Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits

2004 ◽  
Vol 82 (1) ◽  
pp. 22-29 ◽  
Author(s):  
R Menéndez ◽  
R Más ◽  
J Pérez ◽  
R M González ◽  
S Jiménez
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cholesterol Concentration ◽  
Proximal Small Bowel ◽  
Long Chain

D-003 is a mixture of very long chain saturated fatty acids (VLCSFA) purified from sugar cane wax with cholesterol-lowering effects proven in animal models and healthy volunteers. D-003 inhibits cholesterol biosynthesis through the regulation of HMG-CoA reductase activity. Rabbits fed diets enriched with casein develop endogenous hypercholesterolemia (EH), making them a very useful model for determining the mechanism of action of drugs affecting lipids. We examined whether D-003 prevented EH. Rabbits were fed a casein diet for 4 weeks, administered simultaneously with D-003 (5, 50, and 100 mg·kg–1·day–1). As expected, nontreated rabbits became hipercholesterolemic; however, as early as 15 days following administration, the treated group (50 and 100 mg·kg–1·day–1) had significantly decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C). Triglycerides were not affected; however, at study completion, HDL-C levels significantly increased at all the doses assayed. D-003 inhibited de novo synthesis of cholesterol, since the incorporation of 3H2O into sterols in the liver and proximal small bowel was significantly depressed. Also, D-003 significantly raised the rate of removal of [125I]-LDL from serum and significantly elevated [125I]-LDL binding activity to liver homogenates. Taken together, these results show that the efficacy of D-003 in reducing casein-derived hypercholesteromeia could involve, at least partially, an inhibition of hepatic cholesterol bio synthesis, which may elicit a decreased cholesterol concentration in hepatocytes, preventing the loss of hepatic LDL receptors induced by casein administration. However, since casein-induced hypercholesterolemia is also a consequence of a stimulation of cholesterol absorption in the lumen and an increase of the output of cholesterol associated with LDL, the effect of D-003 on cholesterol absorption and LDL synthesis by the liver should be investigated.Key words: D-003, very long chain saturated fatty acids, casein-fed rabbits, LDL-C, cholesterol biosynthesis, LDL clearance, LDL receptor.

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, A mixture of very long chain saturated fatty acids

2001 ◽  
Vol 44 (4) ◽  
pp. 299-304 ◽  
Author(s):  
Roberto Menéndez ◽  
Rosa Más ◽  
Ana MarÍa Amor ◽  
Idania Rodeiros ◽  
Rosa MarÍa Gonzalez ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Cultured Fibroblasts ◽  
Long Chain

scholarly journals Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Erik Hulander ◽  
Linnea Bärebring ◽  
Anna Turesson Wadell ◽  
Inger Gjertsson ◽  
Philip C. Calder ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Dietary Guidelines ◽  
Cholesterol Concentration ◽  
Link Type ◽  
Apolipoprotein B100 ◽  
Anti Inflammatory ◽  
Cardiovascular Profile

Abstract Background The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA. Methods Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure. Results Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period. Conclusion Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA. Trial registration This trial is registered at ClinicalTrials.gov as NCT02941055.

scholarly journals Long-Chain Saturated Fatty Acids, Palmitic and Stearic Acids, Enhance the Repair of Photosystem II

2020 ◽  
Vol 21 (20) ◽  
pp. 7509
Author(s):  
Haruhiko Jimbo ◽  
Kensuke Takagi ◽  
Takashi Hirashima ◽  
Yoshitaka Nishiyama ◽  
Hajime Wada
Keyword(s):  
Fatty Acids ◽  
Photosystem Ii ◽  
Chemical Potential ◽  
De Novo ◽  
Genetic Manipulation ◽  
Saturated Fatty Acids ◽  
De Novo Synthesis ◽  
Strong Light ◽  
Long Chain ◽  
Synechocystis Sp

