scholarly journals Mechanisms of Action of trans Fatty Acids

2019 ◽  
Vol 11 (3) ◽  
pp. 697-708 ◽  
Author(s):  
Antwi-Boasiako Oteng ◽  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Er Stress ◽  
Trans Fatty Acids ◽  
Cholesterol Synthesis ◽  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Regulatory Element ◽  
Saturated Fatty Acids ◽  
Mechanisms Of Action ◽  
Plasma Lipoproteins

ABSTRACT Human studies have established a positive association between the intake of industrial trans fatty acids and the development of cardiovascular diseases, leading several countries to enact laws that restrict the presence of industrial trans fatty acids in food products. However, trans fatty acids cannot be completely eliminated from the human diet since they are also naturally present in meat and dairy products of ruminant animals. Moreover, bans on industrial trans fatty acids have not yet been instituted in all countries. The epidemiological evidence against trans fatty acids by far overshadows mechanistic insights that may explain how trans fatty acids achieve their damaging effects. This review focuses on the mechanisms that underlie the deleterious effects of trans fatty acids by juxtaposing effects of trans fatty acids against those of cis-unsaturated fatty acids and saturated fatty acids (SFAs). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids. Overall, in vivo and in vitro studies demonstrate that industrial trans fatty acids promote inflammation and endoplasmic reticulum (ER) stress, although to a lesser degree than SFAs, whereas cis-unsaturated fatty acids are protective against ER stress and inflammation. Additionally, industrial trans fatty acids promote fat storage in the liver at the expense of adipose tissue compared with cis-unsaturated fatty acids and SFAs. In cultured hepatocytes and adipocytes, industrial trans fatty acids, but not cis-unsaturated fatty acids or SFAs, stimulate the cholesterol synthesis pathway by activating sterol regulatory element binding protein (SREBP) 2–mediated gene regulation. Interestingly, although industrial and ruminant trans fatty acids show similar effects on human plasma lipoproteins, in preclinical models, only industrial trans fatty acids promote inflammation, ER stress, and cholesterol synthesis. Overall, clearer insight into the molecular mechanisms of action of trans fatty acids may create new therapeutic windows for the treatment of diseases characterized by disrupted lipid metabolism.

scholarly journals Saturated Fatty Acids Promote GDF15 Expression in Human Macrophages through the PERK/eIF2/CHOP Signaling Pathway

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3771
Author(s):  
Laurent L’homme ◽  
Benan Pelin Sermikli ◽  
Bart Staels ◽  
Jacques Piette ◽  
Sylvie Legrand-Poels ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Er Stress ◽  
Signaling Pathway ◽  
Promoter Region ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Growth Differentiation Factor 15 ◽  
Human Macrophages ◽  
Primary Monocyte

Growth differentiation factor-15 (GDF-15) and its receptor GFRAL are both involved in the development of obesity and insulin resistance. Plasmatic GDF-15 level increases with obesity and is positively associated with disease progression. Despite macrophages have been recently suggested as a key source of GDF-15 in obesity, little is known about the regulation of GDF-15 in these cells. In the present work, we sought for potential pathophysiological activators of GDF15 expression in human macrophages and identified saturated fatty acids (SFAs) as strong inducers of GDF15 expression and secretion. SFAs increase GDF15 expression through the induction of an ER stress and the activation of the PERK/eIF2/CHOP signaling pathway in both PMA-differentiated THP-1 cells and in primary monocyte-derived macrophages. The transcription factor CHOP directly binds to the GDF15 promoter region and regulates GDF15 expression. Unlike SFAs, unsaturated fatty acids do not promote GDF15 expression and rather inhibit both SFA-induced GDF15 expression and ER stress. These results suggest that free fatty acids may be involved in the control of GDF-15 and provide new molecular insights about how diet and lipid metabolism may regulate the development of obesity and T2D.

scholarly journals Differences Between Fat-Related Characteristics of Sour Cream and Sour Cream Analogues

2020 ◽  
Vol 49 (4) ◽  
pp. 390-397
Author(s):  
T. Izsó ◽  
Gy. Kasza ◽  
L. Somogyı
Keyword(s):  
Fatty Acids ◽  
Dairy Products ◽  
Trans Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Gap Filling ◽  
Nutritional Values ◽  
Common Practices ◽  
Fat Composition ◽  
Sour Cream

Modification of dairy products’ fat composition or replacement by other fats are common practices in the industry. Products in which milkfat is partially or wholly substituted by vegetable fats are defined as dairy analogues. This study delivers gap-filling information about sour cream analogues in nutritional aspects, focusing on the fat-related attributes. Analogue sour creams contained 29.6% less saturated fatty acids, 88.4% less cholesterol and 88.7% more mono- and poly-unsaturated fatty acids than the sour creams. Trans fatty acids were present in both products, which could not be linked to artificial hydrogenation in either case. Digestibility of the examined samples might be different, as sour creams had more short and medium chain fatty acids than the analogues. Overall, sour cream analogues, besides serving as an alternative to sour cream, have particular advantages based on their nutritional values.

