**2. Role of polyunsaturated fatty acids**

Polyunsaturated fatty acids (PUFAs) are components of the lipid bilayer of cell membranes, where they also regulate membrane fluidity. Cell membranes containing more saturated fatty acids and cholesterol are more rigid, while PUFAs increase their fluidity as well as the number of receptors and their affinity to their substrates, like hormones and growth factors (Das, 2006).

PUFAs are also precursors of several second messengers. From the n-6 group, especially from AA proinflammatory eicosanoids are synthesized, while the n-3 fatty acids, especially eicosapentaenoic acid (C20:5n-3, EPA) are precursors of antiinflammatory eicosanoids.

The n-6 essential fatty acid (EFA), LA plays an important role in the maintenance of the epidermal water barrier (Koletzko & Rodriguez-Palmero, 1999), preventing thereby the transepidermal water loss and epidermal damage (Yen et al., 2008). There are data indicating that LA also lowers plasma total cholesterol levels (Nikkari et al., 1983). In an animal study the n-3 EFA, ALA lowered serum and liver triacylglycerol levels, while it increased serum HDL-cholesterol levels (Murano et al., 2007).

AA and DHA play an important role in the maturation of the developing nervous system: during the third trimester and in the first months of life there is an increased incorporation into the fetal/neonatal brain and retinal membranes (Farquharson et al., 1992; Martinez & Mougan, 1998).

Fish oil, containing EPA and DHA, may be beneficial not only during infancy, but also during adulthood. It may prevent the development of macula degeneration (Chua et al.,

Fatty Acid Supply in Pregnant Women with Type 1 Diabetes Mellitus 439

have indicated, that *trans* fatty acids may disturb the metabolism of the physiologically

important n-3 and n-6 fatty acids (Szabó et al, 2007, 2010a; Vidgren et al., 1998).

figure modified from http://www.lpi.oregonstate.edu; source of fatty acid figures:

The n-3 EFA, ALA is found in the highest quantity in linseed oil, and considerable amounts are found in hempseed oil (20%) as well (Erasmus, 1993); however, from the dietary point of view its most important sources are walnut and rapeseed oils (Beare-Rogers et al., 2001). The n-6 EFA, LA can be found in the highest proportion in primrose (81%; Erasmus, 1993) and grapeseed oils, but its most important dietary sources are sunflower, corn and pumpkin seed oils (Table 1; Beare-Rogers et al., 2001). Compared to vegetable sources, animal lipid

Flesh of herbivorous animals is very rich in the most important n-6 metabolite, AA (Table 2). On the other hand, haslets of terrestrial animals, like liver and kidney contains DHA also in

The most important n-3 LCPUFAs, EPA and DHA can be found in fatty sea fishes (Table 3). The DHA content of sea fishes may vary according to season, area of catching and to age and gender of the fish (Racine & Deckelbaum, 2007). Marine fish contains higher levels of n-3 PUFAs, EPA and DHA, while lower n-6 PUFAs, LA and AA compared to freshwater species. In a Chinese study, the edible meat of cultured freshwater fish contained more n-3

Fig. 1. Metabolism of n-6 and n-3 fatty acids

sources contain smaller quantities of ALA and LA (Table 2).

http://www.3dchem.com/index.asp

**2.2 Dietary sources of fatty acids** 

relative high concentrations.

2006), may lower the risk of developing dementia and Alzheimer-disease (Morris et al., 2003; Schaefer et al., 2006) and may be beneficial in bipolar depression (Noaghiul & Hibbeln, 2003). N-3 LCPUFAs play also an important role in the prevention of cardiovascular diseases: fish oil supplementation increased HDL-cholesterol levels, while decreased triacylglycerol levels (Laidlaw & Holub, 2003), reduced the progression of atherosclerosis (Erkkilä et al., 2004), the risk of coronary heart disease (Iso et al., 2006; Mozaffarian et al., 2005), fatal myocardial infarction (Yuan et al., 2001), sudden cardial death (Albert et al., 1998), incidence of atrial fibrillation (Mozaffarian et al., 2004) and the risk of stroke (Mozaffarian et al., 2005). In a longitudinal, observational study, fish oil supplementation reduced the risk of developing islet autoimmunity in children at increased genetic risk for T1DM (Norris et al, 2007).

*Trans* isomeric fatty acids increase serum lipoprotein(a), LDL-cholesterol, triacylglycerol (Katan et al., 1995) and total cholesterol levels (Louheranta et al., 1999), as well as significantly decrease the levels of HDL-cholesterol (Dyerberg et al., 2004; Louheranta et al., 1999; Sun et al., 2007); in summary, they increase the risk of cardiovascular diseases (Sun et al., 2007). In an animal study rats fed with *trans* fatty acid diet (similar to saturated fatty acid diet) had high levels of fasting plasma insulin and decreased adipocyte insulin sensitivity (Ibrahim et al., 2005). In contrast, in a human study *trans* fatty acid diet did not alter insulin sensitivity (Louheranta et al., 1999).

#### **2.1 Biochemistry of fatty acids**

The physiologically most important PUFAs contain 2-6 double bonds and have a chain length of 18, 20 or 22 carbon atom. The methyl end of the molecule is called the omega end. On the basis of the distance of the first double bond from the carbon atom at the omega end, three different groups of fatty acids can be distinguished: omega-3 (n-3), omega-6 (n-6) and omega-9 (n-9) fatty acids.

The human body is unable to establish double bond in the n-3 and n-6 position, so we have to ingest the EFAs, the n-3 ALA and n-6 LA with our diet. The most important dietary sources of these fatty acids are vegetables and vegetable oils.

