**3. Results**

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

thrombosis. DHA may work in the similar ways as EPA.

tor) and TNF-α inflammatory signaling pathways [32].

ment of cardiovascular disease and diabetes mellitus.

(GLP-1), and increase insulin secretion by pancreas (**Figure 4**).

**1.6 ω fatty acid receptor**

**American old men**

**2.1 Materials and methods**

**2.2 Analyses of plasma samples**

chromatography as previously described.

**2.3 Statistical analysis**

*2.1.1 Participants*

EPA inhibits such processes, preventing cell damages, inflammation, and

GPR120 is proposed to function as an ω-3 FA receptor/sensor in pro-inflammatory macrophages and mature adipocytes. By signaling through GPR120, DHA and EPA mediate potent anti-inflammatory effects to inhibit both TLR (toll-like recep-

DHA and EPA stimulate GRP 120 and cause a decrease of glucose uptake by adipocytes, inhibit inflammation by macrophages, secrete glucagon-like peptide 1

**2. Differences of plasma levels of fatty acids between Japanese and** 

In Japan, we recruited 44 male volunteers older than 50. They were friends and

Fatty acids levels were measured in plasma obtained from ethylenediamine tetraacetic acid anticoagulated blood samples. Samples were frozen at −80°C until analyzed at Omegaquant, LLC (Sioux Falls, SD, USA). After thawing, an aliquot of plasma was combined (1.40 parts) with the methylating mixture (boron trifluoride in methanol [14%], toluene, and methanol [35/30/35, vv]), shaken at 100°C for 45 min. After cooling, 40 parts of both hexane and distilled water were added. After briefly vortexing, the samples were spun to separate layers, and an aliquot of the hexane layer that contained the fatty acid methyl esters was analyzed by gas

Student's t test was used for the comparison of two groups, and p < 0.05 was considered as significant difference. Results are expressed as mean ± SD. Spearman's

correlation tests were used to examine statistical significance.

family members of the research team for this study [33, 34]. Exclusion criteria included the use of medications to treat diabetes, hyperlipidemia, hypertension, and/or cardiovascular disease (CVD). Smokers were also excluded. The 76 US men were participants in the Chicago Area Sleep Study, a prospective cohort study to examine risk factors for the development of sleep disorders [35]. This cohort excluded men with known sleep disturbances but did not exclude for the chronic conditions excluded in the Japanese cohort. We collected blood samples after an overnight fast, and plasma was isolated for fatty acid analysis. We obtained an informed consent prior to conducting the protocol which had been approved by the Ethical Committee of Showa Women's University and Saiseikai Shibuya Satellite Clinic. The Chicago Area Sleep Study was approved by the Northwestern University Institutional Review Board.

These data suggest that DHA and EPA may be effective for prevention and treat-

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The ages of the two cohorts was reasonably similar (Japan, 61 ± 10 and US, 57 ± 5 years), as were the body mass indexes (24.9 ± 3.7 vs. 25.1 ± 3.4 kg/m2 ) (**Figure 5**).

Of the fatty acids that constituted at least 1% of the total in either cohorts, those that are significantly higher in Japanese men than US men were as follows: palmitic, palmitoleic, arachidic, EPA, and DHA. Those that were lower in the Japanese men were as follows: linoleic acid (LA), dihomo-gamma linolenic acid (DGLA), and AA (**Table 1**).

#### **Figure 5.**

*Profiles of plasma levels of fatty acids of Japanese and American old men.*


#### **Table 1.**

*Backgrounds of various parameters of healthy old men in Japan and US.*

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

**Figure 6** compares plasma levels of palmitoelaidic, elaidic, and linoelaidic acids. IP-TFAs (elaidic and mainly industrially produced linoelaidic),

although of low abundance in both cohorts, were considerably higher in the US than in Japan. Palmitoleic was slightly but significantly higher in Japan (**Figure 7**).

Plasma levels of DHA and EPA are higher in Japanese than American old men; on the other hand, plasma levels of arachidonic acid and dihomoγlinoleinic acid are higher in American than Japanese old men.