scholarly journals Destabilization of β-cell FIT2 by saturated fatty acids contribute to ER stress and diabetes

2021 ◽  
Author(s):  
Xiaofeng Zheng ◽  
Qing Wei Calvin Ho ◽  
Minni Chua ◽  
Olga Stelmashenko ◽  
Sneha Muralidharan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Transmembrane Protein ◽  
Saturated Fatty Acids ◽  
Protective Role ◽  
Sequencing Analysis ◽  
Β Cell ◽  
Obesity And Diabetes ◽  
Ceramide Synthases

ABSTRACTWestern type diets are linked to obesity and diabetes partly because of their high saturated fatty acid (SFA) content. We found that SFAs, but not unsaturated fatty acids (USFAs), reduced the number of lipid droplets (LDs) within pancreatic β-cells. Mechanistically, SFAs but not USFAs disabled LD biogenesis by inducing palmitoylation and subsequent ERAD-C mediated degradation of LD formation protein, Fat storage-Inducing Transmembrane protein 2 (FIT2). Targeted ablation of FIT2 reduced β-cell LD numbers, lowered β-cell ATP levels, reduced Ca2+ signaling, downregulated β-cell transcription factors (RNA sequencing analysis), and exacerbated diet-induced diabetes in mice. Subsequent mass spectrometry studies revealed increased C16:0 ceramide accumulation in islets of mice lacking β-cell FIT2 under lipotoxic conditions. Inhibition of ceramide synthases ameliorated the enhanced ER stress. Overexpression of FIT2 increased number of intracellular LDs and rescued SFA-induced ER-stress and apoptosis thereby highlighting the protective role of FIT2 and LDs against β-cell lipotoxicity and diet-induced diabetes.

scholarly journals Docosahexaenoic and Eicosapentaenoic Acids Prevent Altered-Muc2 Secretion Induced by Palmitic Acid by Alleviating Endoplasmic Reticulum Stress in LS174T Goblet Cells

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2179
Author(s):  
Quentin Escoula ◽  
Sandrine Bellenger ◽  
Michel Narce ◽  
Jérôme Bellenger
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Palmitic Acid ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Goblet Cells ◽  
The Impact

Diets high in saturated fatty acids (FA) represent a risk factor for the development of obesity and associated metabolic disorders, partly through their impact on the epithelial cell barrier integrity. We hypothesized that unsaturated FA could alleviate saturated FA-induced endoplasmic reticulum (ER) stress occurring in intestinal secretory goblet cells, and consequently the reduced synthesis and secretion of mucins that form the protective mucus barrier. To investigate this hypothesis, we treated well-differentiated human colonic LS174T goblet cells with palmitic acid (PAL)—the most commonly used inducer of lipotoxicity in in vitro systems—or n-9, n-6, or n-3 unsaturated fatty acids alone or in co-treatment with PAL, and measured the impact of such treatments on ER stress and Muc2 production. Our results showed that only eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids protect goblet cells against ER stress-mediated altered Muc2 secretion induced by PAL, whereas neither linolenic acid nor n-9 and n-6 FA are able to provide such protection. We conclude that EPA and DHA could represent potential therapeutic nutrients against the detrimental lipotoxicity of saturated fatty acids, associated with type 2 diabetes and obesity or inflammatory bowel disease. These in vitro data remain to be explored in vivo in a context of dietary obesity.

scholarly journals Modulation of Fatty Acid-Related Genes in the Response of H9c2 Cardiac Cells to Palmitate and n-3 Polyunsaturated Fatty Acids

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 537
Author(s):  
Silvia Cetrullo ◽  
Stefania D’Adamo ◽  
Veronica Panichi ◽  
Rosa Maria Borzì ◽  
Carla Pignatti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Molecular Mechanisms ◽  
Dietary Habits ◽  
Regulatory Element ◽  
Saturated Fatty Acids ◽  
Cardiac Cells ◽  
High Dose ◽  
Mrna Levels

While high levels of saturated fatty acids are associated with impairment of cardiovascular functions, n-3 polyunsaturated fatty acids (PUFAs) have been shown to exert protective effects. However the molecular mechanisms underlying this evidence are not completely understood. In the present study we have used rat H9c2 ventricular cardiomyoblasts as a cellular model of lipotoxicity to highlight the effects of palmitate, a saturated fatty acid, on genetic and epigenetic modulation of fatty acid metabolism and fate, and the ability of PUFAs, eicosapentaenoic acid, and docosahexaenoic acid, to contrast the actions that may contribute to cardiac dysfunction and remodeling. Treatment with a high dose of palmitate provoked mitochondrial depolarization, apoptosis, and hypertrophy of cardiomyoblasts. Palmitate also enhanced the mRNA levels of sterol regulatory element-binding proteins (SREBPs), a family of master transcription factors for lipogenesis, and it favored the expression of genes encoding key enzymes that metabolically activate palmitate and commit it to biosynthetic pathways. Moreover, miR-33a, a highly conserved microRNA embedded in an intronic sequence of the SREBP2 gene, was co-expressed with the SREBP2 messenger, while its target carnitine palmitoyltransferase-1b was down-regulated. Manipulation of the levels of miR-33a and SREBPs allowed us to understand their involvement in cell death and hypertrophy. The simultaneous addition of PUFAs prevented the effects of palmitate and protected H9c2 cells. These results may have implications for the control of cardiac metabolism and dysfunction, particularly in relation to dietary habits and the quality of fatty acid intake.

Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells

2006 ◽  
Vol 291 (2) ◽  
pp. E275-E281 ◽  
Author(s):  
Yuren Wei ◽  
Dong Wang ◽  
Farran Topczewski ◽  
Michael J. Pagliassotti
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Liver Cells ◽  
Caspase Activity ◽  
Dna Laddering ◽  
Er Homeostasis

Accumulation of lipids in nonadipose tissues can lead to cell dysfunction and cell death, a phenomenon known as lipotoxicity. However, the signaling pathways and mechanisms linking lipid accumulation to cell death are poorly understood. The present study examined the hypothesis that saturated fatty acids disrupt endoplasmic reticulum (ER) homeostasis and promote apoptosis in liver cells via accumulation of ceramide. H4IIE liver cells were exposed to varying concentrations of saturated (palmitate or stearate) or unsaturated (oleate or linoleate) fatty acids. ER homeostasis was monitored using markers of the ER stress response pathway, including phosphorylation of IRE1α and eIF2α, splicing of XBP1 mRNA, and expression of molecular chaperone (e.g., GRP78) and proapoptotic (CCAAT/enhancer-binding protein homologous protein) genes. Apoptosis was monitored using caspase activity and DNA laddering. Palmitate and stearate induced ER stress, caspase activity, and DNA laddering. Inhibition of caspase activation prevented DNA laddering. Unsaturated fatty acids did not induce ER stress or apoptosis. Saturated fatty acids increased ceramide concentration; however, inhibition of de novo ceramide synthesis did not prevent saturated fatty acid-induced ER stress and apoptosis. Unsaturated fatty acids rescued palmitate-induced ER stress and apoptosis. These data demonstrate that saturated fatty acids disrupt ER homeostasis and induce apoptosis in liver cells via mechanisms that do not involve ceramide accumulation.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (1) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (8) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

scholarly journals Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at ER monitoring and regulating fatty acids

2021 ◽  
Author(s):  
Song-iee Han ◽  
Masanori Nakakuki ◽  
Yoshimi Nakagawa ◽  
Yunong Wang ◽  
Masaya Araki ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Regulatory Element ◽  
Saturated Fatty Acids ◽  
Regulatory System ◽  
Proteolytic Activation ◽  
Rhomboid Protease ◽  
Aaa Atpase ◽  
Cholesterol Levels ◽  
Sterol Regulatory Element

The ER-embedded transcription factors, sterol-regulatory element-binding proteins (SREBPs), master regulators of lipid biosynthesis, are transported to Golgi for proteolytic activation to tune cellular cholesterol levels and regulate lipogenesis. However, mechanisms by which the cell responds to the levels of saturated or unsaturated fatty acids remain underexplored. Here we show that RHBDL4/RHBDD1, a rhomboid family protease, directly cleaves SREBP-1c at ER. The p97/VCP, AAA-ATPase complex then acts as an auxiliary segregase to extract the remaining ER-embedded fragment of SREBP-1c. Importantly, the enzymatic activity of RHBDL4 is enhanced by saturated fatty acids (SFAs), but inhibited by polyunsaturated fatty acids (PUFAs). Genetic deletion of RHBDL4 in mice fed on a Western diet enriched in SFAs and cholesterol prevented SREBP-1c from inducing genes for lipogenesis, particularly for synthesis and incorporation of PUFAs, and secretion of lipoproteins. The RHBDL4-SREBP-1c pathway reveals a regulatory system for monitoring fatty acid composition and maintaining cellular lipid homeostasis.

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya
Keyword(s):  
Fatty Acids ◽  
Experimental Model ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Coconut Oil ◽  
The Body ◽  
Regulatory Function ◽  
Omega 3 ◽  
White Rats ◽  
Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

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