Omega-3 polyunsaturated fatty acids (ω-3PUFAs) are introduced into parenteral nutrition (PN) as hepatoprotective but may be susceptible to the lipid peroxidation while olive oil (OO) is declared more peroxidation resistant. We aimed to estimate how the lipid composition of PN mixture affects plasma and erythrocyte lipidome and the propensity of oxidative stress. A cross-sectional comparative study was performed in a cohort of adult patients who were long-term parenterally administered ω-3 PUFAs without (FO/-, n = 9) or with (FO/OO, n = 13) olive oil and healthy age- and sex-matched controls, (n = 30). Lipoperoxidation assessed as plasma and erythrocyte malondialdehyde content was increased in both FO/- and FO/OO groups but protein oxidative stress (protein carbonyls in plasma) and low redox status (GSH/GSSG in erythrocytes) was detected only in the FO/- subcohort. The lipidome of all subjects receiving ω-3 PUFAs was enriched with lipid species containing ω-3 PUFAs (FO/-˃FO/OO). Common characteristic of all PN-dependent patients was high content of fatty acyl-esters of hydroxy-fatty acids (FAHFAs) in plasma while acylcarnitines and ceramides were enriched in erythrocytes. Plasma and erythrocyte concentrations of plasmanyls and plasmalogens (endogenous antioxidants) were decreased in both patient groups with a significantly more pronounced effect in FO/-. We confirmed the protective effect of OO in PN mixtures containing ω-3 PUFAs.
- MeSH
- Antioxidants metabolism MeSH
- Adult MeSH
- Erythrocytes metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipidomics MeSH
- Lipids blood MeSH
- Intestinal Diseases blood therapy MeSH
- Olive Oil pharmacology MeSH
- Fatty Acids, Omega-3 pharmacology MeSH
- Oxidative Stress drug effects MeSH
- Parenteral Nutrition adverse effects methods MeSH
- Cross-Sectional Studies MeSH
- Fish Oils pharmacology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Fat Emulsions, Intravenous pharmacology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Recent evidence has raised the possibility of the existence of a sixth taste modality - that is, taste for fat - which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.
- MeSH
- CD36 Antigens genetics MeSH
- Taste genetics MeSH
- Taste Perception genetics MeSH
- Dietary Fats MeSH
- Adult MeSH
- Genotype * MeSH
- Body Mass Index MeSH
- Polymorphism, Single Nucleotide * MeSH
- Linoleic Acid * MeSH
- Humans MeSH
- Young Adult MeSH
- Obesity genetics MeSH
- Waist Circumference MeSH
- Waist-Height Ratio MeSH
- Food Preferences physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.
- MeSH
- Alleles MeSH
- CD36 Antigens genetics MeSH
- Taste Perception MeSH
- Taste Buds MeSH
- Taste Threshold * MeSH
- Diet MeSH
- Dietary Fats * MeSH
- Gene Frequency MeSH
- Genotype MeSH
- Glycoproteins genetics MeSH
- Thinness genetics MeSH
- Body Mass Index * MeSH
- Polymorphism, Single Nucleotide * MeSH
- Oleic Acid MeSH
- Humans MeSH
- Adolescent MeSH
- Obesity etiology genetics MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Algeria MeSH
BACKGROUND: Therapeutic options for atopic dermatitis mostly address the symptoms but causal therapies are still missing. Peroxisome proliferator activated receptor (PPAR) agonists exert beneficial effects in patients suffering this disease, whereas the stimulation of PPARα and γ seemed most promising. OBJECTIVES: To elucidate the effects of the PPARα specific agonist WY14643, the PPARγ agonist ciglitazone, and the dual PPARα+γ agonist docosahexaenoic acid (DHA) on the homeostasis and barrier function of filaggrin deficient skin. METHODS: The effects of the PPAR agonists on skin differentiation were evaluated via qPCR, Western blot, histological or immunofluorescence staining. Skin lipid organization was determined by ATR-FTIR and lipid composition was analyzed by HPTLC. Ultimately, the skin barrier function was assessed by skin absorption studies using the radioactively labeled compound testosterone. RESULTS: Significant upregulation of filaggrin after DHA and WY14643 supplementation, but no effect of ciglitazone, on protein and mRNA level was detected. DHA and WY14643, but not ciglitazone, normalized the molar ratio of the main skin barrier lipids to 1:1:1 (free fatty acids:ceramides:cholesterol). Furthermore, DHA and WY14643 supplementation normalized the skin lipid profile in filaggrin deficient skin, but only WY14643 significantly improved the skin barrier function. CONCLUSION: Supplementation particularly with the PPARα agonist WY14643 improved the homeostasis and barrier function of filaggrin deficient skin models by normalization of the free fatty acid profile underlining the potential of PPAR agonists for the treatment of filaggrin-associated skin diseases.
