Ceramide-1-linoleate

The exact mechanism of action of moisturizers and emollients is still unknown. Theoretically, the improvement in the barrier function could be due to absorption of the moisturizer into the delipidized stratum corneum, acting as an effective barrier, as suggested in a study on the effect of petrolatum (Ghadially et al. 1992). Due to a better knowledge of the structural organization of the horny layer with corneocytes embedded in between lipid bilayers (ceramides, cholesterol and free fatty acids in approximately equal quantities), new emollients could be developed to supply the missing elements in the bilayer structure after acute or chronic irritant contact. However, applications of ceramides, linoleic acid and a variety of other fatty acids alone have been reported to actually delay barrier recovery in acetone-treated murine skin, despite the fact that these lipids are required for barrier homeostasis. The only treatments that allowed normal barrier recovery were applications of complete mixtures of ceramide, fatty acid and cholesterol, or pure cholesterol (Man et al. 

Ceramides are classfied into five species (ceramide 1,2,3,4/5, and 6) according to their polarity. Yamamoto et al.6 and Imokawa et al.7 have reported that AD shows a significant decrease in the proportion of ceramide 1, which is a carrier of linoleate and responsible for water-barrier function. 

Hansen, H.S. and Jensen, B., Essential function of linoleic acid esterified in acylglucosyl ceramide and acylceramide in maintaining the epidermal water permeability barrier evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linoleate, Biochim. Biophys. Acta, 834, 357, 1985. 

Abraham, W., Wertz, P.W., and Downing, D.T., Linoleate-rich acylglucosyl ceramides of pig epidermis structure determination by proton magnetic resonance, J. Lipid Res., 26, 761, 1985. 

A mixed monolayer consisting of stearic acid (9.9%), palmitic acid (36.8%), myristic acid (3.8%), oleic acid (33.1%), linoleic acid (12.5%), and palmitoleic acid (3.6%) produces an expanded area/pressure isotherm on which Azone has no apparent effect in terms of either expansion or compressibility (Schuckler and Lee, 1991). Squeeze-out of Azone from such films was not reported, but the surface pressures measured were not high enough for this to occur. The addition of cholesterol (to produce a 50 50 mixture) to this type of fatty acid monolayer results in a reduction of compressibility. However, the addition of ceramide has a much smaller condensing effect on the combined fatty acids (ratio 55 45), and the combination of all three components (free fatty acids/cholesterol/ceramide, 31 31 38) produces a liquid condensed film of moderate compressibility. The condensed nature of this film therefore results primarily from the presence of the membrane-stiffening cholesterol. In the presence of only small quantities of Azone (X = 0.025), the mixed film becomes liquid expanded in nature, and there is also evidence of Azone squeeze-out at approximately 32 mN m. ... 

Walnuts contain about 65% lipids, however, considerable differences exist among varieties (range 52-70%, w/w) (1,40). Walnuts also contain 15.8% protein, 13.7% carbohydrate, 4.1% water, and 1.8% ash (w/w) (1). The fatty acid composition of walnut oil is unique compared with other tree nut oils for two reasons walnut oil contains predominantly linoleic acid (49-63%) and a considerable amount of ot-linolenic acid (8-15.5%). Other fatty acids present include oleic acid (13.8-26.1%), palmitic acid (6.7-8.7%), and stearic acid (1.4—2.5%) (Table 5) (40). The tocopherol content of walnut oil varies among different cultivars and extraction procedures and ranges between 268 mg/kg and 436 mg/kg. The predominant tocol isomer is y-tocopherol (>90%), followed by a-tocopherol (6%), and then (3- and 8-tocopherols (41). Nonpolar lipids have been shown to constitute 96.9% of total lipids in walnut oil, whereas polar lipids account for 3.1%. The polar lipid fraction consisted of 73.4% sphingolipids (ceramides and galactosylcera-mides) and 26.6% phospholipids (predominantly phosphatidylethanolamine) (42). Walnut oil contains approximately 1.8g/kg phytosterols (1), primarily p-sitosterol (85%), followed by A-5-avenasterol (7.3%), campesterol (4.6%), and, finally, cholesterol (1.1%) (42). 

However, TAGs and fatty acid are found abundantly in the human skin along with other components such as cholesterol and ceramides, more specifically in the human stratum corneum (outer layer of the skin) (58), which has been used to explain the high emolliency of some oils. Following this same rational, blends of other oils rich in oleic, linoleic, and palmitic acids such as olive, com, and palm oils are also widely used in cosmetics. 

Some substances, usually included in moisturizers, have other potential beneficial effects on dry skin (1) the L-isomer of lactic acid increases the endogenous synthesis of ceramides and promotes the incorporation of linoleate, instead of oleate, into ceramide 1 (Rawlings et al. 1996) (2) glycerol and other polyols prevent lipid crystallinity (Rawlings et al. 1994), increase SC humidity and promote corneosome digestion and, consequently, the unicellular invisible desquamation (Rawlings et al. 1995) (3) alpha-hydroxy acids improve keratinization and SC hydration (Leyden et al. 1995) and (4) silicones or silicone-based barrier creams may have an extra protective effect on external aggressions. 

The dermatitis associated with total EFA deficiency is most likely due to the role of linoleic acid in skin. Linoleic acid is the major fatty acid component of skin ceramides. This sphingolipid functions to prevent water loss through the skin (Simopoulos, 1989). Other fatty acids are not incorporated into skin ceramides to any great extent (Hansen and Jensen, 1985). Linoleic acid is also an efficient source of energy when compared to stearic and oleic acids. This is due to the more rapid oxidation of linoleic acid versus these 18 carbon saturated and mono-unsaturated fatty acids (Dupont, 1988). 

Studies in the mid 20th century identified the effects, in rats, of essential fatty acid deficiency (Table 5). Biochemically, the disease is characterized by changes in the fatty acid compositions of many ceU membranes whose functions are impaired (see British Nutrition Foundation, 1992 Gurr et al., 2002 for further details). One of the striking features of essential fatty acid deficiency in rats is skin dermatitis and water loss (see Mead, 1984). Epidermal lipids are rich in ceramides. The fatty acyl substituent in these is linoleic acid linked via its carboxylic acid group to the terminal methyl carbon of another fatty acid (34 1 n-9) to generate an extremely long-chain (52 carbons) stmcture. 

Thrush, A.B., Chabowski, A., Heigenhauser, G.J., McBride, B.W., Or-Rashid, M., and Dyck, D.J. 2007. Conjugated linoleic acid increases skeletal muscle ceramide content and decreases insulin senmsitivity in overweight, non-diabetic humans. Applied Physiology of Nutrition and Metabolism 32, 372-382. 

If only saturated fatty acids are present, stiff and rigid cell membranes or skin lipids are formed. In contrast to this, phosphohpids and ceramides with a high content of unsaturated fatty acids, such as linoleic acid or GLA, form stmctures which are more mobile and flexible. The result is an increase in the elastidly of the skin since unsaturated fatty acids are incorporated in the cell membranes of the skin. PUFA-nourished skin looks younger and smoother. 

---