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Fatty acids are typically unbranched, long chain organic acids with different chain length. They are found in all living organism fulfilling three fundamental roles. Besides their function as part of molecules like phospholipids and glycolipids important for the cell-structure, they are often precursors of signalling molecules such as prostanoids in animals or phytohormones in plants. The third and best understood role of fatty acid is their role as an energy source, particularly in higher animals and plants. Thus, the absorption, distribution, metabolism and elimination of fatty acids have been well investigated for years (Lehninger 1970, Nelson and Cox, 2008).


Due to the role as nutritional energy source, fatty acids are absorbed from the lumen of the intestine by different uptake mechanisms depending on the chain length. Short- and medium chain fatty acids (C1 - C12) are rapidly absorbedviaintestine capillaries into the blood stream. For butyrate (C4) for example, an absorption rate of 1.9 µmol/cm2/h (= 167 µg/cm2/h) was found in the human intestine (McNeil et al., 1978). In contrast, long chain fatty acids (>C12) are absorbed into the walls of the intestinevilliand assembled intotriglycerides, which then are transported in the blood streamvialipoprotein particles (chylomicrons). This difference in the uptake mechanism of fatty acids is reflected by the percentage of absorption found when human infants were fed a diet containing different fat sources (Jensen et al., 1986). While an absorption of 99.9 % was found for C8 fatty acid, the long chain C18 fatty acid showed only 64.4 % absorption.

The dermal penetration of fatty acid is very variable based on the heterogeneous physico-chemical properties such as melting temperature, solubility and polarity. The polarity, for example, decreases with increasing chain lengths and/or the abolition of ionisable charged groups, so that they are less-water soluble but more permeable through lipophilic membranes like the skin. As an example, unsaturated long chain fatty acids like oleic acid (C18) have been shown to increase the transepithelial water loss significantly compared to shorter unsaturated fatty acids (Tanojo et al., 1998). Unsaturated long chain fatty acids are therefore used in pharmaceutical transdermal drugs as a flux enhancer for drugs that do not readily cross the skin-barrier on their own. However, the fatty acid itself remains within the lipophilic dermal layer due its polarity.

In contrast to the rapid uptake of fatty acidsviathe oral exposure route, fatty acids are in general poorly absorbed through skin, with a measured rate of less than 1 % after 24-hours exposure (Schaefer and Redelmeier, 1996). The dermal absorption of fatty acids ranged from moderate to very low according to QSAR calculations which are based on molecular weight, logPowand water solubility. The resulting calculated absorption rates are 0.021 mg/cm2for C8 octanoic acid, 0.005 mg/cm2for lauric acid (C12), and 0.26 µg/cm2for stearic acid (C18), respectively (Danish EPA Database, 2004). Thus, the dermal absorption is definitely lower than the absorption after oral uptake.

This was demonstrated in a study where excretion of azelaic acid was analyzed in urine after dermal application of six healthy male volunteers with a single treatment with 5 g of an anti-acne cream containing 20% azelaic acid and after oral application (Taeuber et al., 1992). While 61% of orally administered azelaic acid was detected in the urine, only 2.2% azelaic acid was found in the urine after dermal application.

The dermal uptake of fatty acid is further influenced by the fact that significant skin irritation/corrosion is observed for fatty acids with a chain length less than C10. In these cases local irritation/corrosion is considered as the primary effect.

Taken together the experimental and calculated data show that fatty acids are almost completely absorbed after oral intake, whereas only limited dermal uptake has to be expected.


Distribution and Metabolism

Fatty acids are absorbed through the intestine and transported throughout the body. Short chain fatty acids are taken up and transported complexed to albuminviathe portal vain into the blood vessels supplying the liver. Medium and long chain fatty acids are esterified with glycerol to triacylglycerides (TAGs) and packaged in chylomicrons (Spector, 1984). These are transportedviathe lymphatic system and the blood stream tohepatocytesin the liver as well as toadipocytesandmuscle fibers, where they are either stored (i.e. adipose tissue storage depots) or oxidized to yield energy. In addition, some cell types are known to synthesize medium and long chain fatty acidsviaelongation of shorter fatty acids (Hellerstein, 1999).

The quantitatively most significant oxidation pathway (β-oxidation pathway) is predominantly located in the cardiac and skeletal muscle. In a first step, the fatty acids are converted toacyl-CoAderivatives (aliphaticacyl-CoA) and transported into cells and mitochondria by specific transport systems. Then, theacyl-CoAderivatives are completely metabolized to acetyl-CoAor other key metabolites by the efficient enzymatic removal of the 2-carbon units from the aliphaticacyl-CoAmolecule (Coppack et al., 1994). The complete oxidation of fatty acidsviathe citric acid cycle leads to H2O and CO2(Coppack, 1994; MacFarlane, 2008). Other pathways for fatty acid catabolism also exist and include α- and ω-oxidation. The resulting main metabolites are acyl-carnitine, acetyl CoA, fatty acyl-CoA, propionyl-CoA and succinyl-CoA (Wanders et al., 2010).



Fatty acids are metabolised by various routes in the body to provide energy. Besides this, fatty acids are stored as lipids in adipose tissue, used as part of cellular membranes, as well as  precursors for signalling molecules and even long chain fatty acids. Thus, fatty acids are not expected to be excreted to any significant amount in the urine or faeces.



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Wanders, R.J. et al., 2010.Peroxisoms, lipid metaboism and lipotoxicity. Biochim Biophys Acta. 2010 Mar;1801(3):272-80.