Lipid modulation and systemic inflammation.

Lipids are important sources of energy (9 kcal/g) for the cell. They are also important biochemical, structural, and regulatory compounds in the human body and are required for optimal tissue function, growth, and repair. It is now clear that the source of lipid in the diet can modulate the inflammatory response to stress and disease. Lipids are classified according to their chain length, position and number of double bonds. Short-chain fatty acids have 2 to 4 carbons (e.g., acetate, propionate, butyrate) and are primary fuels for intestinal cells (especially the colon). They are produced by gut bacterial fermentation of dietary fiber. Medium-chain fatty acids have 6 to 12 carbon atoms. They are water soluble and directly absorbed from the gut into the blood. Medium-chain fatty acids are degraded by beta-oxidation and enter the mitochondria independent of transporters. Long-chain fatty acids have 14 to 24 carbon atoms. Long-chain fatty acids represent the primary lipids that comprise cellular membranes and are precursors for a variety of regulatory lipid molecules (e.g., prostaglandins, leukotrienes, thromboxanes). Long-chain fatty acids are absorbed from the gut into the lymphatics and require carnitine for transport into the mitochondrium for oxidation. Fatty acids with double bonds are called unsaturated fatty acids. Those with two or more double bonds are polyunsaturated. One system for naming fatty acids is by numeric nomenclature in which the number of carbon atoms is separated from the number of double bonds by a colon. Thus, linoleic acid is designated 18:2 (18 carbon atoms, two double bonds). Fatty acids also are classified according to the position of the first double bond from the methyl end (n terminal) of the molecule. Thus, n-3 fatty acids have their first double bond three carbons in from the methyl terminal (Table 1). The remainder of this article deals with long-chain fatty acids. Membranes vary in their lipid content from approximately 50% to 75%. Most cell membranes contain approximately 50% lipid and 50% protein. The type of fatty acid incorporated into cell membranes depends on the type of lipid present in the diet. Changes in the relative amounts and types of long-chain fatty acids in the diet alter membrane composition, fluidity, receptor action, membrane bound enzyme activity, ion channel function, hormone binding, signal transduction, eicosanoid production, and cell function. Essential fatty acids are lipids required for normal cell function that cannot be synthesized in the body. Mammalian cells are able to synthesize saturated and n-9 and n-7 series unsaturated fatty acids from acetyl coenzyme A (CoA) but lack the delta-12 and delta-15 desaturase enzymes for insertion of a double bond in the n-3 or n-6 position of fatty acids. Thus, the body must obtain n-3 and n-6 lipids from the environment (diet). The essential fatty acids for animals are the polyunsaturated fatty acids (PUFAs) linoleic acid (18:2, n-6) and alpha-linolenic acid (18:3, n-3). These essential fatty acids are substrates for many of the major regulatory lipids in the body. Longer chain and more unsaturated n-6 and n-3 fatty acids such as arachidonic acid (20:4, n-6), eicosapentaenoic acid (EPA, 20:5, n-3), and docosahexaenoic acid (DHA, 22:6, n-3) can be synthesized from these essential fatty acids by desaturation and elongation. Desaturase activity is increased by insulin and inhibited by glucose, epinephrine, and glucagon. The body can synthesize nonessential fatty acids (n-7 and n-9) from glucose (i.e., acetyl CoA). The precursor of the n-6 long chain fatty acids is linoleic acid. It can be desaturated to gamma-linolenic acid (18:3, n-6). The precursor for the n-3 long-chain fatty acids is alpha-linolenic acid. It can be desaturated to stearidonic acid (18:4, n-3). Gamma-linolenic acid (18:3, n-6) can then be elongated to dihomo gamma-linolenic acid (20:3, n-6) and desaturated to arachidonic acid (20:4, n-6). Stearidonic acid (18:4, n-3) can be elongated (20:4, n-3) and then desaturated to produce EPA (20:5, n-3). EPA can be elongated and desaturated to DHA (22:6, n-3). EPA and DHA are found in high quantities in many marine (fish) oils. Deficiency of the essential fatty acids causes a deficiency syndrome characterized by immune dysfunction, infections, scaly dermatitis, hair loss, thrombocytopenia, and poor wound healing.