- MeSH
- Time Factors MeSH
- Phenotype MeSH
- Fibroblasts drug effects metabolism MeSH
- Genotype MeSH
- Skin Absorption drug effects MeSH
- Cells, Cultured MeSH
- Skin drug effects metabolism MeSH
- Docosahexaenoic Acids pharmacology MeSH
- Fatty Acids, Nonesterified metabolism MeSH
- Humans MeSH
- Membrane Proteins genetics metabolism MeSH
- Lipid Metabolism drug effects MeSH
- Permeability MeSH
- PPAR alpha agonists metabolism MeSH
- PPAR gamma agonists metabolism MeSH
- Protein Precursors genetics metabolism MeSH
- Intermediate Filament Proteins deficiency genetics MeSH
- Pyrimidines pharmacology MeSH
- RNA Interference MeSH
- Signal Transduction drug effects MeSH
- Testosterone metabolism MeSH
- Thiazolidinediones pharmacology MeSH
- Transfection MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Transgenic APPswe/PS1dE9 mice modeling Alzheimer's disease demonstrate ongoing accumulation of β-amyloid fragments resulting in formation of amyloid plaques that starts at the age of 4-5 months. Buildup of β-amyloid fragments is accompanied by impairment of muscarinic transmission that becomes detectable at this age, well before the appearance of cognitive deficits that manifest around the age of 12 months. We have recently demonstrated that long-term feeding of trangenic mice with specific isocaloric fish oil-based diets improves specific behavioral parameters. Now we report on the influence of short-term feeding (3 weeks) of three isocaloric diets supplemented with Fortasyn (containing fish oil and ingredients supporting membrane renewal), the plant sterol stigmasterol together with fish oil, and stigmasterol alone on markers of cholinergic neurotransmission in the hippocampus of 5-month-old transgenic mice and their wild-type littermates. Transgenic mice fed normal diet demostrated increase in ChAT activity and attenuation of carbachol-stimulated GTP-γ(35)S binding compared to wild-type mice. None of the tested diets compared to control diet influenced the activities of ChAT, AChE, BuChE, muscarinic receptor density or carbachol-stimulated GTP-γ(35)S binding in wild-type mice. In contrast, all experimental diets increased the potency of carbachol in stimulating GTP-γ(35)S binding in trangenic mice to the level found in wild-type animals. Only the Fortasyn diet increased markers of cholinergic synapses in transgenic mice. Our data demonstrate that even short-term feeding of transgenic mice with chow containing specific lipid-based dietary supplements can influence markers of cholinergic synapses and rectify impaired muscarinic signal transduction that develops in transgenic mice.
- MeSH
- Alzheimer Disease diet therapy physiopathology MeSH
- Amyloid beta-Protein Precursor genetics metabolism MeSH
- Dietary Fats administration & dosage MeSH
- Hippocampus physiopathology MeSH
- Caspase 8 metabolism MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C3H MeSH
- Mice, Inbred C57BL MeSH
- Mice, Transgenic MeSH
- Synaptic Transmission physiology MeSH
- Presenilin-1 genetics metabolism MeSH
- Receptors, Muscarinic metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Recent studies have suggested that excessive intake of dietary fat is associated with obesity. Some obese subjects have been reported to exhibit high thresholds for the gustatory detection of lipids via lipid receptors, such as cluster of differentiation 36 (CD36). We studied lingual detection thresholds for emulsions containing oleic acid in obese Tunisian women (n 203) using a three-alternative forced choice (3-AFC) method. Genotyping of the TNF-α (rs1800629), IL-6 (rs1800795) and CD36 (rs1761667) genes was performed to associate with lipid taste perception thresholds. The CD36 genotype distribution was as follows: GG (n 42), AG (n 102) and AA (n 59). Women with the CD36 GG genotype exhibited oral detection thresholds for oleic acid that were more than three times lower than those with the CD36 AA genotype. The present study confirms a high threshold of gustatory fat detection in obese women with the CD36 AA genotype, but there is no significant association with the IL-6 and TNF-α gene polymorphisms.
