The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.
- Klíčová slova
- lipidome, lipids, n-3 fatty acids, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis,
- MeSH
- cholesterol metabolismus MeSH
- cholin metabolismus MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- játra metabolismus MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- kyseliny mastné omega-3 * farmakologie terapeutické užití metabolismus MeSH
- methionin metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * etiologie genetika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- Racemethionin metabolismus farmakologie MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- cholin MeSH
- kyseliny mastné neesterifikované MeSH
- kyseliny mastné omega-3 * MeSH
- methionin MeSH
- nenasycené mastné kyseliny MeSH
- Racemethionin MeSH
- triglyceridy MeSH
The unicellular green microalga Dunaliella is a potential source of a wide range of nutritionally important compounds applicable to the food industry. The aim of this study was to assess the effect of Dunaliella salina dried biomass on the growth and adherence of 10 strains of Lactobacillus, Lacticaseibacillus, and Bifidobacterium. The immunomodulatory, antioxidant, and cytotoxic effects of D. salina on human peripheral mononuclear cells and simulated intestinal epithelial cell lines Caco-2 and HT-29 were evaluated. Furthermore, the hypocholesterolemic effects of the microalgae on lipid metabolism in rats fed a high-fat diet were analyzed. The addition of D. salina biomass had a positive effect on the growth of nine out of 10 probiotics and promoted the adherence of three bifidobacteria strains to human cell lines. The antioxidant and immunomodulatory properties of D. salina were concentration-dependent. The inflammatory cytokines (TNF-α and IL-6) were significantly increased following Dunaliella stimulation at the lowest concentration (0.5% w/v). Eight week supplementation of D. salina to the diet of hypercholesteromic rats significantly decreased the serum concentrations of LDL-C, VLDL, IDL-B, and IDL-C. D. salina is not cytotoxic in intestinal cell models; it promotes adherence of selected bifidobacteria, it affords immunomodulatory and antioxidant effects, and its addition to diets may help decrease atherosclerosis risk factors.
- Klíčová slova
- Dunaliella salina, adherence, algae, cytokine, prebiotic,
- MeSH
- antioxidancia farmakologie metabolismus MeSH
- biomasa MeSH
- Caco-2 buňky MeSH
- Chlorophyceae * MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- mikrořasy * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia MeSH
INTRODUCTION: Monounsaturated fatty acids (MUFA) are understood to have therapeutic and preventive effects on chronic complications associated with type 2 diabetes mellitus (T2DM); however, there are differences between individual MUFAs. Although the effects of palmitoleic acid (POA) are still debated, POA can regulate glucose homeostasis, lipid metabolism, and cytokine production, thus improving metabolic disorders. In this study, we investigated and compared the metabolic effects of POA and oleic acid (OA) supplementation on glucose and lipid metabolism, insulin sensitivity, and inflammation in a prediabetic model, the hereditary hypertriglyceridemic rat (HHTg). HHTg rats exhibiting genetically determined hypertriglyceridemia, insulin resistance, and impaired glucose tolerance were fed a standard diet. POA and OA were each administered intragastrically at a dose of 100 mg/kg b.wt. for four weeks. RESULTS: Supplementation with both MUFAs significantly elevated insulin and glucagon levels, but only POA decreased nonfasting glucose. POA-treated rats showed elevated circulating NEFA associated with increased lipolysis, lipoprotein lipase gene expression, and fatty acid reesterification in visceral adipose tissue (VAT). The mechanism of improved insulin sensitivity of peripheral tissues (measured as insulin-stimulated lipogenesis and glycogenesis) in POA-treated HHTg rats could contribute increased circulating adiponectin and omentin levels together with elevated FADS1 gene expression in VAT. POA-supplemented rats exhibited markedly decreased proinflammatory cytokine production by VAT, which can alleviate chronic inflammation. OA-supplemented rats exhibited decreased arachidonic acid (AA) profiles and decreased proinflammatory AA-derived metabolites (20-HETE) in membrane phospholipids of peripheral tissues. Slightly increased FADS1 gene expression after OA along with increased adiponectin production by VAT was reflected in slightly ameliorated adipose tissue insulin sensitivity (increased insulin-stimulated lipogenesis). CONCLUSIONS: Our results show that POA served as a lipokine, ameliorating insulin sensitivity in peripheral tissue and markedly modulating the metabolic activity of VAT including cytokine secretion. OA had a beneficial effect on lipid metabolism and improved inflammation by modulating AA metabolism.
- MeSH
- adiponektin MeSH
- antiflogistika MeSH
- cytokiny MeSH
- diabetes mellitus 2. typu * MeSH
- glukagon MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence * MeSH
- krysa rodu Rattus MeSH
- kyselina olejová farmakologie MeSH
- kyseliny arachidonové MeSH
- kyseliny mastné mononenasycené farmakologie terapeutické užití MeSH
- kyseliny mastné neesterifikované MeSH
- lipoproteinlipasa MeSH
- mastné kyseliny metabolismus MeSH
- prediabetes * farmakoterapie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adiponektin MeSH
- antiflogistika MeSH
- cytokiny MeSH
- glukagon MeSH
- glukosa MeSH
- inzulin MeSH
- kyselina olejová MeSH
- kyseliny arachidonové MeSH
- kyseliny mastné mononenasycené MeSH
- kyseliny mastné neesterifikované MeSH
- lipoproteinlipasa MeSH
- mastné kyseliny MeSH
- palmitoleic acid MeSH Prohlížeč
Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.
