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

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

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.

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.

Abstract MP014: Very Long Chain Saturated Fatty Acids and Diabetes Risk: Meta-Analysis of Cohort Studies in the FORCE Consortium

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Amanda Fretts ◽  
Fumiaki Imamura ◽  
Chaoyu Yu ◽  
Alexis C Frazier-Wood ◽  
Maria Lankinen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Palmitic Acid ◽  
Lower Risk ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Arachidic Acid ◽  
Saturated Fatty Acids ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Long Chain

Background: Circulating saturated fatty acids are biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. Unlike palmitic acid (16:0), which has been extensively studied, little is known of the relationship of very long-chain saturated fatty acids (VLSFAs), with 20 carbons or more, to diabetes risk. Objective: To investigate the associations of circulating levels of VLSFA with incident diabetes. Methods: A meta-analysis was conducted within a consortium of prospective (cohort or nested case-control) studies having circulating measures of one or more VLSFAs, including arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0). Standardized analysis was conducted in each study using pre-specified models, exposures, outcomes, and covariates. Study-specific estimates were pooled using fixed effects meta-analysis. Results: Current findings were based on 9 participating studies, including 46,549 total participants and 13,750 incident diabetes. In multivariable-adjusted analyses, higher levels of all 3 VLSFAs were associated with lower risk of incident diabetes. Pooled RRs (95% CI) per interquintile range were 0.80 (0.71-0.90) for 20:0; 0.83 (0.76-0.91) for 22:0; and 0.70 (0.63-0.79) for 24:0, after adjustment for demographics, lifestyle factors and clinical conditions. Additional adjustments for circulating palmitic acid and triglyceride levels moved the RRs toward the null (illustrated for 24:0, in model 3 of the Figure ). Conclusions: Based on meta-analysis of results from several studies around the world, biomarker levels of VLSFA are associated with lower risk of incident diabetes, potentially mediated by effects on circulating triglycerides and 16:0.

scholarly journals Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Atp Production ◽  
Mitochondrial Fatty Acid ◽  
Mitochondrial Oxidation ◽  
Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

scholarly journals Recent Advances in the Pathophysiology of Fatty Acid Oxidation Defects: Secondary Alterations of Bioenergetics and Mitochondrial Calcium Homeostasis Caused by the Accumulating Fatty Acids

2020 ◽  
Vol 11 ◽  
Author(s):  
Alexandre Umpierrez Amaral ◽  
Moacir Wajner
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Calcium Homeostasis ◽  
Acid Oxidation ◽  
Cultured Fibroblasts ◽  
Medium Chain ◽  
Chain Acyl ◽  
Energy Deprivation ◽  
Long Chain

Deficiencies of medium-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein, isolated long-chain 3-hydroxyacyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase activities are considered the most frequent fatty acid oxidation defects (FAOD). They are biochemically characterized by the accumulation of medium-chain, long-chain hydroxyl, and long-chain fatty acids and derivatives, respectively, in tissues and biological fluids of the affected patients. Clinical manifestations commonly include hypoglycemia, cardiomyopathy, and recurrent rhabdomyolysis. Although the pathogenesis of these diseases is still poorly understood, energy deprivation secondary to blockage of fatty acid degradation seems to play an important role. However, recent evidence indicates that the predominant fatty acids accumulating in these disorders disrupt mitochondrial functions and are involved in their pathophysiology, possibly explaining the lactic acidosis, mitochondrial morphological alterations, and altered mitochondrial biochemical parameters found in tissues and cultured fibroblasts from some affected patients and also in animal models of these diseases. In this review, we will update the present knowledge on disturbances of mitochondrial bioenergetics, calcium homeostasis, uncoupling of oxidative phosphorylation, and mitochondrial permeability transition induction provoked by the major fatty acids accumulating in prevalent FAOD. It is emphasized that further in vivo studies carried out in tissues from affected patients and from animal genetic models of these disorders are necessary to confirm the present evidence mostly achieved from in vitro experiments.

scholarly journals Plasma Ceramides and Sphingomyelins in Relation to Atrial Fibrillation Risk: The Cardiovascular Health Study

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Paul N. Jensen ◽  
Amanda M. Fretts ◽  
Andrew N. Hoofnagle ◽  
Colleen M. Sitlani ◽  
Barbara McKnight ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Palmitic Acid ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Behenic Acid ◽  
Hazard Ratio ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.

scholarly journals Fast Diffusion of Very Long Chain Saturated Fatty Acids across a Bilayer Membrane and Their Rapid Extraction by Cyclodextrins

2009 ◽  
Vol 284 (48) ◽  
pp. 33296-33304 ◽  
Author(s):  
Biju K. Pillai ◽  
Ravi Jasuja ◽  
Jeffrey R. Simard ◽  
James A. Hamilton
Keyword(s):  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Bilayer Membrane ◽  
Fast Diffusion ◽  
Rapid Extraction ◽  
Long Chain

Very long chain saturated fatty acids in the diagnosis of adrenoleucodystrophy

Pathology ◽  
1983 ◽  
Vol 15 (1) ◽  
pp. 103
Author(s):  
A.J. Fellenberg ◽  
A.C. Pollard ◽  
A. Poulos ◽  
P. Sharp
Keyword(s):  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Long Chain

Conversion of octanoic acid into long-chain saturated fatty acids in premature infants fed a formula containing medium-chain triglycerides

Metabolism ◽  
1994 ◽  
Vol 43 (10) ◽  
pp. 1287-1292 ◽  
Author(s):  
V.P. Carnielli ◽  
E.J. Sulkers ◽  
C. Moretti ◽  
J.L.D. Wattimena ◽  
J.B. van Goudoever ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Premature Infants ◽  
Octanoic Acid ◽  
Saturated Fatty Acids ◽  
Medium Chain Triglycerides ◽  
Medium Chain ◽  
Long Chain
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