- MeSH
- Alleles MeSH
- CD36 Antigens genetics MeSH
- Administration, Oral MeSH
- Taste genetics MeSH
- Taste Perception genetics MeSH
- Taste Buds physiology MeSH
- Dietary Fats * MeSH
- Adult MeSH
- Genotype MeSH
- Interleukin-6 blood MeSH
- Polymorphism, Single Nucleotide MeSH
- Oleic Acid chemistry MeSH
- Middle Aged MeSH
- Humans MeSH
- Obesity physiopathology MeSH
- Food Preferences MeSH
- Cluster Analysis MeSH
- Tumor Necrosis Factor-alpha genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Tunisia MeSH
BACKGROUND/OBJECTIVE: Obesity is an alarming threat for all age groups, including children. Fat overconsumption is one of the factors that directly influences this pathology. Recent studies have suggested that a common variant in the CD36 gene, that is, single-nucleotide polymorphism (SNP) rs1761667-A allele, that reduces CD36 expression, associates with high oral fat detection thresholds in some obese subjects. The objective was to assess fatty acid sensitivity in relation to CD36 SNP in young lean and obese children. SUBJECTS/METHODS: We studied lingual detection thresholds for emulsions, containing oleic acid, in Algerian children (n=116, age=8±0.5 years) who were divided into two groups: obese (n=57; body mass index (BMI) z-score=2.513±0.490) and lean children (n=59; BMI z-score=-0.138±0.601) by alternative-forced choice method. To correlate the lipid taste perception thresholds with CD36 SNP, the children were genotyped for A/G SNP rs1761667 in 5'UTR region of CD36 by using PCR and restriction fragment length polymorphism. RESULTS: We noticed significantly higher CD36 A-allele frequency (P=0.036) in young obese children compared with leans. CD36 A-allele was associated with higher lipid taste perception thresholds than G-allele in obese children, but not in lean controls. Moreover, waist circumference was positively correlated with reduced fat taste sensitivity in these children. CONCLUSIONS: CD36 SNP A-allele, being present both in young lean and in obese children, is associated with high threshold for fatty acid taste sensitivity only in obese children.
- MeSH
- CD36 Antigens genetics MeSH
- Taste Perception genetics MeSH
- Dietary Fats MeSH
- Child MeSH
- Gene Frequency MeSH
- Genotype MeSH
- Thinness genetics metabolism MeSH
- Body Mass Index MeSH
- Polymorphism, Single Nucleotide * MeSH
- Oleic Acid metabolism MeSH
- Humans MeSH
- Obesity genetics metabolism MeSH
- Waist Circumference MeSH
- Food Preferences MeSH
- Surveys and Questionnaires MeSH
- Feeding Behavior MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Algeria MeSH
OBJECTIVES: The aim of this study was to investigate whether rosuvastatin affects expression and activity of rat CYP2C6. This cytochrome P450 is considered to be a counterpart of human CYP2C9, which metabolizes many drugs, including diclofenac, ibuprofen or warfarin. DESIGN: Male hereditary hypertriglyceridemic (HHTg) rats were fed standard laboratory diet (STD) or high cholesterol diet (HCD: STD + 1% of cholesterol w/w + 10% of lard fat w/w) for 21 days. A third group of rats were fed high a cholesterol diet with rosuvastatin added (0.03% w/w). Expression of CYP2C6 was measured in liver samples using real-time PCR (mRNA level) and Western blotting (protein level). Formation of diclofenac metabolites (typical enzyme activity of CYP2C6) was analyzed using HPLC with UV detection. RESULTS: Administration of rosuvastatin to HHTg rats resulted in significantly increased mRNA expression and enzyme activity in HCD-fed animals; changes of CYP2C6 protein were non-significant. These results suggest that CYP2C6 expression and activity are positively affected by rosuvastatin in hereditary hypertriglyceridemic rats after intake of HCD. CONCLUSION: The results presented open the possibility that in humans, rosuvastatin may affect the metabolism of many drugs by influencing expression and activity of CYP2C6 (counterpart of human CYP2C9). Further studies are needed to elucidate the effects of this statin on CYP2C9 in humans.
