Low intake of ruminant trans fatty acids ameliorates the disordered lipid metabolism in C57BL/6J mice fed a high-fat diet.

Currently, the health benefits of ruminant trans fatty acids (R-TFA) are still controversial. Our previous investigations indicated that R-TFA at higher dosages (1.3% and 4% E) caused disordered lipid metabolism in mice; however, through collecting R-TFA intake data in 9 provinces of China, it was suggested that, in 2021, the range of R-TFA intake for Chinese residents was about 0.053-0.307 g d-1. Based on the 2022 Nutritional Dietary Guidelines for Chinese Residents, the recommended daily energy supply from R-TFA was about 0.11%-0.15% E. However, the health effects of R-TFA at a lower dosage are still unknown; therefore, our current research aims to further explore the effects of R-TFA on health. Through in vivo experiments, it was shown that R-TFA (0.15% E) decreased body weight gain and serum cholesterol levels in C57BL/6J mice fed a high-fat diet, while it had no significant effect on mice fed a low-fat diet. Besides, hepatic histopathology analysis suggested that R-TFA (0.15% E) ameliorated the degree of hepatic steatosis and reduced intrahepatocyte lipid droplet accumulation in C57BL/6J mice fed a high-fat diet. Through lipidomics analysis, we further screened 8 potential lipid metabolites that participate in regulating the dysregulation of lipid metabolism. Finally, it was suggested that R-TFA (0.15% E) down-regulated the expression of genes related to inflammation and cholesterol synthesis while up-regulated the expression of genes related to cholesterol clearance, which might partially explain the salutary effect of R-TFA (0.15% E) in ameliorating the hepatic steatosis and improving disordered lipid metabolism in mice fed a high-fat diet. Our current research will provide a reference for the intake of R-TFA and, furthermore, give some insights into understanding the health effects of R-TFA.

Integration of hepatic lipidomics and transcriptomics reveals the effect of butter-derived ruminant trans fatty acids on lipid metabolism in C57BL/6J mice.

Dysregulation of lipid metabolism results in metabolism-related diseases. Our previous research indicated that 1.3% E and 4% E ruminant trans fatty acids (R-TFA) caused dyslipidemia and promoted atherosclerotic plaques in ApoE-/- mice, presenting detrimental effects. However, the effect of R-TFA on the lipid metabolism of normal mice remains unclear. Therefore, our current research aims to explore the effects of butter-derived R-TFAs on the lipid metabolism of C57BL/6J mice through the integration of lipidomics and transcriptomics. As a result, we found that 1.3% E butter-derived R-TFA promoted dyslipidemia and impaired hepatic function in C57BL/6J mice fed a high-fat diet, which was associated with an increase in DG (18:1/22:5), TG (18:1/18:2/22:4) and FA (24:5) as determined through lipidomics analysis, but had a less significant effect on C57BL/6J mice fed a low-fat diet. Through a combination analysis and verification of gene expression, we found that the arachidonic acid pathway might be involved in the disruption of lipid metabolism by butter-derived R-TFA. In addition, butter-derived R-TFA up-regulated the expression of unigene thromboxane-A synthase 1 (Tbxas1), arachidonate lipoxygenase 3 (Aloxe3), acyl-coenzyme A thioesterase 2 (Acot2), epoxide hydrolase 2 (Ephx2) and carbonyl reductase 3 (Cbr3) in C57BL/6J mice fed a high-fat diet. Herein, our research provides a new perspective for exploring the effects of butter-derived R-TFA on lipid metabolism and speculates on the possible mechanism of lipid metabolism disorder induced by butter-derived R-TFA in C57BL/6J mice fed a high-fat diet.

Elaidic acid induced NLRP3 inflammasome activation via ERS-MAPK signaling pathways in Kupffer cells.

Trans fatty acids (TFA) in food can cause liver inflammation. Activation of NOD-like receptor protein-3 (NLRP3) inflammasome is a key factor in the regulation of inflammation. Accumulating evidence suggests that ERS-induced NLRP3 inflammasome activation underlies the pathological basis of various inflammatory diseases, but the precise mechanism has not been fully elucidated. Therefore, this paper focused on TFA, represented by elaidic acid (EA), to investigate the mechanism of liver inflammation. Levels of mRNA and protein were detected by RT-qPCR and Western blotting, the release of proinflammatory cytokines was measured by ELISA, and intracellular Ca2+ levels were determined by flow cytometer using Fluo 4-AM fluorescent probes. Our research indicated that EA induced the endoplasmic reticulum stress (ERS) response in Kupffer cells (KCs), accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which resulted in NLRP3 inflammasome formation, and eventually increased the release of inflammatory factors. NLRP3 inflammasome activation was inhibited when KCs were pretreated with ERS inhibitors (4-PBA) and MAPK selective inhibitors. Furthermore, when ERS was blocked, the MAPK pathway was inhibited.

