**1. Introduction**

Coronary heart disease (CHD) is the leading cause of death worldwide, and certain dietary fatty acids (FAs) are known to play an important role in CHD risk [1]. It has been reported that higher intakes of industrially produced trans-fatty acids (IP-TFA) [2] and of saturated fatty acids (SFAs) are associated with increased risk for CHD [3, 4] and that higher intakes of both the omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and the omega-3 PUFAs are associated with lower risk of CHD [5, 6]. Intakes of the PUFAs (especially the omega-3 class) and IP-TFAs are considered to be biomarkers strongly

linked to risks. Because risk for CHD is much lower in Japan than in the US [7], we tried to compare the FA profiles in Japanese and American men over the age of 50.

### **1.1 Configurations of trans-fatty acids and their origins**

Trans-fatty acids have at least one double bond in the trans configuration and formed during partial hydrogenation of vegetable oils. This process is used for the conversion of vegetable oils to semisolid fats used for margarines.

Most of trans-fatty acids isomers are monosaturated with carbon number 18 (trans type octadecenoic acid (t-C18:1)). Trans type octadecenoic acids contained in foods are classified 13 isomers depending upon the location of the double bond (**Figure 1**). These trans isomers are produced industrially or naturally. The largest amounts of industrially produced trans-fatty acids are elaidic acids (t 9-C18:1) and those of naturally produced forms are vaccenic acid (t11-C18:1) [8].

In the cis forms of fatty acids, hydrogen atoms are present on the same side of the bond, which causes a bend in the fatty acid chain, whereas the trans form has hydrogen atoms in the opposite sides of the chain, which straightens the fatty acid chain (upper figure). There are many isomers in carbon 18 fatty acids. Elaidic acid has the double bond at the ninth carbon atom (t9-18:1). Oleic acid has the double bond at the same location (c9-18:1). Partially hydrogenated oils contain mixture of isomers in which the trans form may be detected anywhere between the 4th and 14th carbon. Smaller amounts of isomers with a second trans double bond (trans,trans-18:2) are also present.

**101**

**Figure 2.**

*Effects of trans-fatty acids.*

*Roles of Trans and ω Fatty Acids in Health; Special References to Their Differences…*

Fatty acids modulate cell functions. They change membrane fluidity and responses of membrane receptors. Fatty acids not only bind to membrane receptors but also bind to and modulate nuclear receptors that regulate gene transcription, peroxisome-proliferator-activated receptors, liver X receptor, and sterol regulatory element-binding protein 1 [9] (**Figure 2**). Fatty acids modulate metabolic and

Trans-fatty acids change the secretion, lipid composition, and the size of apoB100 produced by hepatic cells [11, 12]. In hepatocytes, trans-fatty acids increase the accumulation and secretion of free cholesterol and cholesterol esters [11]. Trans-fatty acids increase plasma activity of cholesteryl ester transfer protein [13], which may result in decreases in plasma levels of high density lipoprotein (HDL) and increase in the levels of low density lipoprotein (LDL) and very low

Trans-fatty acids modulate monocyte and macrophage functions resulting in increase in the production of tissue necrosis factor (TNF)-α and interleukin-6 [14]. Endothelial dysfunctions are caused by trans-fatty acids, and arterial dilatation is

Fatty acid metabolism of adipocytes was affected by trans-fatty acids, causing reduced triglyceride uptake, reduced esterification of cholesterol, and increased production of free fatty acids [16]. In animal studies, the gene expression was changed by the consumption of trans-fatty acids in adipocytes. These gene products are peroxisome-proliferator-activated receptor-γ, resistin, and lipoprotein lipase [17]. Trans-fatty acids may affect plasma lipid levels due to changes in hepatocytes of the production, secretion, and catabolism of lipoproteins and plasma levels of

*DOI: http://dx.doi.org/10.5772/intechopen.89551*

density lipoprotein (VLDL).

impaired due to nitric oxide [15].

**1.2 Molecular mechanisms of trans-fatty acids**

inflammatory responses of the endoplasmic reticulum [10].

**Figure 1.** *The configuration of cis and trans forms of the double bond.*

*Roles of Trans and ω Fatty Acids in Health; Special References to Their Differences… DOI: http://dx.doi.org/10.5772/intechopen.89551*

## **1.2 Molecular mechanisms of trans-fatty acids**

*Visions of Cardiomyocyte - Fundamental Concepts of Heart Life and Disease*

**1.1 Configurations of trans-fatty acids and their origins**

conversion of vegetable oils to semisolid fats used for margarines.

those of naturally produced forms are vaccenic acid (t11-C18:1) [8].