Free fatty acids (FFA) generated in cyanobacterial cells can be utilized for the biodiesel that is required for our sustainable future. The combination of FFA and strong light induces severe photoinhibition of photosystem II (PSII), which suppresses the production of FFA in cyanobacterial cells. In the present study, we examined the effects of exogenously added FFA on the photoinhibition of PSII in Synechocystis sp. PCC 6803. The addition of lauric acid (12:0) to cells accelerated the photoinhibition of PSII by inhibiting the repair of PSII and the de novo synthesis of D1. α-Linolenic acid (18:3) affected both the repair of and photodamage to PSII. Surprisingly, palmitic (16:0) and stearic acids (18:0) enhanced the repair of PSII by accelerating the de novo synthesis of D1 with the mitigation of the photoinhibition of PSII. Our results show chemical potential of FFA in the regulation of PSII without genetic manipulation.

scholarly journals ISSFAL 2014 Debate: It Is Time to Update Saturated Fat Recommendations

2015 ◽  
Vol 66 (2-3) ◽  
pp. 104-108 ◽  
Author(s):  
Joyce A. Nettleton ◽  
Philippe Legrand ◽  
Ronald P. Mensink
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Saturated Fat ◽  
Density Lipoprotein ◽  
Monounsaturated Fatty Acids ◽  
Chd Risk ◽  
And Function

This paper summarizes a debate on whether to update recommendations for the consumption of saturated fatty acids (SFA); this debate was held at the 11th congress of the International Society for the Study of Fatty Acids and Lipids in Stockholm, Sweden, June 28-July 2, 2014. Recommendations to reduce SFA intakes are based largely on the premise that high intakes of SFA raise low-density lipoprotein (LDL)-cholesterol levels, which in turn increase the risk of coronary heart disease (CHD). Several systematic reviews question whether reducing SFA intakes lowers CHD risk. Arguing to revise SFA recommendations, Philippe Legrand noted that SFA are heterogeneous in structure and function, are synthesized de novo by humans and only certain SFA in excess have been linked to CHD risk. We cannot consider all SFA as a block. The effects of reducing SFA intakes depend on which nutrients replace them and on which biomarkers or endpoints are assessed, Ronald Mensink observed. The effects of reducing SFA on CHD risk vary with the nutrient of comparison, whether carbohydrates, monounsaturated or polyunsaturated fatty acids. Substitution of SFA with polyunsaturated fatty acids was associated with a lower incidence of cardiovascular disease, while the effects of substitution with monounsaturated fatty acids or high-glycemic index carbohydrates are less clear.

Differential effects of medium- and long-chain saturated fatty acids on blood lipid profile: a systematic review and meta-analysis

2018 ◽  
Vol 108 (4) ◽  
pp. 675-687 ◽  
Author(s):  
Nisha Panth ◽  
Kylie A Abbott ◽  
Cintia B Dias ◽  
Katie Wynne ◽  
Manohar L Garg
Keyword(s):  
Fatty Acids ◽  
Blood Lipids ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Weighted Mean ◽  
Lipids And Lipoproteins ◽  
Long Chain

Abstract Background Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL cholesterol analysis (I2 = 58%). Conclusion The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.

scholarly journals Gut metabolites influence susceptibility of neonatal mice to cryptosporidiosis

2020 ◽  
Author(s):  
Kelli L. VanDussen ◽  
Lisa J. Funkhouser-Jones ◽  
Marianna E. Akey ◽  
Deborah A. Schaefer ◽  
Kevin Ackman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Diarrheal Disease ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Intestinal Lumen ◽  
Apical Surface ◽  
Neonatal Mice ◽  
Long Chain

AbstractThe protozoan parasite Cryptosporidium is a leading cause of diarrheal disease in those with compromised or under-developed immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection, and then tested the isolated effects of these metabolites on C. parvum invasion and growth. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, while long-chain unsaturated fatty acids enhance C. parvum invasion. The influence of these two classes of metabolites on C. parvum infection likely reflects the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Hence, gut metabolites, either from diet or produced by the microbiota, play an important role in the early susceptibility to cryptosporidiosis seen in young animals.ImportanceCryptosporidium occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development, and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced growth of C. parvum in vitro and may increase susceptibility to infection in young mice. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids provide further insight into reliance on fatty acid salvage and metabolism of this enteric parasite.