- MeSH
- Aryl Hydrocarbon Hydroxylases antagonists & inhibitors metabolism MeSH
- Cholesterol, Dietary pharmacology MeSH
- Fluorobenzenes pharmacology MeSH
- Transcription, Genetic drug effects MeSH
- Hyperlipoproteinemia Type IV drug therapy genetics metabolism MeSH
- Microsomes, Liver drug effects enzymology MeSH
- Rats MeSH
- Humans MeSH
- RNA, Messenger metabolism MeSH
- Rats, Mutant Strains MeSH
- Rats, Wistar MeSH
- Pyrimidines pharmacology MeSH
- Gene Expression Regulation, Enzymologic drug effects MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology MeSH
- Steroid 21-Hydroxylase antagonists & inhibitors genetics metabolism MeSH
- Sulfonamides pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Omega-3 fatty acids (FA) have been shown to be protective against cardiovascular diseases (CVD). The effect of the consumption of carp meat on CVD risk factors has not yet been examined in detail. We ascertained the influence of a diet enriched with carp meat with an elevated content of omega-3FA (200 g twice weekly for 4 weeks) in a group of subjects after cardiac revascularization surgery for ischemic heart disease with a follow-up spa treatment. DESIGN: After cardiac revascularization surgery, the probands consumed either a standard spa diet (56 individuals, 41 males, 15 females, age 41-80 years) or a diet enriched with two portions of carp meat (87 individuals, 64 males, 23 females, age 50-82 years). The differences in body mass index (kg/m²), blood pressure, plasma lipids and C-reactive protein (CRP) of the groups were analyzed. RESULTS: In the group with a higher consumption of carp meat, significantly greater improvements in lipid parameters in comparison to the standard spa diet were detected (total cholesterol p<0.001, triglycerides p<0.001, LDL-C p<0.001, CRP p<0.001, HDL-C p<0.001). No differences between these groups in blood pressure and body mass index were found. CONCLUSION: We conclude that the diet enriched with carp meat significantly improved plasma lipid parameters in patients after major cardiac revascularization surgery.
- MeSH
- C-Reactive Protein metabolism MeSH
- Diet MeSH
- Adult MeSH
- Cholesterol, HDL blood MeSH
- Body Mass Index MeSH
- Myocardial Ischemia diet therapy prevention & control surgery MeSH
- Carps MeSH
- Blood Pressure physiology MeSH
- Cholesterol, LDL blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipids blood MeSH
- Meat MeSH
- Fatty Acids, Omega-3 blood MeSH
- Recurrence MeSH
- Myocardial Revascularization MeSH
- Secondary Prevention methods MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
AIMS/HYPOTHESIS: Intake of n-3 polyunsaturated fatty acids reduces adipose tissue mass, preferentially in the abdomen. The more pronounced effect of marine-derived eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on adiposity, compared with their precursor alpha-linolenic acid, may be mediated by changes in gene expression and metabolism in white fat. METHODS: The effects of EPA/DHA concentrate (6% EPA, 51% DHA) admixed to form two types of high-fat diet were studied in C57BL/6J mice. Oligonucleotide microarrays, cDNA PCR subtraction and quantitative real-time RT-PCR were used to characterise gene expression. Mitochondrial proteins were quantified using immunoblots. Fatty acid oxidation and synthesis were measured in adipose tissue fragments. RESULTS: Expression screens revealed upregulation of genes for mitochondrial proteins, predominantly in epididymal fat when EPA/DHA concentrate was admixed to a semisynthetic high-fat diet rich in alpha-linolenic acid. This was associated with a three-fold stimulation of the expression of genes encoding regulatory factors for mitochondrial biogenesis and oxidative metabolism (peroxisome proliferator-activated receptor gamma coactivator 1 alpha [Ppargc1a, also known as Pgc1alpha] and nuclear respiratory factor-1 [Nrf1] respectively). Expression of genes for carnitine palmitoyltransferase 1A and fatty acid oxidation was increased in epididymal but not subcutaneous fat. In the former depot, lipogenesis was depressed. Similar changes in adipose gene expression were detected after replacement of as little as 15% of lipids in the composite high-fat diet with EPA/DHA concentrate, while the development of obesity was reduced. The expression of Ppargc1a and Nrf1 was also stimulated by n-3 polyunsaturated fatty acids in 3T3-L1 cells. CONCLUSIONS/INTERPRETATION: The anti-adipogenic effect of EPA/DHA may involve a metabolic switch in adipocytes that includes enhancement of beta-oxidation and upregulation of mitochondrial biogenesis.
- MeSH
- Epididymis metabolism drug effects MeSH
- NF-E2-Related Factor 1 genetics drug effects MeSH
- Carnitine O-Palmitoyltransferase genetics drug effects MeSH
- Cells, Cultured MeSH
- alpha-Linolenic Acid pharmacology MeSH
- Eicosapentaenoic Acid pharmacology MeSH
- Docosahexaenoic Acids pharmacology MeSH
- Lipogenesis radiation effects MeSH
- Mitochondrial Proteins metabolism drug effects MeSH
- Mitochondria metabolism drug effects MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Fatty Acids, Unsaturated pharmacology isolation & purification metabolism MeSH
- Obesity prevention & control MeSH
- Oxidation-Reduction MeSH
- Subcutaneous Fat metabolism drug effects MeSH
- Gene Expression Regulation radiation effects MeSH
- Fish Oils chemistry MeSH
- Trans-Activators genetics drug effects MeSH
- Adipose Tissue metabolism drug effects MeSH
- Adipocytes metabolism drug effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH