Fatty Acids and Triglycerides

Experiments with monkeys given intramuscular injections of a mineral oil emulsion with [l-14C] -hexa-decane tracer provide data illustrating that absorbed C-16 hydrocarbon (a major component of liquid petrolatum) is slowly metabolized to various classes of lipids (Bollinger 1970). Two days after injection, substantial portions of the radioactivity recovered in liver (30%), fat (42%), kidney (74%), spleen (81%), and ovary (90%) were unmetabolized -hexadecane. The remainder of the radioactivity was found as phospholipids, free fatty acids, triglycerides, and sterol esters. Essentially no radioactivity was found in the water-soluble or residue fractions. One or three months after injection, radioactivity still was detected only in the fat-soluble fractions of the various organs, but 80-98% of the detected radioactivity was found in non-hydrocarbon lipids. 

In addition to the studies of clinical biological changes in lipid profile levels in patients with major depression, the mechanism of lipid metabolism should be noted and discussed [133], In past studies, the main plasma lipid transport forms have been free fatty acids, triglycerides, and cholesteryl esters. 

Anesthetized rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin. The use of anesthetized rats represents more a principal assessment of the pharmacological side effect potential since the candidate compound must be administered intravenously or intraperitoneally (enteral/intestinal administration should be avoided due to the anesthesia-induced decrease in intestinal motility with subsequent impairment of enteral absorption), compared to the study in conscious rats in which the candidate compound can be studied after oral administration, which in most cases represents the clinical route of administration for small molecular drugs. 

Conscious rats are used for testing the side effect potential of a candidate compound on intermediary metabolism in liver, muscle and adipose tissue with subsequent effects on metabolic blood parameters (e.g. glucose, lactate, free fatty acids, triglycerides) and insulin after oral administration, which represents in most cases the clinical route of administration for small molecular drugs. 

Rats weighing 180-240 g are kept on standard diet. Groups of 8 non-fasted animals are treated orally with various doses of the test compounds suspended in 0.4% starch suspension. One control group receives the vehicle only. Blood is withdrawn from the tip of the tail immediately before, and 1,2,3,5, and 24 hours after administration of the candidate compound. Blood glucose is determined in 10 pi blood samples collected from the tip of the tail. If pharmacokinetic data for the candidate compound are already available, when performing this test, additional blood samples (100 pi) should be taken at max by retro orbital bleeding for detection of free fatty acids, triglycerides and insulin. 

Figure 1.10 Examples of a fatty acid, triglyceride and steroid. From Voet, Voet Pratt Fundamentals of Biochemistry, 2nd edn 2006 Voet, Voet Pratt reprinted with permission of John Wiley Sons, Inc.

Aliphatic EC>16-EC35 Fraction. Aliphatic hydrocarbons in this fraction are not expected to undergo extensive metabolism in animals or humans. In monkeys, 2 days after intramuscular injection of a mineral oil emulsion with a radiolabeled C16 hydrocarbon Oz-hexanedecane), substantial portions (30-90%) of radioactivity in various tissues existed as unmetabolized n-hexanedecane. The remainder of the radioactivity was found as phospholipids, free fatty acids, triglycerides, and sterol esters. No radioactivity was found in water-soluble fractions (ATSDR 1997b). The common presence of lipogranulomata in human autopsies and the widespread dietary exposure to mineral oils and waxes (Wanless and Geddie 1985) are consistent with the concept that aliphatic hydrocarbons in this fraction are slowly metabolized. 

H.C. Chen and R.V. Farese, Fatty acids, triglycerides, and glucose metabolism recent insights from knockout mice, Curr. Opin. Clin. Nutr. Metab. Care, 2002, 5, 359-363. 

Previous studies have shown that fatty acids are quite soluble in supercritical carbon dioxide. Solubility levels of 1 to 10% are easily obtained for fatty acids, triglycerides, and esters in CO2. In addition, several previous patents exist for the extraction of fatty materials using supercritical fluids. Therefore, a process which uses supercritical CO2 for the extraction of fatty acids from spent nickel catalyst should be successful. 

Oil red O is used to stain lipids, fatty acids, triglycerides, and cholesterol to make them visible under light microscopy. Like other lysochromes (fat stains), oil red O is more soluble in lipids than in its alcohol solvent which causes it to preferentially stay in lipid droplets (Kiernan, 1981). This stain is often used to demonstrate adipogenic differentiation of stem or progenitor cells. 

---