**Fatty Acids and Emotional Behavior**

Carlos M. Contreras1,2, Ana G. Gutiérrez-García2,3 and Diana Idania Vásquez-Hernández2 *1Unidad Periférica Xalapa, Instituto de Investigaciones Biomédicas, Universidad Nacional, Autónoma de México, Xalapa, Veracruz, 2 Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, 3 Facultad de Psicología,Universidad Veracruzana, Xalapa, Veracruz, Mexico* 

#### **1. Introduction**

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Fatty acids are widely distributed in nature. In addition to being found in plants and seeds, these organic compounds are present in other organisms, from unicellular protists to mammals, including humans. The anabolic and catabolic pathways of fatty acids have been identified. They have a well-known function as energy sources in metabolic processes and constitute a fundamental part of cellular membrane structures. Long-chain fatty acids also play a role in inflammatory process. Fatty acids exert their actions by modifying the fluidity of membranes, exerting marked actions on membrane ionic channels, and leading to a reduction in the excitability of cardiac myocytes, thus prompting interest in the study of fatty acids as protectors of cardiac function. Fatty acids exert similar actions on membrane neurons and the modulation of neurotransmission. The role of fatty acids in several psychiatric and neurologic conditions is a topic of current research. Fatty acid deficiency appears to be related to alterations in development, but the results from supplementary diet studies are far from conclusive. Interestingly, fatty acids are present in amniotic fluid, colostrum, and maternal milk in at least two mammalian species (i.e., pigs and humans) and according to both anecdotal and experimental reports appear to produce anxiolytic effects. Additionally, fatty acids exert effects when applied by the olfactory route. Odorant carrier proteins to olfactory receptors are present in maternal fluids and nasal mucosa epithelia. In newborns, fatty acids may also act as olfactory cues for feeding source seeking after exposure during prenatal life, which may constitute an additional function.

#### **2. Overview**

Lipids are organic compounds that are insoluble in water but soluble in nonpolar solvents, such as ether and chloroform. Some of these lipids naturally occur in the marine food chain. From an evolutionary ecological perspective, their presence in dinoflagelates, teleosts, amphibians, reptiles, birds, mammalians, and humans is important (Crawford et al., 2009).

Fatty Acids and Emotional Behavior 111

The physical properties of fatty acids are related to the length of their carbon chain and unsaturation. The nonpolar characteristics of the hydrocarbon chain explain the poor solubility of fatty acids in water. The polar carboxylic acid group (ionized at neutral pH) explains the poor solubility of short-chain fatty acids in water (Berg et al., 2003; Nelson & Cox, 2005). Likewise, longer chains have a higher melting point. Unsaturated fatty acids have a melting point that is lower than that of saturated fatty acids of the same length (Berg

The biotransformation process of fatty acids has been summarized by Nelson and Cox (2005). The synthesis of fatty acids may occur by *de novo* synthesis or modification of the carbon chain (Gurr et al., 2002). In *de novo* synthesis, fatty acids are synthesized from pyruvate, the final product of glycolysis, with the participation of a three-carbon intermediary and malonyl-CoA, an irreversible catalytic product of acetyl-CoA (Gurr et al.,

The assembly of the carbon chains of fatty acids occurs through a four-step sequence. A saturated acyl group is the substrate for subsequent condensation with an activated malonyl group. With each step of the cycle, the acyl chain is extended by two carbons. The cycle is completed with the formation of a chain of 16 carbons (i.e., palmitic acid [C16:0], an SFA). Carbons C-16 and C-15 from palmitic acid are derived from the carboxyl and methyl carbons, respectively, of an acetyl-CoA. Other carbons are derived from acetyl-CoA via malonyl-CoA. NADPH acts as a reducing agent, and the two SH groups that are bound to the enzyme are the active group. All reactions in the synthesis are catalyzed by a

Palmitic acid is the terminal product in fatty acid synthesis in animal cells and is the precursor SFA and MUFA through elongation of the carbon chain. Palmitic acid (16:0) can be elongated to form stearate (18:0) or a longer carbon chain through the addition of acetyl groups with the participation of elongase enzymes. The process occurs via two elongation systems located in the mitochondria and smooth endoplasmic reticulum from the liver,

One of the most important functions of elongation is the conversion of essential fatty acids into PUFA (Gurr et al., 2002). However, these fatty acids cannot be synthesized by mammalian cells and must be obtained from the diet as linoleic acid (18:2) and -linolenic acid (18:3) to be transformed into PUFA, such as dihomo--linolenic acid (18:3), arachidonic acid (20:4), eicosapentaenoic acid (20:5), and docosahexaenoic acid (DHA; 22:6; Haggarty,

A second mechanism for the synthesis of fatty acids is desaturation (Gurr et al., 2002). Palmitic acid and stearic acid serve as the precursors of two of the most common MUFA in animal tissues (i.e., palmitoleic acid [16:1] and oleic acid [18:1]), which have a *cis* doublebond between C-9 and C-10. The double-bond is introduced into the fatty acid chain by an oxidative reaction with the participation of O2, NADH, and three proteins: cytochrome b5, a

**2.3 Physical and chemical properties** 

et al., 2003; Nelson & Cox, 2005).

multienzymatic complex, fatty acid synthase.

brain, and some other tissues (Gurr et al., 2002).

**2.4 Anabolic processes** 

2002).

2002).

In mammals, the highest lipid concentrations occur in adipose tissue, followed by the central nervous system (Carrié et al., 2000). However, lipids are present in all cell types, where they contribute to cell structure and energy storage and participate in many biological processes, such as gene transcription, the regulation of metabolic pathways, and other physiological processes (Gurr et al., 2002).

The biological functions of lipids are as diverse as their chemistry. Fats and oils are the main forms of energy storage in many organisms, and phospholipids and sterols are the major structural elements of biological membranes. Other lipids, although present in relatively small amounts, play a crucial role in the composition of enzymatic cofactors, electron carriers, light pigments, membrane protein folding, digestive tract emulsifiers, hormones, and intracellular messengers (Nelson & Cox, 2005). Fatty acids are the main component of phospholipids, triglycerides, and cholesterol esters (Agostoni & Bruzzese, 1992).

#### **2.1 Definition and classification**

Fatty acids are aliphatic carboxylic acids composed of four to 36 carbon chains and a variable degree of unsaturation, ending in a carboxyl group (Berg et al., 2003; Nelson & Cox, 2005). The moiety of carbon chains can be short (2-4 carbons), medium (6-12 carbons), long (14-18 carbons), and very long (derived from 18 carbon molecules; Agostoni & Bruzzese, 1992). The hydrocarbon chain can be saturated or may have one or more double unsaturated bonds (Bézard et al., 1994). Based on the number of unstaurations, the hydrocarbon chain may constitute monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA; Agostoni & Bruzzese, 1992; Bézard et al., 1994). The classification of PUFA is based on the location of the last double-bond near the methyl end, yielding the typical location n-3 or n-6. However, mammals cannot introduce double-bonds between C-9 and the methyl end of fatty acids; thus, mammals are not able to synthesize n-3 or n-6 PUFA or convert n-3 PUFAs into n-6 PUFAs or vice versa (Bézard et al., 1994; Colin et al., 2003; Dobryniewski et al., 2007). Instead, n-3 and n-6 PUFA are derived from other fatty acids that act as precursors (Stulnig, 2003). n-3 and n-6 PUFA can be synthesized from the precursors linoleic acid (18:2) and -linolenic acid (18:3), which in turn may be synthesized from shorter-chain fatty acids, such as palmitic acid (C16:0; Cunnane et al., 1995). Similarly, saturated fatty acids (SFA) and MUFA can be synthesized from acetate precursors (e.g., carbohydrates, glycogenic amino acids) and PUFA (Brenna et al., 2009).

#### **2.2 General properties**

Fatty acids are esters in natural fats and oils but also exist in non-esterified forms, such as free fatty acids, that circulate in the blood of vertebrates via noncovalent bonds with the carrier protein serum albumin. Typically, the most abundant fatty acids have carbon chains from 14 to 24 atoms, although the most abundant fatty acids contain 16 to 18 atoms. In nature, the most abundant are unsaturated fatty acids, followed by saturated, with doublebonds and a *cis* configuration (Berg et al., 2003; Nelson & Cox, 2005). The *cis* configuration can be converted to the *trans* form by catalytic heating. Saturated fatty acids are very stable, whereas unsaturated acids are susceptible to oxidation (i.e., the more double-bonds, the higher susceptibility to oxidation; Gurr et al., 2002).

In mammals, the highest lipid concentrations occur in adipose tissue, followed by the central nervous system (Carrié et al., 2000). However, lipids are present in all cell types, where they contribute to cell structure and energy storage and participate in many biological processes, such as gene transcription, the regulation of metabolic pathways, and

The biological functions of lipids are as diverse as their chemistry. Fats and oils are the main forms of energy storage in many organisms, and phospholipids and sterols are the major structural elements of biological membranes. Other lipids, although present in relatively small amounts, play a crucial role in the composition of enzymatic cofactors, electron carriers, light pigments, membrane protein folding, digestive tract emulsifiers, hormones, and intracellular messengers (Nelson & Cox, 2005). Fatty acids are the main component of

Fatty acids are aliphatic carboxylic acids composed of four to 36 carbon chains and a variable degree of unsaturation, ending in a carboxyl group (Berg et al., 2003; Nelson & Cox, 2005). The moiety of carbon chains can be short (2-4 carbons), medium (6-12 carbons), long (14-18 carbons), and very long (derived from 18 carbon molecules; Agostoni & Bruzzese, 1992). The hydrocarbon chain can be saturated or may have one or more double unsaturated bonds (Bézard et al., 1994). Based on the number of unstaurations, the hydrocarbon chain may constitute monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA; Agostoni & Bruzzese, 1992; Bézard et al., 1994). The classification of PUFA is based on the location of the last double-bond near the methyl end, yielding the typical location n-3 or n-6. However, mammals cannot introduce double-bonds between C-9 and the methyl end of fatty acids; thus, mammals are not able to synthesize n-3 or n-6 PUFA or convert n-3 PUFAs into n-6 PUFAs or vice versa (Bézard et al., 1994; Colin et al., 2003; Dobryniewski et al., 2007). Instead, n-3 and n-6 PUFA are derived from other fatty acids that act as precursors (Stulnig, 2003). n-3 and n-6 PUFA can be synthesized from the precursors linoleic acid (18:2) and -linolenic acid (18:3), which in turn may be synthesized from shorter-chain fatty acids, such as palmitic acid (C16:0; Cunnane et al., 1995). Similarly, saturated fatty acids (SFA) and MUFA can be synthesized from acetate precursors (e.g., carbohydrates, glycogenic amino

Fatty acids are esters in natural fats and oils but also exist in non-esterified forms, such as free fatty acids, that circulate in the blood of vertebrates via noncovalent bonds with the carrier protein serum albumin. Typically, the most abundant fatty acids have carbon chains from 14 to 24 atoms, although the most abundant fatty acids contain 16 to 18 atoms. In nature, the most abundant are unsaturated fatty acids, followed by saturated, with doublebonds and a *cis* configuration (Berg et al., 2003; Nelson & Cox, 2005). The *cis* configuration can be converted to the *trans* form by catalytic heating. Saturated fatty acids are very stable, whereas unsaturated acids are susceptible to oxidation (i.e., the more double-bonds, the

phospholipids, triglycerides, and cholesterol esters (Agostoni & Bruzzese, 1992).

other physiological processes (Gurr et al., 2002).

**2.1 Definition and classification** 

acids) and PUFA (Brenna et al., 2009).

higher susceptibility to oxidation; Gurr et al., 2002).

**2.2 General properties** 

### **2.3 Physical and chemical properties**

The physical properties of fatty acids are related to the length of their carbon chain and unsaturation. The nonpolar characteristics of the hydrocarbon chain explain the poor solubility of fatty acids in water. The polar carboxylic acid group (ionized at neutral pH) explains the poor solubility of short-chain fatty acids in water (Berg et al., 2003; Nelson & Cox, 2005). Likewise, longer chains have a higher melting point. Unsaturated fatty acids have a melting point that is lower than that of saturated fatty acids of the same length (Berg et al., 2003; Nelson & Cox, 2005).