From the essential n-6 LA, after -6 desaturation γ-linolenic acid (C18:3n-6, GLA) and after elongation dihomo-γ-linolenic acid (C20:3n-6, DHGLA) is synthesised. After a -6 desaturational step, the most important metabolite, AA is produced (Fig. 1).

The metabolism of the n-3 group is a longer, more complicated process. After elongation, -5 and -6 desaturation eicosapentaenoic acid (C20:5n-3, EPA) is formed. After chain elongation docosapentaenoic acid (C22:5n-3, DPA) is synthesised. The most important n-3 metabolite, DHA is produced after -6 desaturation and peroxisomal β-oxidation (Fig. 1).

Although the same enzymes are involved into the metabolism of the n-3 and n-6 group, these fatty acids cannot be transformed into each other, because the molecule can only be activated from the carboxyl end. In the metabolism, the elongation is a quicker, while desaturation is a slower step, so these desaturational steps determine the speed of metabolism (i.e. these are the rate-limiting steps).

In the nature, PUFAs can be found predominantly as cis isomers, while *trans* fatty acids are produced in the stomach of ruminants and during the partial hydrogenation of vegetable oils. Cis double bond bends the molecule, while *trans* double bond straightens the fatty acid, so it is similar to saturated fatty acids. From this difference arise their different physiological effects: *trans* isomers are similar to saturated fatty acids, while cis isomers have more beneficial effects. As cis and *trans* fatty acids use the same enzymes during their metabolism, several studies

2006), may lower the risk of developing dementia and Alzheimer-disease (Morris et al., 2003; Schaefer et al., 2006) and may be beneficial in bipolar depression (Noaghiul & Hibbeln, 2003). N-3 LCPUFAs play also an important role in the prevention of cardiovascular diseases: fish oil supplementation increased HDL-cholesterol levels, while decreased triacylglycerol levels (Laidlaw & Holub, 2003), reduced the progression of atherosclerosis (Erkkilä et al., 2004), the risk of coronary heart disease (Iso et al., 2006; Mozaffarian et al., 2005), fatal myocardial infarction (Yuan et al., 2001), sudden cardial death (Albert et al., 1998), incidence of atrial fibrillation (Mozaffarian et al., 2004) and the risk of stroke (Mozaffarian et al., 2005). In a longitudinal, observational study, fish oil supplementation reduced the risk of developing islet autoimmunity in children at increased genetic risk for

*Trans* isomeric fatty acids increase serum lipoprotein(a), LDL-cholesterol, triacylglycerol (Katan et al., 1995) and total cholesterol levels (Louheranta et al., 1999), as well as significantly decrease the levels of HDL-cholesterol (Dyerberg et al., 2004; Louheranta et al., 1999; Sun et al., 2007); in summary, they increase the risk of cardiovascular diseases (Sun et al., 2007). In an animal study rats fed with *trans* fatty acid diet (similar to saturated fatty acid diet) had high levels of fasting plasma insulin and decreased adipocyte insulin sensitivity (Ibrahim et al., 2005). In contrast, in a human study *trans* fatty acid diet did not alter insulin

The physiologically most important PUFAs contain 2-6 double bonds and have a chain length of 18, 20 or 22 carbon atom. The methyl end of the molecule is called the omega end. On the basis of the distance of the first double bond from the carbon atom at the omega end, three different groups of fatty acids can be distinguished: omega-3 (n-3), omega-6 (n-6) and

The human body is unable to establish double bond in the n-3 and n-6 position, so we have to ingest the EFAs, the n-3 ALA and n-6 LA with our diet. The most important dietary

From the essential n-6 LA, after -6 desaturation γ-linolenic acid (C18:3n-6, GLA) and after elongation dihomo-γ-linolenic acid (C20:3n-6, DHGLA) is synthesised. After a -6

The metabolism of the n-3 group is a longer, more complicated process. After elongation, -5 and -6 desaturation eicosapentaenoic acid (C20:5n-3, EPA) is formed. After chain elongation docosapentaenoic acid (C22:5n-3, DPA) is synthesised. The most important n-3 metabolite, DHA is produced after -6 desaturation and peroxisomal β-oxidation (Fig. 1). Although the same enzymes are involved into the metabolism of the n-3 and n-6 group, these fatty acids cannot be transformed into each other, because the molecule can only be activated from the carboxyl end. In the metabolism, the elongation is a quicker, while desaturation is a slower step, so these desaturational steps determine the speed of

In the nature, PUFAs can be found predominantly as cis isomers, while *trans* fatty acids are produced in the stomach of ruminants and during the partial hydrogenation of vegetable oils. Cis double bond bends the molecule, while *trans* double bond straightens the fatty acid, so it is similar to saturated fatty acids. From this difference arise their different physiological effects: *trans* isomers are similar to saturated fatty acids, while cis isomers have more beneficial effects. As cis and *trans* fatty acids use the same enzymes during their metabolism, several studies

sources of these fatty acids are vegetables and vegetable oils.

metabolism (i.e. these are the rate-limiting steps).

desaturational step, the most important metabolite, AA is produced (Fig. 1).

T1DM (Norris et al, 2007).

sensitivity (Louheranta et al., 1999).

**2.1 Biochemistry of fatty acids** 

omega-9 (n-9) fatty acids.

have indicated, that *trans* fatty acids may disturb the metabolism of the physiologically important n-3 and n-6 fatty acids (Szabó et al, 2007, 2010a; Vidgren et al., 1998).

Fig. 1. Metabolism of n-6 and n-3 fatty acids figure modified from http://www.lpi.oregonstate.edu; source of fatty acid figures: http://www.3dchem.com/index.asp
