Dysfunctional lipid metabolism is a key component in the development of metabolic syndrome, a very frequent condition characterized by dyslipidemia, insulin resistance, abdominal obesity and ...hypertension, which are related to an elevated risk for type 2 diabetes mellitus. The prevalence of metabolic syndrome is strongly associated with the severity of obesity; its physiopathology is related to both genetics and food intake habits, especially the consumption of a high-caloric, high-fat and high-carbohydrate diet. With the progress of scientific knowledge in the field of nutrigenomics, it was possible to elucidate how the majority of dietary fatty acids influence plasma lipid metabolism and also the genes expression involved in lipolysis and lipogenesis within hepatocytes and adipocytes. The aim of this review is to examine the relevant mechanistic aspects of dietary fatty acids related to blood lipids, adipose tissue metabolism, hepatic fat storage and inflammatory process, all of them closely related to the genesis of metabolic syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Linoleic acid (LA) and alpha linolenic acid (ALA) belong to the
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3 (omega-3) series of polyunsaturated fatty acids (PUFA), respectively. They are defined “essential” fatty ...acids since they are not synthesized in the human body and are mostly obtained from the diet. Food sources of ALA and LA are most vegetable oils, cereals and walnuts. This review critically revises the most significant epidemiological and interventional studies on the cardioprotective activity of PUFAs, linking their biological functions to biochemistry and metabolism. In fact, a complex series of desaturation and elongation reactions acting in concert transform LA and ALA to their higher unsaturated derivatives: arachidonic acid (AA) from LA, eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) from ALA. EPA and DHA are abundantly present in fish and fish oil. AA and EPA are precursors of different classes of pro-inflammatory or anti-inflammatory eicosanoids, respectively, whose biological activities have been evoked to justify risks and benefits of PUFA consumption. The controversial origin and clinical role of the
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6/
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3 ratio as a potential risk factor in cardiovascular diseases is also examined. This review highlights the important cardioprotective effect of
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3 in the secondary prevention of sudden cardiac death due to arrhythmias, but suggests caution to recommend dietary supplementation of PUFAs to the general population, without considering, at the individual level, the intake of total energy and fats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fatty acids (PUFAs) are known to induce on hepatic de novo lipogenesis ...(DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fatty acids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 %
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) diets (HFDs) enriched in saturated fatty acids (SFAs) or unsaturated fatty acids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fatty acid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BACKGROUND/PURPOSE: Dietary fat content is a primary factor associated with the increase in global obesity rates. There is a delay in achieving fat balance following exposure to a high-fat (HF) diet ...(≥ 40 % of total energy from fat) and fat balance is closely linked to energy balance. Exercise has been shown to improve this rate of adaptation to a HF diet. Recently, however, the role of dietary fatty acid composition on energy and macronutrient balance has come into question. METHODS: We chose studies that compared monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA). We have reviewed studies that measured diet-induced thermogenesis (DIT), energy expenditure (EE), or fat oxidation (FOx) in response to a HF meal challenge, or long-term dietary intervention comparing these fatty acids. RESULTS: While single-meal studies show that SFA induce lower DIT and FOx compared to unsaturated fats, the effect of the degree of unsaturation (MUFA vs. PUFA) appears to yet be determined. Long-term dietary interventions also support the notion that unsaturated fats induce greater EE, DIT, and/or FOx versus SFA and that a high MUFA diet induces more weight loss compared to a high SFA diet. Sex and BMI status also affect the metabolic responses to different fatty acids; however, more research in these areas is warranted. CONCLUSION: SFA are likely more obesigenic than MUFA, and PUFA. The unsaturated fats appear to be more metabolically beneficial, specifically MUFA ≥ PUFA > SFA, as evidenced by the higher DIT and FOx following HF meals or diets.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their ...sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.
The aim of this study was to estimate changes in 27 individual ...plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes.
Plasma phospholipid fatty acids were profiled at 3 time-points (1993–1997, 1998–2000, 2004–2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n–3 polyunsaturated fatty acids (PUFAs), plant n–3 PUFA, n–6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs).
Adjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: −0.63%), even-chain SFAs (−0.05%), n–6 PUFAs (−0.25%), and TFAs (−7.84%). In contrast, concentrations increased for marine n–3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n–3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n–3 PUFAs.
Even-chain SFAs and TFAs declined and marine n–3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the ...n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA ...from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n–3 (ɷ-3) PUFA concentrations are unknown.
We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n–3 PUFA concentrations.
Postmenopausal women (ages 50–79 y) were assigned to HT or placebo in the Women’s Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65–79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n = 610). RBC n–3 and n–6 (ɷ-6) PUFAs were quantified.
Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n–3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n–6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged.
