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The British Journal of Nutrition Aug 2006The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in...
The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in serum phospholipids from adult CF subjects with that of healthy subjects, and determine the role of the normal diet in this profile, we studied thirty-seven adult CF subjects with stable pulmonary disease and thirty-seven healthy controls matched for age, sex and nutritional status. A dietary questionnaire was obtained, anthropometric data were recorded, and the fatty acid profile measured by GLC. Compared with the controls, the percentages of myristic, palmitoleic and stearic acids and total MUFA were significantly higher in the CF group, and DHA, linoleic acid, total PUFA and n-6 fatty acids were significantly lower in the CF group. The CF subjects with worse pulmonary function and with pancreatic insufficiency had significantly lower levels of linoleic and n-6 fatty acids. The total energy intake was significantly higher in the CF subjects, although the energy distribution in the CF subjects and the controls was not different for the carbohydrates, lipids and proteins. No differences were detected in fat intake for MUFA (51 (SD 4) v. 52 (SD 4) %) or saturated fatty acids (33.5 (SD 5) v. 31.2 (SD 3.8) %), but the PUFA were slightly lower in the CF subjects (15.4 (SD 4.5) v. 17.4 (SD 4.2) %; P=0.02). The usual dietary intake of fatty acids by adult CF subjects does not appear to explain the difference in the fatty acid profile compared with controls. This suggests an abnormal fatty acid metabolism in CF subjects.
Topics: Adolescent; Adult; Cystic Fibrosis; Diet, Mediterranean; Dietary Fats; Energy Intake; Fatty Acids; Female; Humans; Lung; Male; Phospholipids; Prospective Studies
PubMed: 16923229
DOI: 10.1079/bjn20051655 -
Carcinogenesis Jul 2014It is well recognized that early detection and cancer prevention are significant armaments in the 'war against cancer'. Changes in lifestyle and diet have significant...
It is well recognized that early detection and cancer prevention are significant armaments in the 'war against cancer'. Changes in lifestyle and diet have significant impact on the global incidence of cancer. For over 30 years, many investigators have studied the concept of chemoprevention. More recently, with the demonstration that antiangiogenic activity reduces tumor growth, the concept of angioprevention has emerged as a novel strategy in the deterrence of cancer development (carcinogenesis). In this study, we utilized a fast growing, highly aggressive murine Lewis lung cancer model to examine the in vivo antitumor effects of a novel, dietary supplement, known as plant phospholipid/lipid conjugate (pPLC). Our goal was to determine if pPLC possessed direct antitumor activity with relatively little toxicity that could be developed as a chemoprevention therapy. We used pPLC directly in this in vivo model due to the lack of aqueous solubility of this novel formulation, which precludes in vitro experimentation. pPLC contains known antioxidants, ferulic acid and lipoic acid, as well as soy sterols, formulated in a unique aqueous-insoluble matrix. The pPLC dietary supplement was shown to suppress in vivo growth of this tumor model by 30%. We also demonstrated a significant decrease in tumor angiogenesis accompanied by increased apoptosis and present preliminary evidence of enhanced expression of the hypoxia-related genes pentraxin-3 and metallothionein-3, by 24.9-fold and 10.9-fold, respectively, compared with vehicle control. These findings lead us to propose using this plant phosolipid/lipid conjugate as a dietary supplement that may be useful in cancer prevention.
Topics: Animals; Apoptosis; Biomarkers, Tumor; Blotting, Western; Carcinoma, Lewis Lung; Cell Proliferation; Diet; Female; Gene Expression Profiling; Humans; Immunoenzyme Techniques; Lipids; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Phospholipids; Phytotherapy; Plant Preparations; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured
PubMed: 24510111
DOI: 10.1093/carcin/bgu039 -
International Journal of Molecular... Jan 2023Dietary composition substantially determines human health and affects complex diseases, including obesity, inflammation and cancer. Thus, food supplements have been...
