanoids are derived either from ω-3 or ω-6 EFA. The ω-6 eicosanoids are generally proinflammatory; ω-3s are much less. The amounts and balance of these fats in a person's diet will affect the body's eicosanoid-controlled functions, with effects on cardiovascular disease, triglycerides, blood pressure, and arthritis. There are four families of eicosanoids: the prostaglandins, prostacyclins, the thromboxanes and the leukotrienes. - Prostaglandin(PG) forms the prostanoid class of fatty acid derivatives (a subclass of eicosanoids). They have strong physiological effects such as regulating the contraction and relaxation of smooth muscle tissue. Prostaglandins are not endocrine hormones, but are locally acting messenger molecules. They differ from hormones, as they are not produced at a discrete site but in many places throughout the human body. - Thromboxane (TX) is a member of the eicosanoids family. It plays a major role in clot formation (thrombosis). Thromboxane is a vasoconstrictor and a potent hypertensive agent and it facilitates platelet aggregation. The two major thromboxanes are thromboxane A2 and thromboxane B2. Thromboxane-A synthase, an enzyme found in platelets, converts the arachidonic acid derivative prostaglandin H2 to thromboxane. Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets as well as increasing platelet aggregation. - Prostacyclin (PGI2) is also the member of the eicosanoids family. It chiefly prevents formation of the platelet plug involved in primary homeostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane xxv
(TXA2), strongly suggest a mechanism of cardiovascular homeostasis between the two eicosanoids in relation to vascular damage. Fatty acidsynthetase are a group of enzymes which are involved in the de novo formation of fatty acids in animals and plants but also chain lengthening of, for example, fatty acids from the diet (elongases). - Elongase are the enzymes that catalyze the elongation of an aliphatic chain, but especially one that elongates a fatty acid i.e. an enzyme that adds two carbons to the carboxyl-terminus of fatty acids. - Fatty acid desaturaseare enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/ carbon double bond. In the biosynthesis of EFA, an elongase alternates with different desaturases (for example, Δ6desaturase) repeatedly inserting an ethyl group and then forming a double bond. Lipoproteins are fat-carrying particles in the blood, each containing lipid (cholesterol, phospholipid, triglyceride) and protein. The function of lipoprotein particles is to transport lipids around the body in the blood. They include chylomicrons, very low density lipoprotein cholesterol (VLDL-c), intermediate density lipoproteins cholesterol (IDL-c), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c). The density of lipoproteins increases in proportion to their ratio of proteins to lipids. In general as the density of a lipoprotein increases, the size of the particles decreases. Very Low Density Lipoprotein Cholesterol (VLDL-c) is a type of lipoprotein made by the liver. VLDL-c is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. They are approximately 25-90 nanometers in size and have a density of ~0.98. VLDL-c contains approximately 5-12% protein, 50-55% triglycerides, 18-20% phospholipids, 12-15% cholesteryl esters and 8-10% cholesterol. VLDL-c is converted in the bloodstream to LDL-c and also acquires several apolipoproteins from plasma HDL-c and is a source of triglycerides for the cells. Intermediate Density Lipoproteins Cholesterol (IDL-c)are smaller than VLDLc, approximately 40 nanometers and have a density of ~1.0. IDL-c are composed of 10-12% protein, 24-30% triglycerides, 25-27% phospholipids, 32-35% cholesteryl esters and 8-10% cholesterol. IDL-c are derived from VLDL-c by triglyceride depletion and therefore, contain the same apolipoprotein as VLDL-c. IDL-c becomes LDL-c as its triglycerides are transferred to the cells. Low Density Lipoproteins Cholesterol (LDL-c)are also known as Bad Cholesterol. They are smaller than IDL-c, approximately 26 nanometers, and have a density of ~1.04. LDL-c contains 20-22% protein, 10-15% triglycerides, 20-28% phospholipids, 37-48% cholesteryl esters and 8-10% cholesterol. One of the protein components of LDL-c is apolipoprotein B100 which serves to bind the lipoprotein particles to LDL-c specific receptors on the surface of many cells. LDL-c is the main transporter of cholesterol and cholesteryl esters and makes up more than half of the total lipoprotein in plasma. High Density Lipoproteins Cholesterol (HDL-c) also known as good cholesterol are the smallest of the lipoproteins. HDL-c particles have a size of 6-12.5 nanometers and density of ~1.12. They contain approximately 55% protein, 3-15% triglycerides, 26-46% phospholipids, 15-30% cholesteryl esters and 2-10% xxvi
cholesterol and several types of apolipoproteins including apo-ai, apo-ci, apo- CII, apo-d and apo-e. HDL-c can bind to cholesterol in cell membranes by using the apo-ai protein to mediate the formation of cholesteryl esters. The apo-d protein in HDL-c then activates the transfer of cholesteryl esters to VLDL-c and LDL-c. HDL-c also transfers the apo-cii and apo-e proteins to chylomicrons and other low density lipoproteins. In the liver, the apo-e protein is used to recognize and absorb the remnants of lipoproteins so that excess cholesterol can be removed and converted to bile acids that are excreted into the duodenum (small intestine) through the bile duct. Lipoprotein a [Lp(a)] is type of cholesterol made by the liver that consists of a molecule apolipoprotein a, attached to LDL-c(bad cholesterol). High levels of Lp(a) increases the risk of atherosclerosis formation and coronary heart disease. Macrophages are cells produced by the differentiation of monocytes in tissues. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens. They are specialized phagocytic cells that attack foreign substances, infectious microbes and cancer cells through destruction and ingestion. Macrophages can be identified by specific expression of a number of proteins including CD14, CD11b, F4/80. Cytokines are substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication and serve as molecular messengers between cells. They are proteins, peptides or glycoproteins. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin. With regard to arthritis, cytokines regulate various inflammatory responses. Tumor necrosis factor-alpha (TNF-α) is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. It is produced chiefly by activated macrophages. The primary role of TNF- α is in the regulation of immune cells. TNF- α is able to induce fever, apoptotic cell death, sepsis (through IL1 & IL6 production), inflammation, inhibit tumorigenesis and viral replication. Dysregulation of TNF-α production has been implicated in a variety of human diseases, including Alzheimer's disease, cancer, major depression and inflammatory bowel disease (IBD). Interleukin-6 (IL-6) is a protein that in humans is encoded by the IL6 gene. IL-6 is an interleukin that acts as both, a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other tissue damage leading to inflammation. It supports the growth of ß cells and is antagonistic to regulatory T cells. IL-6 is relevant in many diseases such as diabetes, atherosclerosis, depression, Alzheimer's disease, prostate cancer and rheumatoid arthritis. Hence, there is an interest in developing anti-il-6 agents as therapy against many of these diseases. xxvii
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT), which are also known as white fat and brown fat, respectively, and comprise two types of fat cells. High Sensitivity C-reactive protein (hs-crp) is a protein produced by the liver and is a "marker" for inflammation, i.e. its presence indicates a heightened state of inflammation in the body. Inflammation is a normal response to many physical states including fever, injury and infection. Inflammation plays a role in the initiation and progression of cardiovascular disease. hs-crp measures an inflammatory response in the body and has been shown to play a role in atherosclerosis and blood clot formation. Cardiovascular diseases (CVD) is a general term used to describe disorders that can affect the heart (cardio) and/ or the body s vascular system particularly blood vessels. Most CVD reflect chronic conditions that develop or persist over a long period of time. However, some of the outcomes of cardiovascular diseases may be acute events such as heart attacks and stroke that may occur suddenly when vessel supplying blood to heart/ brain gets blocked. Popular usage of the term CVD is in reference to diseases that are associated with atherosclerosis.the causes of cardiovascular disease are diverse but atherosclerosis and/or hypertension are the most common. Atherosclerosis is a condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol found in food. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by LDL-c without adequate removal of fats and cholesterol from the macrophages by functional HDL-c. Dyslipidemia is defined as an elevation of the plasma cholesterol, triglycerides (TG) and/ or LDL-c or a decrease in the HDL-c level that may contribute to the development of atherosclerosis. Its cause may be primary (genetic) or secondary which can be detected by assessing the levels of total cholesterol (TC), TG, LDLc and HDL-c in plasma. Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions. Insulin Resistance (IR) refers to reduced glucose-lowering effects of insulin. It is a state in which a given concentration of insulin produces a less-than-expected biological effect. As a result there is in blood glucose levels outside the normal range along with other adverse health effects. The Metabolic Syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. It consists of an atherogenic dyslipidemia [i.e., elevated triglycerides and and low HDL-c], abdominal obesity and elevation of blood pressure as well as blood glucose. Endothelial Dysfunction refers to a systemic pathological state of the endothelium (the inner lining of blood vessels) and can be broadly defined as an imbalance between vasodilating and vasoconstricting substances produced by (or xxviii
acting on) the endothelium. Endothelial dysfunction is commonly associated with decreased nitric oxide (NO) bioavailability, which is due to impaired NO production by the endothelium and/ or increased inactivation of NO by reactive oxygen species. Endothelial dysfunction is thought to be a key event in the development of atherosclerosis. Fatty Acid Methyl Esters (FAMEs) are a type of fatty acid esters that can be produced by an alkali-catalyzed reaction between fats or fatty acids and methanol. These derivatives are mostly used for gas chromatography. Gas Chromatography (GC) is common type of chromatography with gas (hydrogen/ helium/ nitrogen)as the carrier/ mobile phase. The stationary phase is a microscopic layer of liquid or polymer on an inert solid support, inside a piece of metal tubing (column). Typical uses of GC include testing the purity of a particular substance/ separating the different components of a mixture.the mixture to be separated is carried by the mobile phase through thestationary phase. Because of different affinities (adsorption, partition) for thestationary phase the components of the mixture are delayed to differentdegrees as compared to the velocity of the mobile phase.it is useful for any volatile lipid compound, such as fatty acid methyl esters. Flame Ionisation Detector (FID) is the most universal detector for gas chromatography commonly used for the analysis of lipids such as fatty acid methyl esters, sterols and triacylglycerols. The detector measures ions that are generated when organic compounds are combusted. It can be used for virtually all organic compounds and has high sensitivity and stability. Scheffe's Test is a statistical test that is used to make unplanned comparisons, rather than pre-planned comparisons, among group means in an analysis of variance (ANOVA) experiment. It is a single-step multiple comparison procedure which applies to the set of estimates of all possible contrasts among the factor level means. xxix