Differential Effects of Ruminant and Industrial 18-Carbon trans-Monounsaturated Fatty Acids (trans Vaccenic and Elaidic) on the Inflammatory Responses of an Endothelial Cell Line.

Endothelial dysfunction and inflammation are recognised factors in the development of atherosclerosis. Evidence suggests that intake of industrial trans fatty acids (TFAs) promotes endothelial dysfunction, while ruminant TFAs may have the opposite effect. The aim of this study was to compare the effects of elaidic acid (EA (18:1n-9t); an industrially produced TFA) and trans vaccenic acid (TVA (18:1n-7t); a natural TFA found in ruminant milk and meat) on inflammatory responses of endothelial cells (ECs). ECs (EA.hy926 cells) were cultured under standard conditions and exposed to TFAs (1 to 50 µM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments. TFAs were incorporated into ECs in a dose-dependent manner. Preincubation with EA (50 µM) increased production of MCP-1, RANTES, and IL-8 in response to TNF-α, while preincubation with TVA (1 µM) decreased production of ICAM-1 and RANTES in response to TNF-α. Preincubation with EA (50 µM) upregulated toll-like receptor 4 and cyclooxygenase 2 gene expression in response to TNF-α. In contrast, preincubation with TVA (1 µM) downregulated TNF-α induced nuclear factor kappa B subunit 1 gene expression. Preincubation of ECs with EA (50 µM) increased THP-1 monocyte adhesion. In contrast, preincubation of ECs with TVA (1 µM) reduced THP-1 monocyte adhesion, while preincubation of ECs with TVA (50 µM) decreased the level of surface expression of ICAM-1 seen following TNF-α stimulation. The results suggest that TVA has some anti-inflammatory properties, while EA enhances the response to an inflammatory stimulus. These findings suggest differential effects induced by the TFAs tested, fitting with the idea that industrial TFAs and ruminant TFAs can have different and perhaps opposing biological actions in an inflammatory context.

In vivo effects of olive oil and trans-fatty acids on miR-134, miR-132, miR-124-1, miR-9-3 and mTORC1 gene expression in a DMBA-treated mouse model.

Both the intake of beneficial olive oil and of harmful trans-fatty acids (TFAs) in consumed foods are of great significance in tumor biology. In our present study we examined the effects they exert on the expression patterns of miR-134, miR-132, miR-124-1, miR-9-3 and mTOR in the liver, spleen and kidney of mice treated with 7,12-dimethylbenz [a] anthracene (DMBA). Feeding of TFA-containing diet significantly increased the expression of all studied miRs and mTORC1 in all organs examined, except the expression of mTORC1 in the spleen and kidney. Diet containing olive oil significantly reduced the expression of miR-124-1, miR-9-3 and mTORC1 in the liver and spleen. In the kidney, apart from the mTORC1 gene, the expression of all miRs examined significantly decreased compared to the DMBA control. According to our results, the cell membrane protective, antioxidant, and anti-inflammatory effects of olive oil and the cell membrane damaging, inflammatory, and carcinogenic properties of TFA suggest negative feedback regulatory mechanisms. In contrast to our expectations, mTORC1 gene expression in the kidney has not been shown to be an appropriate biomarker-presumably, because the many complex effects that regulate mTOR expression may quench each other.

Evolution of Trans-fatty acid consumption in Thailand and strategies for its reduction.

Eliminating industrially produced trans-fatty acids (TFAs) from the food supply is one of the World Health Organization's (WHO's) priority targets to control and prevent non-communicable diseases. This review paper describes the strategies used to reduce TFA consumption in Thailand based on a situation analysis consisting of an assessment of TFA content in the national food supply, its intake, and stakeholder-based analysis of Strengths, Weaknesses, Opportunities, and Threats (SWOT). The analysis resulted in the drafting of a regulatory approach, which was then considered by stakeholders. Bakery products containing partially hydrogenated oils (PHOs) are the major sources of TFAs in Thailand. Palm and coconut oil as well as blending technology are locally available as PHO replacements. Thailand's Food and Drug Administration has taken legal action to prohibit the production, import, and distribution of PHOs and their products. Post-marketing TFA levels are currently being monitored, ie, TFAs in fat/oil and butter must not exceed 2% and 6% of fat content, respectively. For other food categories, TFAs must not exceed 0.5 g per serving unless the TFAs are from ruminant sources. The key factor to successfully reducing TFAs in Thailand is the partnership between public and private sectors, professional associations, and consumers, based on scientific evidence regarding the negative impact of TFA intake on cardiovascular health.

Cis-2 and trans-2-eisocenoic fatty acids are novel inhibitors for Mycobacterium tuberculosis Protein tyrosine phosphatase A.

Small protein tyrosine phosphatase (PtpA) of Mycobacterium tuberculosis is attributed to the development of latent tuberculosis infection, and hence bocomes an interesting target for drug development. In this communication, inhibition of PtpA by naturally occurring fatty acids cis-2 and trans-2-eicosenoic acid is investigated. Mtb PtpA was heterologously expressed in Escherichia coli, and the activity of PtpA was inhibited by cis-2 and trans-2 eicosenoic fatty acids. Both compunds showed strong inhibition of PtpA activity with IC50 at low micromolar concentration. As comparison, trans-11-eicosenoic acid only slightly inhibit PtpA. In silico analysis confirmed the inhibition of PtpB by cis-2-eicosenoic acid by formation of several hydrogen bonds. These findings show that cis-2 and trans-2 eicosenoic fatty acids are potential candidates for latent tuberculosis inhibitors.

Drinkable lecithin nanovesicles to study the biological effects of individual hydrophobic macronutrients and food preferences.

Fundamental nutritional studies on bioactive molecules require minimizing exposure to confounding foreign elements, like solvents. Herein, aqueous formulations of lecithin nanovesicles are proposed to study three individual trans fatty acids relevant to human nutrition: elaidic acid, trans-vaccenic acid and trans-palmitoleic acid. This proof-of-concept study describes the encapsulation of fatty acids, in vivo bioavailability, and the use of nanovesicles in behavioral experiments. The oral bioavailability of the encapsulated molecules and the selective exposure of animals to each trans-fatty acid of interest were confirmed in healthy rats. Behavioral studies also evidenced that nanovesicles can be used to evaluate the palatability of the lipids and investigate food preferences in mice. Altogether this study shows that lecithin nanovesicles offer an elegant tool to efficiently deliver hydrophobic molecules to animal models. This approach paves the way for future studies deconvoluting the nutritional effects of trans-fatty acids.

Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease.

SCOPE: The mechanisms underlying the deleterious effects of trans fatty acids on plasma cholesterol and non-alcoholic fatty liver disease (NAFLD) are unclear. Here, the aim is to investigate the molecular mechanisms of action of industrial trans fatty acids. METHODS AND RESULTS: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated, or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells shows that elaidate but not oleate or palmitate induces expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate is mediated by increased sterol regulatory element-binding protein 2 (SREBP2) activity and is dependent on SREBP cleavage-activating protein (SCAP), yet independent of liver-X receptor and ubiquitin regulatory X domain-containing protein 8. Elaidate decreases intracellular free cholesterol levels and represses the anticholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increases the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, alanine aminotransferase activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. CONCLUSION: Elaidate induces cholesterogenesis in vitro by activating the SCAP-SREBP2 axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.

Supplementation with trans fatty acid at 1% energy did not increase serum cholesterol irrespective of the obesity-related genotypes in healthy adult Japanese.

BACKGROUND AND OBJECTIVES: The excessive intake of trans fatty acids increases serum low-density lipoproteincholesterol and reduces high-density lipoprotein-cholesterol. We studied the effects of 1% energy trans fatty acid supplementation on serum lipid concentrations in healthy adult Japanese with different obesity-related gene polymorphisms. METHODS AND STUDY DESIGN: A randomized, double-blind, parallel trial was conducted in 53 healthy adults. The volunteers consumed one cookie containing either 1% energy or <0.01% energy (control) of trans fatty acids every day for 4 weeks, and a blood sample was then obtained after overnight fasting. The single nucleotide polymorphisms of the fat mass- and obesity-associated gene rs9939609 and beta-3 adrenergic receptor rs4994 were genotyped. RESULTS: The mean trans fatty acid intake of the control and trans fatty acid groups corresponded to 0.28% and 1.31 % energy, respectively. There were no significant differences in serum cholesterol (total, low-density lipoprotein and high-density lipoprotein) or triacylglycerol between the control and trans fatty acid groups. The responses of serum cholesterol, triacylglycerol, glucose, insulin and hemoglobinA1c were also independent of the fat mass- and obesity-associated gene and beta-3 adrenergic receptor gene variants. CONCLUSIONS: Our findings indicate that supplementation with 1% energy trans fatty acids has little effect on serum cholesterol in healthy adult Japanese, regardless of genotype of fat mass- and obesity-associated gene or beta-3 adrenergic receptor. More systematic studies, with respect to dietary trans fatty acid intakes above those used here, may be warranted to determine the tolerable upper level of dietary trans fatty acid.

Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids.

Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids.

Comparative Proteomics Analysis Reveals Trans Fatty Acid Isomers Activates Different Pathways in Human Umbilical Vein Endothelial Cell.

Trans fatty acid (TFA), a group of unsaturated fats with at least one double bond in the trans configuration, plays a role in lipid metabolism, the structure of the cell membrane phospholipids, and apoptosis. Previous studies demonstrated that TFA was associated with coronary heart disease, obesity, and insulin resistance. Herein, a quantitative proteomics approach estimated the relative abundance of proteins in human umbilical vein endothelial cells treated with TFA (two different TFA structural isomers: 9t-18:1 and 9t,12t-18:2). The results revealed that 174 identified proteins were significantly altered with respect to expression. Furthermore, based on the cutoff values, 35 proteins were differentially expressed in the 9t-18:1 group as compared to the control group, 69 proteins were differentially expressed in 9t,12t-18:2 group as compared to the control group, and 120 proteins were differentially expressed in the 9t,12t-18:2 group as compared to the 9t-18:1 group. Based on the bioinformatics analysis, we found that TFA could alter the structural constitution of the cytoskeleton through protein interactions, localization into the cell membrane, and incorporation into the phospholipid of the cell. In addition, 17 differential apoptosis-related proteins, including cell division cycle 42, superoxide dismutase 1, glyoxalase I, and macrophage migration inhibitory factor were also identified. Together, these results might emphasize the need for studying TFA-induced biological processes.

Effect of a trans fatty acid-enriched diet on mitochondrial, inflammatory, and oxidative stress parameters in the cortex and hippocampus of Wistar rats.

PURPOSE: Previously showed that dietary trans fatty acids (TFAs) may cause systemic inflammation and affect the central nervous system (CNS) in Wistar rats by increased levels of cytokines in the cerebrospinal fluid (CSF) and serum (Longhi et al. Eur J Nutr 56(3):1003-1016, 1). Here, we aimed to clarifying the impact of diets with different TFA concentrations on cerebral tissue, focusing on hippocampus and cortex and behavioral performance. METHODS: Wistar rats were fed either a normolipidic or a hyperlipidic diet for 90 days; diets had the same ingredients except for fat compositions, concentrations, and calories. We used lard in the cis fatty acid (CFA) group and PHSO in the TFA group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO), and (4) high partially hydrogenated soybean oil (HPHSO). Mitochondrial parameters, tumor necrosis factor alpha (TNF-α), 2'7'-dichlorofluorescein (DCFH) levels in brain tissue, and open field task were analyzed. RESULTS: A worse brain tissue response was associated with oxidative stress in cortex and hippocampus as well as impaired inflammatory and mitochondrial parameters at both PHSO concentrations and there were alterations in the behavioral performance. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. CONCLUSIONS: Partially hydrogenated soybean oil impaired cortical mitochondrial parameters and altered inflammatory and oxidative stress responses, and the hyperlipidic treatment caused locomotor and exploratory effects, but no differences on weight gain in all treatments. These findings suggest that quality is more important than the quantity of fat consumed in terms of CFA and TFA diets.

Influence of trans fatty acids on glucose metabolism in soleus muscle of rats fed diets enriched in or deprived of linoleic acid.

PURPOSE: Industrial trans fatty acid (TFA) intake leads to impaired glucose metabolism. However, the overall effects reported are inconsistent and vary with the dietary FA composition and TFA isomer type and levels. We investigated TFA effects on glucose uptake, incorporation and oxidation, and glycogen synthesis in incubated soleus muscle under basal conditions or after treatment with insulin and/or palmitate. METHODS: Male Wistar rats were fed either linoleic acid (LA)-enriched (+LA) or LA-deprived (-LA) diet, supplemented (+LA + TFA or -LA + TFA) or not with TFA, for 60 days. Soleus muscle glucose metabolism was assessed in the absence or presence of insulin and/or palmitic acid. RESULTS: Under basal conditions, TFA enhanced glucose uptake and oxidation regardless of the LA status. Both TFA-supplemented groups had lower insulin response to glucose metabolism. Under insulin-stimulated conditions, TFA prevented the palmitate inhibition of muscle glucose uptake and metabolism in the +LA + TFA group. CONCLUSION: Dietary TFA enhanced glucose utilization in incubated soleus muscle under basal conditions and prevented the palmitate-induced inhibition in insulin-stimulated conditions. However, TFA reduced the insulin response to glucose uptake and metabolism. The effects mentioned above were influenced by the FA profile modifications induced by the dietary LA levels, suggesting that lipid metabolization and incorporation into plasma membrane are important determining factors of glucose metabolism and insulin sensitivity.

Health effects of saturated and trans-fatty acid intake in children and adolescents: Systematic review and meta-analysis.

BACKGROUND: Elevated cholesterol has been linked to cardiovascular disease in adults and preclinical markers of atherosclerosis in children, thus reducing saturated (SFA) and trans-fatty acids (TFA) intake from an early age may help to reduce cholesterol and the risk of cardiovascular disease later in life. The aim of this review is to examine the evidence for health effects associated with reducing SFA and TFA intake in free-living children, adolescents and young adults between 2 to 19 years of age. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective cohort studies. Study selection, assessment, validity, data extraction, and analysis were undertaken as specified by the Cochrane Collaboration and the GRADE working group. Data were pooled using inverse variance models with random effects. DATA SOURCES: EMBASE; PubMed; Cochrane Central Register of Controlled Trials; LILACS; and WHO Clinical Trial Registry (up to July 2016). ELIGIBILITY CRITERIA FOR SELECTING TRIALS: RCTs involving dietary interventions aiming to reduce SFA or TFA intakes and a control group, and cohort studies reporting the effects of SFA or TFA exposures, on outcomes including blood lipids; measures of growth; blood pressure; insulin resistance; and potential adverse effects. Minimum duration was 13 days for RCTs and one year for cohort studies. Trials of weight loss or confounded by additional medical or lifestyle interventions were excluded. RESULTS: Compared with control diets, there was a highly statistically significant effect of reduced SFA intake on total cholesterol (mean difference (MD) -0.16 mmol/l, [95% confidence interval (CI): -0.25 to -0.07]), LDL cholesterol (MD -0.13 mmol/l [95% CI:-0.22 to -0.03]) and diastolic blood pressure (MD -1.45 mmol/l [95% CI:-2.34 to -0.56]). There were no significant effects on any other risk factors and no evidence of adverse effects. CONCLUSIONS: Advice to reduce saturated fatty acids intake of children results in a significant reduction in total and LDL-cholesterol levels as well as diastolic blood pressure without evidence of adverse effects on growth and development. Dietary guidelines for children and adolescents should continue to recommend diets low in saturated fat.

trans-Fatty acids promote proinflammatory signaling and cell death by stimulating the apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway.

Food-borne trans-fatty acids (TFAs) are mainly produced as byproducts during food manufacture. Recent epidemiological studies have revealed that TFA consumption is a major risk factor for various disorders, including atherosclerosis. However, the underlying mechanisms in this disease etiology are largely unknown. Here we have shown that TFAs potentiate activation of apoptosis signal-regulating kinase 1 (ASK1) induced by extracellular ATP, a damage-associated molecular pattern leaked from injured cells. Major food-associated TFAs such as elaidic acid (EA), linoelaidic acid, and trans-vaccenic acid, but not their corresponding cis isomers, dramatically enhanced extracellular ATP-induced apoptosis, accompanied by elevated activation of the ASK1-p38 pathway in a macrophage-like cell line, RAW264.7. Moreover, knocking out the ASK1-encoding gene abolished EA-mediated enhancement of apoptosis. We have reported previously that extracellular ATP induces apoptosis through the ASK1-p38 pathway activated by reactive oxygen species generated downstream of the P2X purinoceptor 7 (P2X7). However, here we show that EA did not increase ATP-induced reactive oxygen species generation but, rather, augmented the effects of calcium/calmodulin-dependent kinase II-dependent ASK1 activation. These results demonstrate that TFAs promote extracellular ATP-induced apoptosis by targeting ASK1 and indicate novel TFA-associated pathways leading to inflammatory signal transduction and cell death that underlie the pathogenesis and progression of TFA-induced atherosclerosis. Our study thus provides insight into the pathogenic mechanisms of and proposes potential therapeutic targets for these TFA-related disorders.

Nutrigenomic point of view on effects and mechanisms of action of ruminant trans fatty acids on insulin resistance and type 2 diabetes.

Evidence from observational studies suggests beneficial effects of ruminant trans fatty acids (rTFA) on insulin resistance (IR) and type 2 diabetes (T2D). However, beneficial effects of rTFA are not always observed in cell, animal, and human studies. This narrative review presents potential mechanisms of action of rTFA using nutrigenomics and microRNA results in an integrative model. In addition, the review presents factors, including measures of IR and T2D, dose and duration of studies, as well as health status, ethnicity, and genotypes of subjects, that may help explain the heterogeneity in response to rTFA supplementation. Future studies should consider these factors, as well as research in nutritional genomics, to better understand the effects of rTFA on IR and T2D.

Trans-Fatty Acid-Stimulated Mammary Gland Growth in Ovariectomized Mice is Fatty Acid Type and Isomer Specific.

We previously reported that the trans-18:2 fatty acid trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulates mammary gland development independent of estrogen and its receptor. Given the negative consequences of dietary trans-fatty acids on various aspects of human health, we sought to establish whether other trans-fatty acids could similarly induce ovary-independent mammary gland growth in mice. Prepubertal BALB/cJ mice were ovariectomized at 21 days of age then were fed diets enriched with cis-9, trans-11 CLA (c9,t11-CLA), or mixtures of trans-18:1 fatty acids supplied by partially hydrogenated sunflower, safflower, or linseed oil. The resultant mammary phenotype was evaluated 3 weeks later and compared to the growth response elicited by t10,c12-CLA, or the defined control diet. Whereas partially hydrogenated safflower oil increased mammary gland weight, none of the partially hydrogenated vegetable oils promoted mammary ductal growth. Similarly, the c9,t11-CLA supplemented diet was without effect on mammary development. Taken together, our data emphasize a unique effect of t10,c12-CLA in stimulating estrogen-independent mammary gland growth manifest as increased mammary ductal area and elongation that was not recapitulated by c9,t11-CLA or the partially hydrogenated vegetable oil diets.

Lipid Rafts Promote trans Fatty Acid-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

The effects of two fatty acids, oleic acid (OLA) and elaidic acid (ELA) on normal human umbilical vein endothelial cells (HUVEC) and non-rafts HUVEC were investigated in this study. The expression levels of inflammatory cytokines (ICAM-1, VCAM-1 and IL-6) were analyzed. Western blot was used to analyze the expression levels of inflammation-related proteins (NF-κB, ERK1/2) and toll-like receptors 4 (TLR4). The results showed that the levels of nuclear translocation of NF-κB p65 and phosphorylated ERK1/2 were significantly decreased only in non-lipid rafts cells pretreated with trans fatty acid (TFA). The expression of TLR4 in the ELA-treated normal cells was higher than that in non-lipid rafts HUVEC. When the lipid rafts was destroyed by methyl-ß-cyclodextrin, the levels of nuclear translocation of NF-κB p65, phosphorylated ERK1/2 and TLR4 were decreased significantly. Therefore, lipid rafts may be involved in TFA induced-inflammation in HUVEC through blocking the inflammatory signal pathway. Lipid rafts might be a platform for specific receptors such as TLR4 for TFA to activate the pro-inflammation on cell membranes.

Meta-regression analysis of the effect of trans fatty acids on low-density lipoprotein cholesterol.

We conducted a meta-regression of controlled clinical trial data to investigate quantitatively the relationship between dietary intake of industrial trans fatty acids (iTFA) and increased low-density lipoprotein cholesterol (LDL-C). Previous regression analyses included insufficient data to determine the nature of the dose response in the low-dose region and have nonetheless assumed a linear relationship between iTFA intake and LDL-C levels. This work contributes to the previous work by 1) including additional studies examining low-dose intake (identified using an evidence mapping procedure); 2) investigating a range of curve shapes, including both linear and nonlinear models; and 3) using Bayesian meta-regression to combine results across trials. We found that, contrary to previous assumptions, the linear model does not acceptably fit the data, while the nonlinear, S-shaped Hill model fits the data well. Based on a conservative estimate of the degree of intra-individual variability in LDL-C (0.1 mmoL/L), as an estimate of a change in LDL-C that is not adverse, a change in iTFA intake of 2.2% of energy intake (%en) (corresponding to a total iTFA intake of 2.2-2.9%en) does not cause adverse effects on LDL-C. The iTFA intake associated with this change in LDL-C is substantially higher than the average iTFA intake (0.5%en).