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Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats' Heart and Dyslipidemia a
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Madiha Dhibi PhD , Amira Mnari PhD , Faten Brahmi PhD , Zohra Houas Pr , Issam Chargui b
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PhD , Wafa Kharroubi PhD & Mohamed Hammami Pr
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Laboratory of Nutrition-Functional Foods and Vascular Health, Faculty of Medicine, University of Monastir, Monastir, TUNISIA b
Laboratory of Histology Cytology and Genetics, Faculty of Medicine, University of Monastir, Monastir, TUNISIA Published online: 20 Mar 2015.
Click for updates To cite this article: Madiha Dhibi PhD, Amira Mnari PhD, Faten Brahmi PhD, Zohra Houas Pr, Issam Chargui PhD, Wafa Kharroubi PhD & Mohamed Hammami Pr (2015): Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats' Heart and Dyslipidemia, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2014.938183 To link to this article: http://dx.doi.org/10.1080/07315724.2014.938183
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Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats’ Heart and Dyslipidemia
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Madiha Dhibi, PhD, Amira Mnari, PhD, Faten Brahmi, PhD, Zohra Houas, Pr, Issam Chargui, PhD, Wafa Kharroubi, PhD, Mohamed Hammami, Pr Laboratory of Nutrition-Functional Foods and Vascular Health (M.D., A.M., F.B., W.K., M.H.), Laboratory of Histology Cytology and Genetics (Z.H., I.C.), Faculty of Medicine, University of Monastir, Monastir, TUNISIA Key words: trans-fatty acids, high-fat diet, cardiovascular disease, rats Objectives: A direct effect of process-induced trans-fatty acids (TFAs) on nonalcoholic fatty liver disease (NAFLD) as a cardiovascular disease (CVD) risk factor has previously been shown. We hypothesized that TFAs directly induced CVD. This article describes an investigation of the association between TFAs, provided by the consumption of oxidized soybean oil and margarine, and plasma lipid profiles, coronary artery lesions, and coronary fatty acids distribution in rats. Male rats were fed a standard chow or high-fat diet containing different TFA levels ranging from SO.
DISCUSSION The different types of diet were designed to be isoenergetic; therefore, each variation is due to the type of fat used. Daily
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feed intake and body weight gain throughout the experiment did not differ among experimental groups. Differences in the dietary FA composition induce differences in their deposition into the rats’ hearts. The relative levels of the total SFAs were not altered by high-fat diet. Our study showed that in rats, the food intake of PUFAs increase the level of this endogenous fraction in the heart, reflecting the accurate incorporation of these FAs depending to level importance in each diet as follows: SO > OSO > MG (Table 3). Fatty acids play an essential role in cellular metabolism as powerful modulators of cell membrane receptors and affect signal transduction, gene transcription, and eicosanoid metabolism [10] and in the physiological responses of cells by regulating membrane fluidity [11]. In fact, the role of FA oxidation is controversial. On one hand, FA oxidation is viewed as a protective mechanism for the disposal of potentially toxic free FAs but, on the other hand, increased oxidation of FAs can generate reactive oxygen species, which cause tissue damage [12]. Elevated levels of FAs are known to cause the production of reactive oxygen species and oxidative stress [13,14]. Lipid oxidation reactions proceed through the same basic mechanisms of lipid hydroperoxide formation and decomposition in biological systems and in foods [15]. Single hydroperoxide isomers are not stable but are readily isomerized to an equilibrium mixture of geometrical and positional hydroperoxide isomers [16,17]. In our previous study, we demonstrated that dietary trans-fat increases liver lipid peroxidation [5]. Fat oxidation might be influenced by the degree of unsaturation of FAs, in the order linolenic > linoleic > oleic [18]. Linoleic acid as omega-6 FA has been traditionally considered heart healthy [19]. However, in recent years, questions have been raised as to whether the consumption of linoleic acid has become excessive [20], to the point of actually contributing to an increased risk for coronary heart disease (CHD) via its