(trans,trans-18:2) are also present.

age of 50.

linked to risks. Because risk for CHD is much lower in Japan than in the US [7], we tried to compare the FA profiles in Japanese and American men over the

Trans-fatty acids have at least one double bond in the trans configuration and formed during partial hydrogenation of vegetable oils. This process is used for the

Most of trans-fatty acids isomers are monosaturated with carbon number 18 (trans type octadecenoic acid (t-C18:1)). Trans type octadecenoic acids contained in foods are classified 13 isomers depending upon the location of the double bond (**Figure 1**). These trans isomers are produced industrially or naturally. The largest amounts of industrially produced trans-fatty acids are elaidic acids (t 9-C18:1) and

In the cis forms of fatty acids, hydrogen atoms are present on the same side of the bond, which causes a bend in the fatty acid chain, whereas the trans form has hydrogen atoms in the opposite sides of the chain, which straightens the fatty acid chain (upper figure). There are many isomers in carbon 18 fatty acids. Elaidic acid has the double bond at the ninth carbon atom (t9-18:1). Oleic acid has the double bond at the same location (c9-18:1). Partially hydrogenated oils contain mixture of isomers in which the trans form may be detected anywhere between the 4th and 14th carbon. Smaller amounts of isomers with a second trans double bond

**100**

**Figure 1.**

*The configuration of cis and trans forms of the double bond.*

Fatty acids modulate cell functions. They change membrane fluidity and responses of membrane receptors. Fatty acids not only bind to membrane receptors but also bind to and modulate nuclear receptors that regulate gene transcription, peroxisome-proliferator-activated receptors, liver X receptor, and sterol regulatory element-binding protein 1 [9] (**Figure 2**). Fatty acids modulate metabolic and inflammatory responses of the endoplasmic reticulum [10].

Trans-fatty acids change the secretion, lipid composition, and the size of apoB100 produced by hepatic cells [11, 12]. In hepatocytes, trans-fatty acids increase the accumulation and secretion of free cholesterol and cholesterol esters [11]. Trans-fatty acids increase plasma activity of cholesteryl ester transfer protein [13], which may result in decreases in plasma levels of high density lipoprotein (HDL) and increase in the levels of low density lipoprotein (LDL) and very low density lipoprotein (VLDL).

Trans-fatty acids modulate monocyte and macrophage functions resulting in increase in the production of tissue necrosis factor (TNF)-α and interleukin-6 [14]. Endothelial dysfunctions are caused by trans-fatty acids, and arterial dilatation is impaired due to nitric oxide [15].

Fatty acid metabolism of adipocytes was affected by trans-fatty acids, causing reduced triglyceride uptake, reduced esterification of cholesterol, and increased production of free fatty acids [16]. In animal studies, the gene expression was changed by the consumption of trans-fatty acids in adipocytes. These gene products are peroxisome-proliferator-activated receptor-γ, resistin, and lipoprotein lipase [17].

Trans-fatty acids may affect plasma lipid levels due to changes in hepatocytes of the production, secretion, and catabolism of lipoproteins and plasma levels of

**Figure 2.** *Effects of trans-fatty acids.*

cholesteryl ester transfer protein (CETP) (upper left panel). In adipocytes, transfatty acids change fatty acid metabolism and, possibly, inflammatory responses. When trans fats are taken, nitric acid-dependent endothelial dysfunction is observed and circulating adhesion molecules increase. Trans fat modulates monocyte and macrophage function (lower left panel). Membrane receptors may affect subcellular mechanisms. These receptors localize with and are influenced by specific membrane phospholipids (upper right panel) such as endothelia nitric oxide synthetase or toll-like receptors. Trans-fatty acids may bind to nuclear receptorsregulating gene transcription such as liver X receptor (lower left panel).

#### **1.3 Effects on cardiovascular diseases**

Trans-fatty acids may increase the risks of coronary heart disease (CHD). In a meta-analysis of four prospective cohort studies, a 2% increase in energy intake from trans-fatty acids was shown to be associated with a 23% increase in the incidence of CHD [18–21].

There are many papers showing increased risks of CHD in patients with high fatty acids levels [22–25]. These data are obtained using cohorts of Western populations.

Koba et al. [26] recently reported using Japanese adult males that total transfatty acids levels were similar between acute coronary syndrome (ACS) and control subjects. Palmitelaidic acid levels were lower in ACS patients and were significantly directly associated with HDL cholesterol (HDL-C) and n-3 polyunsaturated FA (n-3 PUFA). Linoleic trans isomers (total C18:2 TFA) and primary industrially produced TFA (IP-TFAs) were significantly higher in ACS patients. Total trans-C18:1 isomers were comparable between ACS and control.