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American men.

*ss, statistical significance.*

*\* p < 0.05. \*\*p < 0.01.*

**Table 2.**

vitamins, etc.

**4.1 Results**

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

Stearic 7.0 ± 0.7 7.24 ± 0.83

Oleic 20.0 ± 2.6 19.96 ± 3.34

Arachidic 0.13 ± 0.04 0.13 ± 0.04

Eicosenoic 0.2 ± 0.04 0.15 ± 0.05 Alpha-linolenic 0.7 ± 0.2 0.72 ± 0.32

**Plasma fatty acids (% of total) Japanese (n = 44) US (n = 76) ss** Myristic 0.7 ± 0.2 0.85 ± 0.34 \*\* Palmitic 22.3 ± 1.3 21.23 ± 2.13 \* Palmitoelaidic (trans) 0.2 ± 0.1 0.14 ± 0.07 \*\* Palmitoleic 1.9 ± 0.6 1.45 ± 0.80 \*\*

Elaidic (trans) 0.1 ± 0.01 0.61 ± 0.34 \*\*

Linoelaidic (trans) 0.2 ± 0.1 0.35 ± 0.12 \*\* Linoleic (LA) 26.3 ± 4.0 32.83 ± 5.24 \*\*

Gamma linolenic 0.3 ± 0.1 0.53 ± 0.27 \*\*

Eicosadienoic 0.2 ± 0.03 0.29 ± 0.07 \*\* Behenic 0.15 ± 0.02 0.20 ± 0.10 \*\* Dihomo-gamma linolenic (DGLA) 1.0 ± 0.2 1.56 ± 0.37 \*\* Arachidonic (AA) 6.0 ± 1.1 7.38 ± 2.18 \*\* Eicosapentaenoic (EPA) 2.5 ± 1.3 0.77 ± 0.60 \*\* Lignoceric 0.22 ± 0.10 0.18 ± 0.07 \* Nervonic 0.33 ± 0.18 0.26 ± 0.10 \* Docosatetraenoic 0.12 ± 0.04 0.26 ± 0.11 \*\* Docosapentaenoic (n6) 0.14 ± 0.04 0.18 ± 0.08 \*\* Docosapentaenoic (n3) 0.68 ± 0.26 0.59 ± 0.14 \* Docosahexaenoic (DHA) 5.0 ± 1.5 2.14 ± 0.85 \*\*

**Table 2** summarizes plasma levels of important fatty acids between Japanese and

Participants were given self-administered diet history questionnaires and described answers on each item by recollection of diets they took (7 days dietary recall). We used a brief-type self-administered diet history questionnaire (BDHQ ) by using which the Japanese Ministry of Health, Labour and Welfare reports National Nutrition Surveys. From these questionnaires, we calculated the intakes of energy and varieties of foods such as proteins, carbohydrates, lipids

**Table 3** shows that only preference drinks such as tea and coffee had significant

correlations with plasma levels of palmitoelaidic acid and linoelaidic acid.

**4. Food intakes and plasma levels of fatty acids**

*Comparison of fatty acids profiles between Japanese and American men.*

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


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

#### **Table 2.**

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

higher in American than Japanese old men.

*Plasma levels of trans-fatty acids in Japanese and American old men.*

(**Figure 7**).

IP-TFAs (elaidic and mainly industrially produced linoelaidic), although of low abundance in both cohorts, were considerably higher in the US than in Japan. Palmitoleic was slightly but significantly higher in Japan

*Comparison of plasma levels of C20–22 fatty acids between Japanese and American old men.*

**Figure 6** compares plasma levels of palmitoelaidic, elaidic, and linoelaidic acids.

Plasma levels of DHA and EPA are higher in Japanese than American old men; on the other hand, plasma levels of arachidonic acid and dihomoγlinoleinic acid are

**106**

**Figure 7.**

**Figure 6.**

*Comparison of fatty acids profiles between Japanese and American men.*

**Table 2** summarizes plasma levels of important fatty acids between Japanese and American men.

### **4. Food intakes and plasma levels of fatty acids**

Participants were given self-administered diet history questionnaires and described answers on each item by recollection of diets they took (7 days dietary recall). We used a brief-type self-administered diet history questionnaire (BDHQ ) by using which the Japanese Ministry of Health, Labour and Welfare reports National Nutrition Surveys. From these questionnaires, we calculated the intakes of energy and varieties of foods such as proteins, carbohydrates, lipids vitamins, etc.

#### **4.1 Results**

**Table 3** shows that only preference drinks such as tea and coffee had significant correlations with plasma levels of palmitoelaidic acid and linoelaidic acid.

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


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and CHD.

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

tremendous impact to pathophysiology of cardiovascular system.

elucidate such differences between Japanese and American people.

Fatty acids are major components of blood vessels. So their changes exert

Epidemiological studies repeatedly showed that Japanese people had lower incidence of CVD, compared with American people [7]. As discussed below, kinds of intaken foods, life-styles, and genetics may contribute to such differences.

We thought the measurements of fatty acids composition in plasma may help to

We compared plasma levels of fatty acids between Japanese and American men over 50 years of age. We found, not surprisingly, that levels of EPA and DHA are higher in Japanese than American and that levels of arachidonic acid are lower in Japanese. Although both Japanese and American take meat, egg, and fish, fish has far more omega-3 fatty acids compared to eggs. When we eat larger amounts of omega-3 fatty acids such as DHA and EPA, omega-3 fatty acids are known to replace omega-6 fatty acids in cell membrane [36]. The omega-3 fatty acids are found predominantly in oily fish, whereas arachidonic acid (the major long chain omega-6 fatty acid) is contained in meats and eggs and can be synthesized (albeit very slowly) [37]. The differences between Japanese and US men in regard to the consumption of these types of foods can help explain these differences in blood levels [38]. The other major finding of this study was the lower levels of IP-TFA such

Currently, CHD death rates in Japan are 3× lower for women and 4× lower for men (ages 35–74) compared with the US. Among 30 countries for which the American Heart Association provided CHD death rates in its 2017 Statistical Update [7], Japan had the second and third lowest rates (men and women, respectively) compared with the US. Sekikawa et al. [39] showed in 2014 that the calcification of the coronary artery was twice in American compared with Japanese men, but the calcification of Hawaiian Japanese was similar to that of

These results do not necessarily prove differences of CVD incidences between Japanese and American are due to foods and lifestyle. Since Japanese immigrants to the US have increased CHD mortality [40], although still lower US Whites, it appears that some genetic variabilities between American and Japanese must be responsible for this difference. However, the possibility that differences in dietary fatty acid patterns may contribute to this phenomenon is the subject of this report. We found that the levels of the long-chain omega-3 fatty acids such as EPA and DHA were 2–3× higher in Japan vs. the US. The relationship of fish and dietary omega-3 fatty acids and cardiovascular disease (CVD) has been investigated in numerous studies and comprehensive reviews and recommendations exist. Still controversies exist. A recent meta-analysis of randomized trials with omega-3 fatty acids [41] did not find a statistically significant reduction in CVD mortality, but in these researches, some important factors were said to be ignored [42–44]. Other systematic reviews have reported mortality benefits for omega-3 fatty acids [45, 46], and omega-3 biomarker levels have been strongly associated with risk for fatal CHD in still other meta-analyses [47, 48]. Hence, higher omega-3 levels could at

We also found that IP-trans-fatty acid such as linoelaidic acid was lower in Japan than US. The reported intake of IP-TFA is 75% lower in Japan than in the US, again supporting the observed differences in biomarker levels. Circulating 18:2 trans-fatty acids was shown to be most adversely associated with total mortality, mainly due to the increased risk of CVD [23]. It was also positively associated with total mortality

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

as linoelaidic acid in Japanese vs. the US men.

least partly explain the lower CHD risk in Japan.

people on the US mainland.

**5. Discussion**

#### **Table 3.**

*Correlations between foods intake and plasma levels of fatty acids.*

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