HT increased RBC concentrations of the terminal n–3 and n–6 PUFAs (DHA and DPA n–6). These findings are consistent with an estrogen-induced increase in DHA and DPA n–6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women’s Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background/Objectives: Reduced consumption of trans-fatty acids (TFA) is desirable to lower coronary heart disease (CHD) risk. In practice, partially hydrogenated vegetable oils (PHVO) that contain ...both TFAs and other fatty acids are the unit of replacement and could be replaced with diverse alternative fats and oils. We performed quantitative estimates of CHD effects if a person's PHVO consumption were to be replaced with alternative fats and oils based on (1) randomized dietary trials and (2) prospective observational studies. Subjects/Methods: We performed meta-analyses of (1) the effects of TFAs on blood lipids and lipoproteins in controlled dietary trials and (2) associations of habitual TFA consumption with CHD outcomes in prospective cohort studies. On the basis of these results and corresponding findings for saturated fatty acids (SFA), cis-monounsaturated fatty acids (MUFA) and cis-polyunsaturated fatty acids (PUFA), we calculated the effects on CHD risk for replacing 7.5% of energy from three different PHVO formulations (containing 20, 35 or 45% TFAs) with butter, lard, palm or vegetable oils. Results: In controlled trials, each 1% energy replacement of TFAs with SFAs, MUFAs or PUFAs, respectively, decreased the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio by 0.31, 0.54 and 0.67; the apolipoprotein (Apo)-B/ApoAI ratio by 0.007, 0.010 and 0.011; and lipoprotein (Lp)(a) by 3.76, 1.39 and 1.11 mg/l (P<0.05 for each). We also included possible effects on C-reactive protein (CRP) of TFAs vs other fats from one trial. On the basis of these risk factor changes in controlled trials, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: -2.7% (butter) to -9.9% (canola)); 35% TFA PHVO (-11.9% (butter) to -16.0% (canola)); or 45% TFA PHVO (-17.6% (butter) to -19.8% (canola)). In prospective cohort studies, each 2% energy replacement of TFAs with SFAs, MUFAs or PUFAs would lower CHD risk by 17% (95% confidence interval (CI)=7-25%), 21% (95% CI=12-30%) or 24% (95% CI=15-33%), respectively. On the basis of these associations in observational studies, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: +0.5% (butter) to -21.8% (soybean)); 35% TFA PHVO (-14.4% (butter) to -33.4% (soybean)); or 45% TFA PHVO (-22.4% (butter) to -39.6% (soybean)). The demonstrated effects on TC/HDL-C, ApoB/ApoAI, Lp(a), and CRP in randomized feeding trials together accounted for approximately 65-80% and approximately 50% of the estimated risk reduction for replacing PHVO with animal fats and vegetable oils, respectively, that would be calculated from prospective cohort studies. Conclusions: Effects on CHD risk of removing PHVO from a person's diet vary depending on the TFA content of the PHVO and the fatty acid composition of the replacement fat or oil, with direct implications for reformulation of individual food products. Accounting for the summed effects of TFAs on multiple CHD risk factors provides more accurate estimates of potential risk reduction than considering each risk factor in isolation, and approaches the estimated risk reduction derived from prospective cohort studies.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Revealing the expression patterns of fatty acid and amino acid transporters as affected by dietary n-6:n-3 PUFA ratio would be useful for further clarifying the importance of the balance between n-6 ...and n-3 PUFA. A total of ninety-six finishing pigs were fed one of four diets with the ratio of 1:1, 2·5:1, 5:1 and 10:1. Pigs fed the dietary n-6:n-3 PUFA ratio of 5:1 had the highest (P< 0·05) daily weight gain, and those fed the dietary n-6:n-3 PUFA ratio of 1:1 had the largest loin muscle area (P< 0·01). The concentration of n-3 PUFA was raised as the ratio declined (P< 0·05) in the longissimus dorsi and subcutaneous adipose tissue. The contents of tryptophan, tasty amino acids and branched-chain amino acids in the longissimus dorsi were enhanced in pigs fed the dietary n-6:n-3 PUFA ratios of 1:1–5:1. The mRNA expression level of the fatty acid transporter fatty acid transport protein-1 (FATP-1) was declined (P< 0·05) in the longissimus dorsi of pigs fed the dietary n-6:n-3 PUFA ratios of 1:1–5:1, and increased (P< 0·05) in the subcutaneous adipose tissue of pigs fed the dietary n-6:n-3 PUFA ratios of 5:1 and 10:1. The expression profile of FATP-4 was similar to those of FATP-1 in the adipose tissue. The mRNA expression level of the amino acid transceptors LAT1 and SNAT2 was up-regulated (P< 0·05) in the longissimus dorsi of pigs fed the dietary n-6:n-3 PUFA ratios of 1:1 and 2·5:1. In conclusion, maintaining the dietary n-6:n-3 PUFA ratios of 1:1–5:1 would facilitate the absorption and utilisation of fatty acids and free amino acids, and result in improved muscle and adipose composition.
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