conversion to arachidonic acid, the predominant substrate for proinflammatory prostaglandins, leukotrienes, thromboxane, and prostacyclin [21]. Dlouhy et al. [22] demonstrated that higher linoleic acid intakes tend to decrease serum LDL-C levels, which cannot be explained by our results because the MG diet with lower linoleic acid content reveale a significant increase in LDL-C. It is assumed that industrial trans-fats increase LDL-C, which is confirmed in this study by the MG diet, which significantly increased LDLC. Our findings clearly show that rats with hyperlipidemia induced by a high-fat feed exhibit trans-FA accumulation in their hearts. A positive correlation between total TFAs in diet and relative trans-isomers in the hearts of rats receiving these diets was observed (r D 0.965; p < 0.05). Hence, after feeding high-fat diets containing different levels of trans-fats for 4 weeks, the rats showed differently deposited trans-isomers in their hearts. Elaidic acid, which has been previously shown to be incorporated in many tissues [23], is known to accumulate in atherosclerotic lesions and is associated with increased risk of CHD [24,25] and was markedly increased in the hearts
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Trans-Fatty Acids and Dyslipidemia
Fig. 2. Histological aspects of coronary arteries sections from control rats and rats fed high-fat diets. Normal artery histological aspect from a control: (A) and (B): H&E 32£ and 100£, respectively. Arteries from SO group: (C) and (D): H&E 32£ and 100£, respectively. Arteries from MG group: (E), (F), and (G): H&E 32£ and 100£, respectively. Black triangle indicates wall thickness. White triangle indicates lumen reduction. Black arrows show fat deposit. White arrows show media calcification.
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Trans-Fatty Acids and Dyslipidemia
Fig. 3. Histological aspects of coronary veins sections from control rats and rats fed a high-fat diet (H&E 32£). (a) Normal vein histological aspect from a control: (b) vein from SO group; (c) vein from OSO group; and (d) vein from MG group. Black triangle indicates wall thickness. White triangle indicates lumen reduction. Thin arrows show fat deposit.
of MG-fed rats compared to other groups. It has been previously reported that monounsaturated TFA isomers with 18-carbon chain length (trans-18:1), which comprise about 85% of the total TFA in foods [26], are some of the predominant TFAs present in the human diet [27,28]. A previous report was published showing that intake of trans-18:1 raised the LDL/HDLC level ratio in comparison with cis-18:1 [29]. Unlike transisomers of MUFA, trans-PUFA, essentially as trans-18:2 isomers, was detected in rats’ hearts in all experimental groups with relatively high levels in the MG group, although the predominant trans-isomer in the MG diet was the elaidic acid. trans-PUFA could be formed in vivo by desaturation of trans18:1 present in the diet. Supplementing the diet with oxidized oil resulted in relatively higher levels of heart trans-18:3 n3 in the OSO group than in the controls, and in SO and MG groups corresponding to their intake from the diet. Grandgirard et al. [28] have suggested that the pathways used to synthesize the trans long-chain n-3 PUFA are similar to those of the corresponding cis compounds but that the rate of conversion could be different. Trans-PUFA have been reported to have adverse effects on the plasma lipid profile compared to their cis-isomers [31]. Anderson et al. [30] and Beyers et al. [31] had shown that the position of the trans double bond in the 18:2 acid appears to influence its metabolic fate and incorporation into tissue lipids. Trans-18:2 isomers have been found to be more adversely related to CHD risk than are trans-18:1 [34– 36]. A possible explanation for these adverse effects on CVD
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is that trans-18:2 isomers are incorporated in the sn-2 position of phospholipids, where PUFAs are usually found [37]. This substitution might affect membrane properties and have effects on atherosclerotic pathways through increased macrophage adhesion [37,38]. In the present study, consumption of the 3 types of high-fat diets stimulated changes in plasma lipid markers. Plasma TG concentrations were significantly greater in the trans-fed rats than in the control rats. Trans-fats increase levels of TG compared to the intake of other fats [22,39]. Increased dietary intake of TFAs has been associated with deleterious effect on plasma TGs. Khan-Merchant et al. [41] suggested that animals fed a nonatherogenic diet did not develop atherosclerosis even in the presence of oxidized FAs. In the present study, oxidized oil increases TG and TC, which can be attributed to the TFA content in the oxidized oil compared to the fresh oil. This assumption was supported by the significant positive correlation between TFAs in the diet and circulating TG (r D 0.986; p < 0.05; Table 4). Rats fed a high-fat diet had hypercholesterolemia that differs depending to trans-isomers level, showing a close correlation with TFA levels in their diets (r D 0.978; p < 0.05). Although these effects would be expected to increase the risk of CVD, the relation between the intake of trans-fats and the incidence of CVD reported in prospective studies has been greater than that predicted by changes in circulating lipid levels alone [41]. It has been suggested that the process of atherosclerosis, which is fundamental to the occurrence of cardiovascular disease, is recognized as a
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Trans-Fatty Acids and Dyslipidemia Table 4. Pearson’s Correlations Assessed between TFA Levels in Diet and in Heart and Plasma Lipid Markers of Experimental Rats
TFAdiet TFAheart TC TG HDL LDL LDL/HDL ratio
TFAdiet
TFAheart
TC
TG
HDL
LDL
LDL/HDL Ratio
1 0.956* 0.978* 0.986* ¡0.920 0.987* 0.987*
1 0.979* 0.916 ¡0.885 0.966* 0.970*
1 0.971* ¡0.958* 0.997** 0.998**
1 ¡0.962* 0.986* 0.984*
1 ¡0.964* ¡0.962
1 1.000***
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TFA D trans-fatty acids, TC D total cholesterol, TG D triglycerides, HDL D high-density lipoprotein, LDL D low-density lipoprotein. Data are presented as r values. * p < 0.05. **p < 0.01. ***p < 0.001.
consequence of the interplay of a plethora of genetic and environmental factors, but lipoproteins remain the foundation of its pathogenesis [2]. In this study, plasma lipoprotein profiles were significantly affected by high-fat diets. It is assumed that industrial trans-fats increase LDL-C in a similar manner as saturated fat but, unlike saturated fat, it also decreases HDL-C. The association between the intake of TFAs and CHD has often been attributed to the impact of TFAs on plasma biomarkers for CHD risk, specifically, increases in concentrations of TC and LDL-C along with decreases in HDL-C [42]. Hence, the decrease in HDL-C in groups fed diets rich in different TFAs seems to be significant in the OSO and MG groups. A previous study concerning the endothelium [43] suggested that the effect of trans-fat as an atherogenic factor is not entirely mediated by HDL-C. Table 4 shows a negative correlation between TFAs in the diets and plasma HDL-C content that did not reach significance (r D ¡0.920; p > 0.05). It has been suggested that compared to linoleic and palmitic acids, the HDL particles secreted in the presence of unsaturated trans-FAs may be less efficient in promoting cholesterol efflux from the cells. Table 4 shows a significant positive correlation between TFAs in the diet and circulating LDL-C (r D 0.987; p < 0.05). Experimental studies have also shown that increased levels of LDL-C play a role in the development and progression of atherosclerosis [44,45]. The LDL-C/HDL-C ratio is a better predictor of the risk of heart disease than LDL-C alone [46,47]. It is therefore important to observe not only HDL-C or LDL-C alone but also their ratio. We evaluated ratios of proatherogenic to antiatherogenic lipoprotein measurements as LDL-C to HDL-C. The LDL-C/HDL-C ratios were higher in cells incubated with TFAs than in cells incubated with cis and saturated FA [46,48]. The LDL-C/HDL-C ratio reflects the 2-way traffic of cholesterol entering and leaving the arterial intima [47]. Fats were incorporated into heart cell membranes and thus could alter cellular and macromolecular components acting at the interface of the blood vessel wall. This could result in vascular lesions. The earliest lesions (fatty streaks), which contain inflammatory cells loaded with cholesterol, were observed in groups fed the SO diet. In fact, previous studies proved that dietary TFAs are atherogenic on their own, showing that consuming TFA from a manufactured elaidic acid–rich
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hydrogenated vegetable shortening stimulates atherosclerotic development [4]. The high concentration of LDL and the LDLC/HDL-C ratio seems to be a major reason for the entry of inflammatory cells. The LDL brings the cholesterol produced by the liver to the heart, which deposits on artery walls and thickens as the result of a buildup of fatty materials, and then gradually forms real fatty plaques, called atheromas. The degree of lumen reduction is more accentuated in a TFA-rich diet. Because CVD involves cardiac arteries and veins, a comparison between OSO and MG coronary veins was undertaken, revealing a much more important effect in the MG-rich diet than the OSO diet. For the MG group, the smooth muscle cells of the media adjacent to the intima were disarranged. Generally, the vein histology was less affected than the arteries. The media and adjacent adventitia may contain accumulations of lymphocytes, macrophages, and macrophage foam cells [49]. Therefore, TFAs induce atherosclerotic development in a dosedependent manner (MG > OSO > SO). Our results prove that TFAs have the capacity to directly stimulate atherosclerotic development on their own and not limited to indirect ways. In conclusion, we demonstrated that trans-fat intake changes the plasma lipoprotein composition depending on the TFA level in the supplemented fat. Tracking FA profiles in rats’ hearts showed changes in the FA distribution for all experimental groups. Consumption of TFAs, which were produced by partial hydrogenation of vegetable oils and by excessive heating of soybean oil at frying temperature, has been associated with a relative increase in endogenous TFAs in heart. An increased content of process-induced TFAs in the diet was associated with increased plasma lipid profile and histological aspects of coronary atherosclerotic lesions. Furthermore, the more the TFAs were incorporated in rats’ hearts, the more pronounced the coronary artery lesions were. Associations of increased intakes levels of process-induced TFAs with CHD risk are well established.
ACKNOWLEDGMENT We are grateful to the anonymous reviewers for their valuable comments and remarks.
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FUNDING The present research was supported by a grant from the Ministere de l’EnseignementSuperieur et de la Recherche Scientifique UR03ES08 “Nutrition-Functional Foods and Vascular Health” from the University of Monastir.
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Received June 2, 2014; accepted June 18, 2014.
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Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats' Heart and Dyslipidemia a
a
a
b
Madiha Dhibi PhD , Amira Mnari PhD , Faten Brahmi PhD , Zohra Houas Pr , Issam Chargui b
a
PhD , Wafa Kharroubi PhD & Mohamed Hammami Pr
a
a
Laboratory of Nutrition-Functional Foods and Vascular Health, Faculty of Medicine, University of Monastir, Monastir, TUNISIA b
Laboratory of Histology Cytology and Genetics, Faculty of Medicine, University of Monastir, Monastir, TUNISIA Published online: 20 Mar 2015.
Click for updates To cite this article: Madiha Dhibi PhD, Amira Mnari PhD, Faten Brahmi PhD, Zohra Houas Pr, Issam Chargui PhD, Wafa Kharroubi PhD & Mohamed Hammami Pr (2015): Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats' Heart and Dyslipidemia, Journal of the American College of Nutrition, DOI: 10.1080/07315724.2014.938183 To link to this article: http://dx.doi.org/10.1080/07315724.2014.938183
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Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats’ Heart and Dyslipidemia
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Madiha Dhibi, PhD, Amira Mnari, PhD, Faten Brahmi, PhD, Zohra Houas, Pr, Issam Chargui, PhD, Wafa Kharroubi, PhD, Mohamed Hammami, Pr Laboratory of Nutrition-Functional Foods and Vascular Health (M.D., A.M., F.B., W.K., M.H.), Laboratory of Histology Cytology and Genetics (Z.H., I.C.), Faculty of Medicine, University of Monastir, Monastir, TUNISIA Key words: trans-fatty acids, high-fat diet, cardiovascular disease, rats Objectives: A direct effect of process-induced trans-fatty acids (TFAs) on nonalcoholic fatty liver disease (NAFLD) as a cardiovascular disease (CVD) risk factor has previously been shown. We hypothesized that TFAs directly induced CVD. This article describes an investigation of the association between TFAs, provided by the consumption of oxidized soybean oil and margarine, and plasma lipid profiles, coronary artery lesions, and coronary fatty acids distribution in rats. Male rats were fed a standard chow or high-fat diet containing different TFA levels ranging from SO.
DISCUSSION The different types of diet were designed to be isoenergetic; therefore, each variation is due to the type of fat used. Daily
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feed intake and body weight gain throughout the experiment did not differ among experimental groups. Differences in the dietary FA composition induce differences in their deposition into the rats’ hearts. The relative levels of the total SFAs were not altered by high-fat diet. Our study showed that in rats, the food intake of PUFAs increase the level of this endogenous fraction in the heart, reflecting the accurate incorporation of these FAs depending to level importance in each diet as follows: SO > OSO > MG (Table 3). Fatty acids play an essential role in cellular metabolism as powerful modulators of cell membrane receptors and affect signal transduction, gene transcription, and eicosanoid metabolism [10] and in the physiological responses of cells by regulating membrane fluidity [11]. In fact, the role of FA oxidation is controversial. On one hand, FA oxidation is viewed as a protective mechanism for the disposal of potentially toxic free FAs but, on the other hand, increased oxidation of FAs can generate reactive oxygen species, which cause tissue damage [12]. Elevated levels of FAs are known to cause the production of reactive oxygen species and oxidative stress [13,14]. Lipid oxidation reactions proceed through the same basic mechanisms of lipid hydroperoxide formation and decomposition in biological systems and in foods [15]. Single hydroperoxide isomers are not stable but are readily isomerized to an equilibrium mixture of geometrical and positional hydroperoxide isomers [16,17]. In our previous study, we demonstrated that dietary trans-fat increases liver lipid peroxidation [5]. Fat oxidation might be influenced by the degree of unsaturation of FAs, in the order linolenic > linoleic > oleic [18]. Linoleic acid as omega-6 FA has been traditionally considered heart healthy [19]. However, in recent years, questions have been raised as to whether the consumption of linoleic acid has become excessive [20], to the point of actually contributing to an increased risk for coronary heart disease (CHD) via its conversion to arachidonic acid, the predominant substrate for proinflammatory prostaglandins, leukotrienes, thromboxane, and prostacyclin [21]. Dlouhy et al. [22] demonstrated that higher linoleic acid intakes tend to decrease serum LDL-C levels, which cannot be explained by our results because the MG diet with lower linoleic acid content reveale a significant increase in LDL-C. It is assumed that industrial trans-fats increase LDL-C, which is confirmed in this study by the MG diet, which significantly increased LDLC. Our findings clearly show that rats with hyperlipidemia induced by a high-fat feed exhibit trans-FA accumulation in their hearts. A positive correlation between total TFAs in diet and relative trans-isomers in the hearts of rats receiving these diets was observed (r D 0.965; p < 0.05). Hence, after feeding high-fat diets containing different levels of trans-fats for 4 weeks, the rats showed differently deposited trans-isomers in their hearts. Elaidic acid, which has been previously shown to be incorporated in many tissues [23], is known to accumulate in atherosclerotic lesions and is associated with increased risk of CHD [24,25] and was markedly increased in the hearts
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Fig. 2. Histological aspects of coronary arteries sections from control rats and rats fed high-fat diets. Normal artery histological aspect from a control: (A) and (B): H&E 32£ and 100£, respectively. Arteries from SO group: (C) and (D): H&E 32£ and 100£, respectively. Arteries from MG group: (E), (F), and (G): H&E 32£ and 100£, respectively. Black triangle indicates wall thickness. White triangle indicates lumen reduction. Black arrows show fat deposit. White arrows show media calcification.
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Trans-Fatty Acids and Dyslipidemia
Fig. 3. Histological aspects of coronary veins sections from control rats and rats fed a high-fat diet (H&E 32£). (a) Normal vein histological aspect from a control: (b) vein from SO group; (c) vein from OSO group; and (d) vein from MG group. Black triangle indicates wall thickness. White triangle indicates lumen reduction. Thin arrows show fat deposit.
of MG-fed rats compared to other groups. It has been previously reported that monounsaturated TFA isomers with 18-carbon chain length (trans-18:1), which comprise about 85% of the total TFA in foods [26], are some of the predominant TFAs present in the human diet [27,28]. A previous report was published showing that intake of trans-18:1 raised the LDL/HDLC level ratio in comparison with cis-18:1 [29]. Unlike transisomers of MUFA, trans-PUFA, essentially as trans-18:2 isomers, was detected in rats’ hearts in all experimental groups with relatively high levels in the MG group, although the predominant trans-isomer in the MG diet was the elaidic acid. trans-PUFA could be formed in vivo by desaturation of trans18:1 present in the diet. Supplementing the diet with oxidized oil resulted in relatively higher levels of heart trans-18:3 n3 in the OSO group than in the controls, and in SO and MG groups corresponding to their intake from the diet. Grandgirard et al. [28] have suggested that the pathways used to synthesize the trans long-chain n-3 PUFA are similar to those of the corresponding cis compounds but that the rate of conversion could be different. Trans-PUFA have been reported to have adverse effects on the plasma lipid profile compared to their cis-isomers [31]. Anderson et al. [30] and Beyers et al. [31] had shown that the position of the trans double bond in the 18:2 acid appears to influence its metabolic fate and incorporation into tissue lipids. Trans-18:2 isomers have been found to be more adversely related to CHD risk than are trans-18:1 [34– 36]. A possible explanation for these adverse effects on CVD
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is that trans-18:2 isomers are incorporated in the sn-2 position of phospholipids, where PUFAs are usually found [37]. This substitution might affect membrane properties and have effects on atherosclerotic pathways through increased macrophage adhesion [37,38]. In the present study, consumption of the 3 types of high-fat diets stimulated changes in plasma lipid markers. Plasma TG concentrations were significantly greater in the trans-fed rats than in the control rats. Trans-fats increase levels of TG compared to the intake of other fats [22,39]. Increased dietary intake of TFAs has been associated with deleterious effect on plasma TGs. Khan-Merchant et al. [41] suggested that animals fed a nonatherogenic diet did not develop atherosclerosis even in the presence of oxidized FAs. In the present study, oxidized oil increases TG and TC, which can be attributed to the TFA content in the oxidized oil compared to the fresh oil. This assumption was supported by the significant positive correlation between TFAs in the diet and circulating TG (r D 0.986; p < 0.05; Table 4). Rats fed a high-fat diet had hypercholesterolemia that differs depending to trans-isomers level, showing a close correlation with TFA levels in their diets (r D 0.978; p < 0.05). Although these effects would be expected to increase the risk of CVD, the relation between the intake of trans-fats and the incidence of CVD reported in prospective studies has been greater than that predicted by changes in circulating lipid levels alone [41]. It has been suggested that the process of atherosclerosis, which is fundamental to the occurrence of cardiovascular disease, is recognized as a
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Trans-Fatty Acids and Dyslipidemia Table 4. Pearson’s Correlations Assessed between TFA Levels in Diet and in Heart and Plasma Lipid Markers of Experimental Rats
TFAdiet TFAheart TC TG HDL LDL LDL/HDL ratio
TFAdiet
TFAheart
TC
TG
HDL
LDL
LDL/HDL Ratio
1 0.956* 0.978* 0.986* ¡0.920 0.987* 0.987*
1 0.979* 0.916 ¡0.885 0.966* 0.970*
1 0.971* ¡0.958* 0.997** 0.998**
1 ¡0.962* 0.986* 0.984*
1 ¡0.964* ¡0.962
1 1.000***
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TFA D trans-fatty acids, TC D total cholesterol, TG D triglycerides, HDL D high-density lipoprotein, LDL D low-density lipoprotein. Data are presented as r values. * p < 0.05. **p < 0.01. ***p < 0.001.
consequence of the interplay of a plethora of genetic and environmental factors, but lipoproteins remain the foundation of its pathogenesis [2]. In this study, plasma lipoprotein profiles were significantly affected by high-fat diets. It is assumed that industrial trans-fats increase LDL-C in a similar manner as saturated fat but, unlike saturated fat, it also decreases HDL-C. The association between the intake of TFAs and CHD has often been attributed to the impact of TFAs on plasma biomarkers for CHD risk, specifically, increases in concentrations of TC and LDL-C along with decreases in HDL-C [42]. Hence, the decrease in HDL-C in groups fed diets rich in different TFAs seems to be significant in the OSO and MG groups. A previous study concerning the endothelium [43] suggested that the effect of trans-fat as an atherogenic factor is not entirely mediated by HDL-C. Table 4 shows a negative correlation between TFAs in the diets and plasma HDL-C content that did not reach significance (r D ¡0.920; p > 0.05). It has been suggested that compared to linoleic and palmitic acids, the HDL particles secreted in the presence of unsaturated trans-FAs may be less efficient in promoting cholesterol efflux from the cells. Table 4 shows a significant positive correlation between TFAs in the diet and circulating LDL-C (r D 0.987; p < 0.05). Experimental studies have also shown that increased levels of LDL-C play a role in the development and progression of atherosclerosis [44,45]. The LDL-C/HDL-C ratio is a better predictor of the risk of heart disease than LDL-C alone [46,47]. It is therefore important to observe not only HDL-C or LDL-C alone but also their ratio. We evaluated ratios of proatherogenic to antiatherogenic lipoprotein measurements as LDL-C to HDL-C. The LDL-C/HDL-C ratios were higher in cells incubated with TFAs than in cells incubated with cis and saturated FA [46,48]. The LDL-C/HDL-C ratio reflects the 2-way traffic of cholesterol entering and leaving the arterial intima [47]. Fats were incorporated into heart cell membranes and thus could alter cellular and macromolecular components acting at the interface of the blood vessel wall. This could result in vascular lesions. The earliest lesions (fatty streaks), which contain inflammatory cells loaded with cholesterol, were observed in groups fed the SO diet. In fact, previous studies proved that dietary TFAs are atherogenic on their own, showing that consuming TFA from a manufactured elaidic acid–rich
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hydrogenated vegetable shortening stimulates atherosclerotic development [4]. The high concentration of LDL and the LDLC/HDL-C ratio seems to be a major reason for the entry of inflammatory cells. The LDL brings the cholesterol produced by the liver to the heart, which deposits on artery walls and thickens as the result of a buildup of fatty materials, and then gradually forms real fatty plaques, called atheromas. The degree of lumen reduction is more accentuated in a TFA-rich diet. Because CVD involves cardiac arteries and veins, a comparison between OSO and MG coronary veins was undertaken, revealing a much more important effect in the MG-rich diet than the OSO diet. For the MG group, the smooth muscle cells of the media adjacent to the intima were disarranged. Generally, the vein histology was less affected than the arteries. The media and adjacent adventitia may contain accumulations of lymphocytes, macrophages, and macrophage foam cells [49]. Therefore, TFAs induce atherosclerotic development in a dosedependent manner (MG > OSO > SO). Our results prove that TFAs have the capacity to directly stimulate atherosclerotic development on their own and not limited to indirect ways. In conclusion, we demonstrated that trans-fat intake changes the plasma lipoprotein composition depending on the TFA level in the supplemented fat. Tracking FA profiles in rats’ hearts showed changes in the FA distribution for all experimental groups. Consumption of TFAs, which were produced by partial hydrogenation of vegetable oils and by excessive heating of soybean oil at frying temperature, has been associated with a relative increase in endogenous TFAs in heart. An increased content of process-induced TFAs in the diet was associated with increased plasma lipid profile and histological aspects of coronary atherosclerotic lesions. Furthermore, the more the TFAs were incorporated in rats’ hearts, the more pronounced the coronary artery lesions were. Associations of increased intakes levels of process-induced TFAs with CHD risk are well established.
ACKNOWLEDGMENT We are grateful to the anonymous reviewers for their valuable comments and remarks.
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FUNDING The present research was supported by a grant from the Ministere de l’EnseignementSuperieur et de la Recherche Scientifique UR03ES08 “Nutrition-Functional Foods and Vascular Health” from the University of Monastir.
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Received June 2, 2014; accepted June 18, 2014.
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