-
Biochemical and Biophysical Research... Oct 2018Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very...
Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler mice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in the reeler mouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.
Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Brain; Cell Adhesion Molecules, Neuronal; Docosahexaenoic Acids; Extracellular Matrix Proteins; Fatty Acids; Gene Expression Regulation, Developmental; Lipid Metabolism; Lipids; Mice, Inbred ICR; Mice, Neurologic Mutants; Nerve Tissue Proteins; Phospholipids; Reelin Protein; Serine Endopeptidases; Stearoyl-CoA Desaturase
PubMed: 30241938
DOI: 10.1016/j.bbrc.2018.09.089 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2019The effect of different lipid emulsions (LEs) within the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear. This study investigated the...
BACKGROUND
The effect of different lipid emulsions (LEs) within the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear. This study investigated the effect of changing adult HPN patients from a soybean oil based LE (Intralipid) to either a fish oil containing LE (providing n-3 fatty acids) (SMOFLipid) or an olive oil based LE (ClinOleic).
METHODS
Thirty two adults receiving long-term HPN with Intralipid as the LE were transferred to receive either SMOFLipid (n = 13) or ClinOleic (n = 19) for 60 days. Liver function markers, cholesterol, triglycerides, a full profile of fatty acids, and several cytokines were measured at study entry and after 60 days.
RESULTS
SMOFLipid did not affect liver function markers, blood lipids or plasma cytokines. ClinOleic lowered both gamma-glutamyltranspeptidase (P = 0.044) and interleukin-8 (P = 0.030) concentrations. Both LEs induced marked changes in the fatty acid profile of plasma. SMOFLipid resulted in significant decreases in the proportions of linoleic acid, several other n-6 fatty acids and the essential fatty acid (EFA) deficiency indicator mead acid and significant increases in the proportions of the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. ClinOleic resulted in significant decreases in the proportions of some saturated fatty acids, linoleic acid, several n-6 fatty acids, all n-3 fatty acids and mead acid and a significant increase in the proportion of oleic acid. The ratio of mead to arachidonic acid in plasma was not altered by either SMOFLipid or ClinOleic. No patient had a mead acid to arachidonic acid ratio of >0.2, the cut-off used to indicate EFA deficiency.
CONCLUSION
Both SMOFLipid and ClinOleic significantly alter the fatty acid profile of plasma in adult HPN patients previously using Intralipid. Neither LE induces EFA deficiency in these patients. SMOFLipid did not alter liver function markers or inflammation. In contrast, ClinOleic decreased some, though not all, markers of liver function and inflammation. SMOFLipid and ClinOleic may both be considered for use in adult HPN patients.
Topics: Adult; Cholesterol; Cytokines; Emulsions; Fat Emulsions, Intravenous; Fatty Acids; Female; Fish Oils; Humans; Liver; Liver Function Tests; Male; Olive Oil; Parenteral Nutrition, Home; Phospholipids; Plant Oils; Prospective Studies; Soybean Oil; Triglycerides
PubMed: 29907355
DOI: 10.1016/j.clnu.2018.05.028 -
Prostaglandins, Leukotrienes, and... Apr 2018Since the 1950's nutrition recommendations have focussed on the replacement of saturated fats in the diet with polyunsaturated fats, a strategy that continues to this... (Review)
Review
Since the 1950's nutrition recommendations have focussed on the replacement of saturated fats in the diet with polyunsaturated fats, a strategy that continues to this day. Despite supporting evidence from clinical trials for the advantages of Mediterranean diets, there has been less attention paid to the role of monounsaturated fats. It has been known for many years that diets high in linoleic acid (LA) compete for the incorporation of omega 3 fatty acids into tissues. What is also clear is that diets rich in LA are not free from concerns and the discovery of oxlams, oxygenated derivatives of LA, having potent inflammatory effects may help us question the dogma of LA rich diets. Given that dietary oleic acid a prime constituent of Mediterranean diets can be metabolised to Mead acid (ETrA) has in the past been a cause for concern, but new data showing the anti-inflammatory effects of ETrA suggest that there is a need for further research about the benefits of monounsaturated oils on human health. Finally, there is a need to re-examine how dietary fats are monitored in clinical studies. The current method of focussing on esterified fatty acids may be too insensitive to detect clinically important changes.
Topics: Biomedical Research; Clinical Trials as Topic; Diet; Diet, Mediterranean; Dietary Fats; Fatty Acids; Humans
PubMed: 29628045
DOI: 10.1016/j.plefa.2018.01.003 -
Characterization of Fatty Acid Profiles in Infants With Intestinal Failure-Associated Liver Disease.JPEN. Journal of Parenteral and Enteral... Jan 2018The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)-dependent infants with intestinal failure-associated liver disease...
BACKGROUND
The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)-dependent infants with intestinal failure-associated liver disease (IFALD) receiving soybean oil-based lipid emulsion (SO) doses of ∼3 and ∼1 g/kg/d.