Dietary composition substantially determines human health and affects complex diseases, including obesity, inflammation and cancer. Thus, food supplements have been widely used to accommodate dietary composition to the needs of individuals. Among the promising supplements are dietary phospholipids (PLs) that are commonly found as natural food ingredients and as emulsifier additives. The aim of the present study was to evaluate the effect of major PLs found as food supplements on the morphology of intestinal epithelial cells upon short-term and long-term high-dose feeding in mice. In the present report, the effect of short-term and long-term high dietary PL content was studied in terms of intestinal health and leaky gut syndrome in male mice. We used transmission electron microscopy to evaluate endothelial morphology at the ultrastructural level. We found mitochondrial damage and lipid droplet accumulation in the intracristal space, which rendered mitochondria more sensitive to respiratory uncoupling as shown by a mitochondrial respiration assessment in the intestinal crypts. However, this mitochondrial damage was insufficient to induce intestinal permeability. We propose that high-dose PL treatment impairs mitochondrial morphology and acts through extensive membrane utilization via the mitochondria. The data suggest that PL supplementation should be used with precaution in individuals with mitochondrial disorders.
Topics: Male; Humans; Mice; Animals; Phospholipids; Diet; Dietary Supplements; Mitochondria; Glycerophospholipids; Fatty Acids; Epithelial Cells
PubMed: 36675301
DOI: 10.3390/ijms24021788 -
JCI Insight Mar 2018Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although liver receptor homolog 1 (LRH-1) (encoded by NR5A2) is suppressed...
Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although liver receptor homolog 1 (LRH-1) (encoded by NR5A2) is suppressed in human NAFLD, evidence linking this phospholipid-bound nuclear receptor to hepatic lipid metabolism is lacking. Here, we report an essential role for LRH-1 in hepatic lipid storage and phospholipid composition based on an acute hepatic KO of LRH-1 in adult mice (LRH-1AAV8-Cre mice). Indeed, LRH-1-deficient hepatocytes exhibited large cytosolic lipid droplets and increased triglycerides (TGs). LRH-1-deficient mice fed high-fat diet displayed macrovesicular steatosis, liver injury, and glucose intolerance, all of which were reversed or improved by expressing wild-type human LRH-1. While hepatic lipid synthesis decreased and lipid export remained unchanged in mutants, elevated circulating free fatty acid helped explain the lipid imbalance in LRH-1AAV8-Cre mice. Lipidomic and genomic analyses revealed that loss of LRH-1 disrupts hepatic phospholipid composition, leading to lowered arachidonoyl (AA) phospholipids due to repression of Elovl5 and Fads2, two critical genes in AA biosynthesis. Our findings reveal a role for the phospholipid sensor LRH-1 in maintaining adequate pools of hepatic AA phospholipids, further supporting the idea that phospholipid diversity is an important contributor to healthy hepatic lipid storage.
Topics: Acetyltransferases; Age Factors; Animals; Arachidonic Acids; Diet, High-Fat; Disease Models, Animal; Fatty Acid Desaturases; Fatty Acid Elongases; Hepatocytes; Humans; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Phospholipids; Primary Cell Culture; Receptors, Cytoplasmic and Nuclear; Transgenes
PubMed: 29515023
DOI: 10.1172/jci.insight.96151 -
Journal of Biochemistry Aug 19761. The effect of dietary manipulation on the synthesis of triglycerides and phospholipids was investigated by determining the incorporation of labeled long-chain fatty...
1. The effect of dietary manipulation on the synthesis of triglycerides and phospholipids was investigated by determining the incorporation of labeled long-chain fatty acid or glycerol into these lipids in liver slices derived from normally fed, fasted, and fat-free refed rats. 2. Triglyceride synthesis was affected markedly by the dietary regime of the animal; the lowest rates were measured with fasted rats, and the highest ones with fat-free refed rats. 3. In contrast to triglyceride synthesis, phospholipid synthesis occured at virtually constant rates regardless of the dietary conditions. 4. Addition of large amounts of fatty acid to the incubation mixture resulted in a marked stimulation of triglyceride synthesis, whereas phospholipid synthesis was affected to a much smaller extent. 5. These results indicate that the synthesis of triglycerides and that of phospholipids are controlled independently, and that the availability of fatty acid in the cell contributes to the control of triglyceride synthesis.
Topics: Animals; Choline; Dietary Fats; Ethanolamines; Fasting; Glycerol; In Vitro Techniques; Linoleic Acids; Liver; Male; Palmitic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Rats; Triglycerides
PubMed: 1002667
DOI: 10.1093/oxfordjournals.jbchem.a131267 -
Journal of Neurochemistry Nov 2002The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic... (Comparative Study)
Comparative Study
Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats.
The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic acid (LNA) increases synaptic plasma membrane (SPM) cholesterol and phospholipid content, phospholipid 20:4n-6 and 22:6n-3 content, and Na,K-ATPase kinetics in rat pups at two and five weeks of age. At parturition, Sprague-Dawley rats were fed semi-purified diets containing either AA + docosahexaenoic acid (DHA), adequate LNA (control; 18:2n-6 : 18:3n-3 ratio of 7.1 : 1) or low LNA (18:2n-6 : 18:3n-39 ratio of 835 : 1). During the first two weeks of life, the rat pups received only their dams' milk. After weaning, pups received the same diet as their respective dams to five weeks of age. No significant difference was observed among rat pups fed the diet treatments for SPM cholesterol or total and individual phospholipid content at two and five weeks of age. Fatty acid analysis revealed that maternal dietary AA + DHA, compared with feeding the dams the control diet or the low LNA diet, increased 20:4n-6 in phosphatidylserine and 22:6n-3 content of SPM phospholipids. Rats fed dietary AA + DHA or the control diet exhibited a significantly increased Vmax for SPM Na,K-ATPase. Diet treatment did not alter the Km (affinity) of SPM Na,K-ATPase in rat pups at two and five weeks of age. It is concluded that dietary AA + DHA does not alter SPM cholesterol and phospholipid content but increases the 22:6n-3 content of SPM phospholipids modulating activity of Na,K-ATPase.
Topics: Administration, Oral; Age Factors; Animals; Cholesterol; Docosahexaenoic Acids; Enzyme Activation; Fatty Acids; Female; Food, Formulated; Gastrointestinal Contents; Growth; Male; Phosphatidylinositols; Phosphatidylserines; Phospholipids; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sex Factors; Sodium-Potassium-Exchanging ATPase; Synapses; Synaptic Membranes; alpha-Linolenic Acid
PubMed: 12421348
DOI: 10.1046/j.1471-4159.2002.01156.x -
Lipids in Health and Disease Oct 2022Although obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or...
BACKGROUND
Although obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or fresh faeces and metabolites in blood or urine contribute to obesity resistance; however, the microbiota or metabolites in the small intestine have not been extensively studied.
METHODS
To investigate the relationship between the microbiota or metabolites in the small intestine and susceptibility to obesity, eighty-eight male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish two models of obesity and obesity resistance. For further study, six mice were chosen from among the obesity models, and twelve mice were randomly chosen from among the obesity resistance models. After fasting plasma glucose and behavioural testing, the mice were fed in single cages for another 4 weeks to observe their weight and food intake. All mice were sacrificed at 20 weeks of age. Serum ALT, AST, HDL, LDL, TG and TC levels were measured using an automatic biochemical analyser. The microbiota and metabolites in the small intestine contents were analysed using 16 S sequencing and an ultrahigh-performance liquid chromatographic system, respectively. Transcripts in the jejunum were evaluated using full-length transcriptome sequencing and verified by qPCR.
RESULTS
The results showed that HFD induced depression and anxiety behaviours and higher fasting plasma glucose, ALT, AST, HDL, LDL, TG and TC levels in the obese mice; however, these levels were improved in obese resistance mice. The correlation analysis showed that the phosphatidylcholine, TG, and phosphatidylethanolamine levels were higher in obese mice and correlated positively with intestinal microflora (Desulfovibrio and Gemella) and the Cxcl10 gene. A higher abundance of Clostridium_sensu_stricto_1 in obesity-resistant mice correlated negatively with the metabolite contents (neuromedin N and enkephalin L) and Pck1 gene expression and correlated positively with certain metabolites (5-hydroxy-L-tryptophan, cinnamyl alcohol and 1 H-indole-3-acetamide) and genes expression (Gdf15, Igfbp6 and Spp1).
CONCLUSION
Clostridium_sensu_stricto_1, neuromedin N, enkephalin L, Pck1, 5-hydroxy-L-tryptophan, Cxcl10 and cinnamyl alcohol may be novel biomarkers in the small intestine for obesity/obesity resistance. These might be helpful for obesity prevention or for treating obese patients.
Topics: Animals; Biomarkers; Blood Glucose; Diet, High-Fat; Enkephalins; Intestine, Small; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Phosphatidylcholines; Phosphatidylethanolamines; Propanols; Tryptophan
PubMed: 36209126
DOI: 10.1186/s12944-022-01711-0 -
The Journal of Nutritional Biochemistry Dec 2021Folic acid-fortified foods and multi-vitamin supplements containing folic acid (FA) are widely used around the world, but the exact mechanisms/metabolic effects of FA...
Folic acid-fortified foods and multi-vitamin supplements containing folic acid (FA) are widely used around the world, but the exact mechanisms/metabolic effects of FA are not precisely identified. We have demonstrated that Ceramide Synthase 6 (CerS6) and C-ceramide mediate response to folate stress in cultured cells. Here we investigated the dietary FA effects on mouse liver metabolome, with a specific focus on sphingolipids, CerS6 and C-ceramide. Wild-type and CerS6 mice were fed FA-deficient, control, or FA over-supplemented diets for 4 weeks. After dietary treatment, liver concentrations of ceramides, sphingomyelins and hexosylceramides were measured by LC-MS/MS and complemented by untargeted metabolomic characterization of mouse livers. Our study shows that alterations in dietary FA elicit multiple sphingolipid responses mediated by CerS6 in mouse livers. Folic acid-deficient diet elevated C-, C- and C- but not C-ceramide in WT male and female mice. Additionally, FA over-supplementation increased multiple sphingomyelin species, including total sphingomyelins, in both sexes. Of note, concentrations of C- and C-ceramides and hexosylceramides were significantly higher in female livers than in male. The latter were increased by FD diet, with no difference between sexes in total pools of these sphingolipid classes. Untargeted liver metabolomic analysis concurred with the targeted measurements and showed broad effects of dietary FA and CerS6 status on multiple lipid classes including sex-specific effects on phosphatidylethanolamines and diacylglycerols. Our study demonstrates that both dietary FA and CerS6 status exhibit pleiotropic and sex-dependent effects on liver metabolism, including hepatic sphingolipids, diacylglycerols, long chain fatty acids, and phospholipids.
Topics: Animals; Apoptosis; Cell Line, Tumor; Ceramides; Chromatography, Liquid; Diet; Female; Folic Acid; Liver; Male; Metabolome; Mice; Oxidoreductases; Sex Factors; Sphingolipids; Sphingomyelins; Sphingosine N-Acyltransferase; Tandem Mass Spectrometry
PubMed: 34358645
DOI: 10.1016/j.jnutbio.2021.108832 -
The American Journal of Clinical... Jun 2019Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.
BACKGROUND
Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.
OBJECTIVE
The aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes.
METHODS
Plasma phospholipid fatty acids were profiled at 3 time-points (1993-1997, 1998-2000, 2004-2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n-3 polyunsaturated fatty acids (PUFAs), plant n-3 PUFA, n-6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs).
RESULTS
Adjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: -0.63%), even-chain SFAs (-0.05%), n-6 PUFAs (-0.25%), and TFAs (-7.84%). In contrast, concentrations increased for marine n-3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n-3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n-3 PUFAs.
CONCLUSIONS
Even-chain SFAs and TFAs declined and marine n-3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.
Topics: Adult; Aged; Diet; Europe; Fatty Acids; Feeding Behavior; Female; Humans; Male; Middle Aged; Nutrition Surveys; Phospholipids; Prospective Studies
PubMed: 30997506
DOI: 10.1093/ajcn/nqz030 -
Nutrients May 2011Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of... (Review)
Review
Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA), the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation.
Topics: Animals; Brain; Cell Membrane; Diet; Dietary Fats; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-6; Humans; Mental Disorders; Neurodegenerative Diseases; Nutritional Requirements; Phospholipids; alpha-Linolenic Acid
PubMed: 22254110
DOI: 10.3390/nu3050529