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids

2000 ◽  
Vol 151 (1) ◽  
pp. 131 ◽  
Author(s):  
R. Menéndez ◽  
R. Más ◽  
D. Marrero ◽  
A.M. Amor ◽  
I. Rodeiro ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Cultured Fibroblasts ◽  
Long Chain

In vivo study of the biosynthesis of long-chain fatty acids using deuterated water

1995 ◽  
Vol 269 (2) ◽  
pp. E247-E252 ◽  
Author(s):  
H. O. Ajie ◽  
M. J. Connor ◽  
W. N. Lee ◽  
S. Bassilian ◽  
E. A. Bergner ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Chain Elongation ◽  
Deuterated Water ◽  
De Novo Synthesis ◽  
Isotopomer Distribution ◽  
Long Chain ◽  
Mass Isotopomer

To determine the contributions of preexisting fatty acid, de novo synthesis, and chain elongation in long-chain fatty acid (LCFA) synthesis, the synthesis of LCFAs, palmitate (16:0), stearate (18:0), arachidate (20:0), behenate (22:0), and lignocerate (24:0), in the epidermis, liver, and spinal cord was determined using deuterated water and mass isotopomer distribution analysis in hairless mice and Sprague-Dawley rats. Animals were given 4% deuterated water for 5 days or 8 wk in their drinking water. Blood was withdrawn at the end of these times for the determination of deuterium enrichment, and the animals were killed to isolate the various tissues for lipid extraction for the determination of the mass isotopomer distributions. The mass isotopomer distributions in LCFA were incompatible with synthesis from a single pool of primer. The synthesis of palmitate, stearate, arachidate, behenate, and lignocerate followed the expected biochemical pathways for the synthesis of LCFAs. On average, three deuterium atoms were incorporated for every addition of an acetyl unit. The isotopomer distribution resulting from chain elongation and de novo synthesis can be described by the linear combination of two binomial distributions. The proportions of preexisting, chain elongation, and de novo-synthesized fatty acids as a percentage of the total fatty acids were determined using multiple linear regression analysis. Fractional synthesis was found to vary, depending on the tissue type and the fatty acid, from 47 to 87%. A substantial fraction (24-40%) of the newly synthesized molecules was derived from chain elongation of unlabeled (recycled) palmitate.

scholarly journals NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 121
Author(s):  
Julie A. Schmidt ◽  
Georgina K. Fensom ◽  
Sabina Rinaldi ◽  
Augustin Scalbert ◽  
Marc J. Gunter ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Clinical Chemistry ◽  
Saturated Fatty Acids ◽  
Density Lipoprotein ◽  
Diet Group ◽  
Gas Liquid Chromatography ◽  
Very Low Density Lipoproteins ◽  
Animal Products ◽  
Total N ◽  
Metabolite Profiles

Metabolomics may help to elucidate mechanisms underlying diet-disease relationships and identify novel risk factors for disease. To inform the design and interpretation of such research, evidence on diet-metabolite associations and cross-assay comparisons is needed. We aimed to compare nuclear magnetic resonance (NMR) metabolite profiles between meat-eaters, fish-eaters, vegetarians and vegans, and to compare NMR measurements to those from mass spectrometry (MS), clinical chemistry and capillary gas-liquid chromatography (GC). We quantified 207 serum NMR metabolite measures in 286 male participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Using univariate and multivariate analyses, we found that metabolite profiles varied by diet group, especially for vegans; the main differences compared to meat-eaters were lower levels of docosahexaenoic acid, total n-3 and saturated fatty acids, cholesterol and triglycerides in very-low-density lipoproteins, various lipid factions in high-density lipoprotein, sphingomyelins, tyrosine and creatinine, and higher levels of linoleic acid, total n-6, polyunsaturated fatty acids and alanine. Levels in fish-eaters and vegetarians differed by metabolite measure. Concentrations of 13 metabolites measured using both NMR and MS, clinical chemistry or GC were mostly similar. In summary, vegans’ metabolite profiles were markedly different to those of men consuming animal products. The studied metabolomics platforms are complementary, with limited overlap between metabolite classes.

scholarly journals Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weng Sheng Kong ◽  
Naohiro Tsuyama ◽  
Hiroko Inoue ◽  
Yun Guo ◽  
Sho Mokuda ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Atopic Dermatitis ◽  
Breast Milk ◽  
Saturated Fatty Acids ◽  
Lymphoid Cells ◽  
Interleukin 17 ◽  
Immune System Development ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Long Chain

AbstractBreastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother’s milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.

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