METHODS
Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil-based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight- and length-for-age z scores were also reviewed.
RESULTS
Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO-S) (n = 14, range of dosage 2.06-3.31 g/kg/d) and reduced SO (SO-R) (n = 35, range of dosage 0.90-1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO-R had significantly higher Mead acid and lower α-linolenic, eicosapentaenoic, linoleic, stearic, total ω-3, and total ω-6 fatty acid levels than patients who received SO-S (P < .01). Triene:tetraene ratios were higher in patients who received SO-R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD).
CONCLUSION
PN-dependent infants with IFALD receiving SO-R have different FAPs than patients receiving SO-S. No patients in either group had biochemical EFAD.
Topics: Fat Emulsions, Intravenous; Fatty Acids; Female; Fish Oils; Humans; Infant; Intestinal Diseases; Liver Diseases; Male; Parenteral Nutrition; Prospective Studies; Retrospective Studies; Soybean Oil
PubMed: 29505154
DOI: 10.1002/jpen.1026 -
Prostaglandins, Leukotrienes, and... Jan 2018In mammals, FADS2 catalyzes "front-end" Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereas FADS1 has Δ5-desaturase activity. Eighteen and 20-carbon...
INTRODUCTION
In mammals, FADS2 catalyzes "front-end" Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereas FADS1 has Δ5-desaturase activity. Eighteen and 20-carbon precursors to highly unsaturated n-3 and n-6 fatty acids are the usual substrates for FADS1 and FADS2. Our main objective was to characterize the metabolic fate of oleic acid (OA) due to action of FADS gene products.
METHODS
MCF-7 cells were stably transformed with either FADS1 or FADS2 or empty vector. A series of dose-response experiments were conducted with albumin-bound fatty acid substrates (18:1n-9 and 20:1n-9) provided in concentrations up to 100µM. Cells were harvested after 24h, after which FAME were prepared and analyzed by GC-FID and covalent adduct chemical ionization tandem mass spectrometry (CACI-MS/MS).
RESULTS
When stably transformed cells were incubated with 18:1n-9, FADS1 and control cells elongated 18:1n-9 → 20:1n-9 (11-20:1), while FADS2 cells Δ6 desaturated, elongated, and then Δ5 desaturated via FADS1 coded activity leading to Mead acid, 9-18:1 → 6,9-18:2 → 8,11-20:2 (20:2n-9) → 6,8,11-20:3 (20:3n-9). Surprisingly, FADS1 cells Δ7 desaturated 11-20:1 → 7,11-20:2, the latter detected at low levels in control and FADS2 cells. Our results imply three pathways operate on 18:1n-9: 1) 18:1n-9 → 18:2n-9 → 20:2n-9 → 20:3n-9; 2) 18:1n-9 → 20:1n-9 → 20:2n-9 → 20:3n-9 and 3) 18:1n-9 → 20:1n-9 → 7,11-20:2.
CONCLUSION
Alternative pathways for oleic acid metabolism exist depending on FADS2 or FADS1 activities, we present the first evidence of Δ7 desaturation via the FADS1 gene product.
Topics: 8,11,14-Eicosatrienoic Acid; Delta-5 Fatty Acid Desaturase; Fatty Acid Desaturases; Fatty Acids; Fatty Acids, Omega-6; Humans; MCF-7 Cells; Oleic Acid
PubMed: 29413358
DOI: 10.1016/j.plefa.2017.11.004 -
Journal of Lipid Research Mar 2018The remodeling of PUFAs by the Lands cycle is responsible for the diversity of phospholipid molecular species found in cells. There have not been detailed studies of the...
The remodeling of PUFAs by the Lands cycle is responsible for the diversity of phospholipid molecular species found in cells. There have not been detailed studies of the alteration of phospholipid molecular species as a result of serum starvation or depletion of PUFAs that typically occurs during tissue culture. The time-dependent effect of cell culture on phospholipid molecular species in RAW 264.7 cells cultured for 24, 48, or 72 h was examined by lipidomic strategies. These cells were then stimulated to produce arachidonate metabolites derived from the cyclooxygenase pathway, thromboxane B, PGE, and PGD, and the 5-lipoxygenase pathway, leukotriene (LT)B, LTC, and 5-HETE, which decreased with increasing time in culture. However, the 5-lipoxygenase metabolites of a 20:3 fatty acid, LTB, all -LTB, LTC, and 5-hydroxyeicosatrienoic acid, time-dependently increased. Molecular species of arachidonate containing phospholipids were drastically remodeled during cell culture, with a new 20:3 acyl group being populated into phospholipids to replace increasingly scarce arachidonate. In addition, the amount of TNFα induced by lipopolysaccharide stimulation was significantly increased in the cells cultured for 72 h compared with 24 h, suggesting that the remodeling of PUFAs enhanced inflammatory response. These studies supported the rapid operation of the Lands cycle to maintain cell growth and viability by populating PUFA species; however, without sufficient n-6 fatty acids, 20:3 n-9 accumulated, resulting in altered lipid mediator biosynthesis and inflammatory response.
