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 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 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 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.

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.

scholarly journals Can dietary intervention produce long-term reductionin insulin resistance?

2000 ◽  
Vol 83 (S1) ◽  
pp. S169-S172 ◽  
Author(s):  
Jim I. Mann
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Dietary Fat ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Lifestyle Changes ◽  
Visceral Adiposity

Insulin sensitivity is potentially enhanced by a range of diet-related changes including reduction of visceral adiposity, a reduction in saturated fatty acids, and possibly a redistribution of the proportions of various unsaturated fatty acids. While there is evidence to suggest that lifestyle changes can reduce the risk of progression of impaired glucose tolerance to type 2 diabetes, there are no clinical trials which have conclusively demonstrated that any measure can reduce insulin resistance in the long term to an extent that can prevent the development of type 2 diabetes and other clinical complications. Evidence concerning the possibilities for reducing visceral adiposity and altering the nature of dietary fat are therefore considered. Attempts to achieve prolonged and substantial weight reduction in adults have not been encouraging, and it may be that preventing further weight gain is the most realistic target in this age group. In childhood the attempts have been more successful. The development of new approaches to achieving behavioural change and an environment which facilitates physical activity and appropriate food choices will be essential for more successful individual and population attempts to facilitate reduction in insulin resistance by weight loss. Changes in the nature of dietary fat appear to be more easily achieved. This is already a component of dietary advice aimed at cardiovascular risk reduction, and should be reinforced now with a view to also achieving a reduction in insulin resistance.

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.

EFFECT OF GINGER, LEMURU FISH OIL SAPONIFICATION AND OLIVE OIL ON COMPOSITION FATTY ACID OF BEEF

2014 ◽  
Vol 4 (1) ◽  
pp. 31-39
Author(s):  
Siwitri Kadarsih
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Olive Oil ◽  
Rice Bran ◽  
Dry Matter ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Omega 3 ◽  
Omega 6

The objective was to get beef that contain unsaturated fatty acids (especially omega 3 and 6), so as to improve intelligence, physical health for those who consume. The study design using CRD with 3 treatments, each treatment used 4 Bali cattle aged approximately 1.5 years. Observations were made 8 weeks. Pasta mixed with ginger provided konsentrat. P1 (control); P2 (6% saponification lemuru fish oil, olive oil 1%; rice bran: 37.30%; corn: 62.70%; KLK: 7%, ginger paste: 100 g); P3 (lemuru fish oil saponification 8%, 2% olive oil; rice bran; 37.30; corn: 62.70%; KLK: 7%, ginger paste: 200 g). Konsentrat given in the morning as much as 1% of the weight of the cattle based on dry matter, while the grass given a minimum of 10% of the weight of livestock observation variables include: fatty acid composition of meat. Data the analyzies qualitative. The results of the study showed that the composition of saturated fatty acids in meat decreased and an increase in unsaturated fatty acids, namely linoleic acid (omega 6) and linolenic acid (omega 3), and deikosapenta deikosaheksa acid.Keywords : 

Differential Effects of Dietary Fatty Acids on Body Composition and Adiposity

2020 ◽  
Vol 16 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Hadi Emamat ◽  
Zahra Yari ◽  
Hossein Farhadnejad ◽  
Parvin Mirmiran
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Total Body Weight ◽  
Fat Distribution ◽  
Monounsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Dietary Fats ◽  
Total Body

Recent evidence has highlighted that fat accumulation, particularly abdominal fat distribution, is strongly associated with metabolic disturbance. It is also well-recognized that the metabolic responses to variations in macronutrients intake can affect body composition. Previous studies suggest that the quality of dietary fats can be considered as the main determinant of body-fat deposition, fat distribution, and body composition without altering the total body weight; however, the effects of dietary fats on body composition have controversial results. There is substantial evidence to suggest that saturated fatty acids are more obesogen than unsaturated fatty acids, and with the exception of some isomers like conjugate linoleic acid, most dietary trans fatty acids are adiposity enhancers, but there is no consensus on it yet. On the other hand, there is little evidence to indicate that higher intake of the n-3 and the n-6 polyunsaturated fatty acids can be beneficial in attenuating adiposity, and the effect of monounsaturated fatty acids on body composition is contradictory. Accordingly, the content of this review summarizes the current body of knowledge on the potential effects of the different types of dietary fatty acids on body composition and adiposity. It also refers to the putative mechanisms underlying this association and reflects on the controversy of this topic.

scholarly journals Explore the gene network regulating the composition of fatty acids in cottonseed

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lihong Ma ◽  
Xinqi Cheng ◽  
Chuan Wang ◽  
Xinyu Zhang ◽  
Fei Xue ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Linolenic Acid ◽  
Gene Network ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Accumulation Pattern ◽  
Time Points ◽  
Expression Characteristics

Abstract Background Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. Results In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5–15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10–60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25–50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. Conclusions These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

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