Topics: Animals; Cell Culture Techniques; Chromatography, High Pressure Liquid; Eicosanoids; Mice; Phospholipids; RAW 264.7 Cells; Tandem Mass Spectrometry; Tumor Necrosis Factor-alpha
PubMed: 29353239
DOI: 10.1194/jlr.M083030 -
Biochemical and Biophysical Research... Feb 2018Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid...
Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD). In this study, an obvious hepatic lipid accumulation was observed in EFAD mice treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of PC in EFAD mice was not observed because of the increased Mead acid in PC. These results supposed that Mead acid in PC is important as a component of VLDL. It is possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion during EFAD.
Topics: 8,11,14-Eicosatrienoic Acid; Animals; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Fatty Liver; Lipid Metabolism; Lipoproteins, VLDL; Liver; Male; Mice, Inbred C57BL; Oxidation-Reduction; Phosphatidylcholines
PubMed: 29353041
DOI: 10.1016/j.bbrc.2018.01.064 -
Journal of Pediatric Gastroenterology... Jan 2018The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term... (Observational Study)
Observational Study
OBJECTIVE
The aim of this study was to study the relationship between insulin-like growth factor-1 (IGF-1), serum phospholipid fatty acids, and growth in healthy full-term newborns during infancy.
METHODS
Prospective observational study of a population-based Swedish cohort comprising 126 healthy, term infants investigating cord blood and serum at 2 days and 4 months of age for IGF-1 and phospholipid fatty acid profile and breast milk for fatty acids at 2 days and 4 months, compared with anthropometric measurements (standard deviation scores).
RESULTS
At all time-points arachidonic acid (AA) was negatively associated with IGF-1. IGF-1 had positive associations with linoleic acid (LA) at 2 days and 4 months and mead acid (MA) showed positive associations in cord blood. Multiple regression analyses adjusted for maternal factors (body mass index, weight gain, smoking, education), sex, birth weight and feeding modality confirmed a negative association for the ratio AA/LA to IGF-1. MA in cord blood correlated to birth size. Changes in the ratios of n-6/n-3 and AA/docosahexaenoic acid from day 2 to 4 months together with infants' weight and feeding modality determined 55% of the variability of delta-IGF-1. Breast-fed infants at 4 months had lower IGF-1 correlating with lower LA and higher AA concentrations, which in girls correlated with lower weight gain from birth to 4 months of age.
CONCLUSIONS
Our data showed interaction of n-6 fatty acids with IGF-1 during the first 4 months of life, and an association between MA and birth size when adjusted for confounding factors. Further follow-up may indicate whether these correlations are associated with later body composition.
Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Biomarkers; Child Development; Female; Follow-Up Studies; Growth; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Linoleic Acid; Male; Prospective Studies
PubMed: 28753183
DOI: 10.1097/MPG.0000000000001691 -
Nutrition and Metabolic Insights 2017People with profound developmental disabilities have some of the most severe neurological impairments seen in society, have accelerated mortality due to huge medical...
BACKGROUND
People with profound developmental disabilities have some of the most severe neurological impairments seen in society, have accelerated mortality due to huge medical challenges, and yet are often excluded from scientific studies. They actually have at least 2 layers of conditions: (1) the original disability and (2) multiple under-recognized and underexplored metabolic and nutritional imbalances involving minerals (calcium, zinc, and selenium), amino acids (taurine, tryptophan), fatty acids (linoleic acid, docosahexaenoic acid, arachidonic acid, adrenic acid, Mead acid, plasmalogens), carnitine, hormones (insulinlike growth factor 1), measures of oxidative stress, and likely other substances and systems.
SUMMARY
This review provides the first list of metabolic and nutritional abnormalities commonly found in people with profound developmental disabilities and, based on the quality of life effects of similar abnormalities in neurotypical people, indicates the potential effects of these abnormalities in this population which often cannot communicate symptoms.
KEY MESSAGES
We propose that improved understanding and management of these disturbed mechanisms would enhance the quality of life of people with profound developmental disabilities. Such insights may also apply to people with other conditions associated with disability, including some diseases requiring stem cell implantation and living in microgravity.
PubMed: 35185339
DOI: 10.1177/1178638817716457 -
Terapevticheskii Arkhiv 2016to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether...
AIM
to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA).
SUBJECTS AND METHODS
Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA.
RESULTS
Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells.
CONCLUSION
The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.
Topics: Adult; Animals; Anomura; Cardiovascular Diseases; Drug Monitoring; Eicosanoids; Erythrocytes; Fatty Acids; Fatty Acids, Omega-3; Female; Gas Chromatography-Mass Spectrometry; Humans; Lipid Regulating Agents; Male; Metabolic Syndrome; Middle Aged; Tumor Necrosis Factor-alpha
PubMed: 27636924
DOI: 10.17116/terarkh201688830-34