- Klíčová slova
- FADS1, FADS2, cluster analysis, fatty acid pattern, haplotypes, metabolic syndrome, single-nucleotide polymorphism,
- Publikační typ
- časopisecké články MeSH
Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and β-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance.
- Klíčová slova
- chronic kidney disease, fatty acids, hemodialysis, hypolipidemic treatment, non-cholesterol sterols,
- Publikační typ
- časopisecké články MeSH
Polyunsaturated fatty acids (PUFA) influence many physiological functions. Associations have been found between single nucleotide polymorphisms (SNP) in the FADS1 (Fatty acid desaturase 1) gene and the relative abundance of PUFA in serum lipids. This study examines the relationship between two SNPs in the FADS1 gene (rs174546, rs174537) and the fatty acid (FA) composition of serum lipids in adolescents (13-18 years). We used DNA samples (670 children; 336 girls and 334 boys) from the Childhood Obesity Prevalence and Treatment (COPAT) project. Genomic DNA was extracted from peripheral blood leukocytes in whole blood samples. For genotype analysis, TaqMan SNP Genotyping assays (Applied Biosystems) were used. Fatty acid composition of serum lipids was assessed using gas chromatography. The T-statistic and regression were used for statistical evaluations. Minor allele T carriers in both SNPs had significant lower level of palmitic acid (16:0, phospholipids) and arachidonic acid (20:4[n-6], phospholipids) in both sexes. In girls, we found a significant positive association between minor allele T carriers and eicosadienoic acid (20:2[n-6], cholesteryl esters) in both SNPs. Being a minor allele T carrier was significantly positively associated with dihomo-γ-linolenic acid (20:3[n-6], phospholipids) in boys in both SNPs. SNPs (including rs174546, rs174537) in the FADS gene cluster should have impacted desaturase activity, which may contribute to different efficiency of PUFA synthesis.
- Klíčová slova
- FADS1, fatty acid, rs174537, rs174546, single nucleotide polymorphism,
- MeSH
- alely MeSH
- delta-5 desaturasa mastných kyselin MeSH
- desaturasy mastných kyselin genetika MeSH
- dítě MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mastné kyseliny * MeSH
- mladiství MeSH
- obezita dětí a dospívajících * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- delta-5 desaturasa mastných kyselin MeSH
- desaturasy mastných kyselin MeSH
- FADS1 protein, human MeSH Prohlížeč
- mastné kyseliny * MeSH
Background: Dysregulation of fatty acids (FA) seems to participate in the pathogenesis of disorders such as metabolic syndrome (MetS), cardiovascular diseases, or some cancers. Activities of enzymes FA desaturases and elongases [elongation of very long-chain fatty acid (ELOVL)] significantly influence FA profile in different body compartments. Although the impact of activities of desaturases on cardiometabolic diseases was broadly studied, relatively little attention was devoted to the role of elongases. Methods: Case-control study was carried out in 36 patients (18 men/18 women) with impaired fasting glycemia (IFG) without MetS and 36 age and gender-matched healthy controls. FA profiles in plasma phospholipids (PL) were assessed using gas chromatograph-flame ionization detector and indices of desaturase and elongase activities were calculated. Results: In the IFG group, we observed decreased estimated activities of ELOVL2 and ELOVL5, whereas higher estimated activities of elongase ELOVL6 were noted. IFG group was also characterized by altered composition of plasma PL FA, above all by lower percentage of cis-vaccenic acid (cVA; 18:1n-7) and of total polyunsaturated FA n-6, especially linoleic acid, and by higher proportion of stearic acid and gamma-linolenic acid. Concurrently, elevated estimated activities of desaturases delta-9-desaturase (D9D), D6D were found. Conclusions: Lower estimated activities of ELOVL2 and ELOVL5 with lowered proportion of PL cVA could be associated with disturbances of glucose homeostasis development and their corresponding indices could serve as biomarkers of such risk.
- Klíčová slova
- PUFA, fatty acid desaturases, fatty acid elongases, impaired fasting glycemia,
- MeSH
- elongasy mastných kyselin * krev MeSH
- krevní glukóza * analýza MeSH
- lidé MeSH
- metabolický syndrom epidemiologie MeSH
- omezení příjmu potravy * krev MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- elongasy mastných kyselin * MeSH
- krevní glukóza * MeSH
SCOPE: Infant formula (IF) uses besides vegetable fats also bovine milk fat, which differs in triacylglycerol (TAG) structure. Furthermore, it differs in fatty acid (FA) composition. Whether changing fat source in IF affects postprandial energy metabolism, lipemic response, and blood lipid profile is unknown. METHODS AND RESULTS: A proof-of-principle study, with a randomized controlled double-blind cross-over design, is conducted. Twenty healthy male adults consumed drinks with either 100% vegetable fat (VEG) or 67% bovine milk fat and 33% vegetable fat (BOV), on 2 separate days. For a detailed insight in the postprandial responses, indirect calorimetry is performed continuously, and venous blood samples are taken every 30 min, until 5 h postprandially. No differences in postprandial energy metabolism, serum lipids, lipoprotein, or chylomicron concentrations are observed between drinks. After consumption of VEG-drink, C18:2n-6 in serum increased. Observed differences in chylomicron FA profile reflect differences in initial FA profile of test drinks. Serum ketone bodies concentrations increase following consumption of BOV-drink. CONCLUSIONS: The use of bovine milk fat in IF does neither affect postprandial energy metabolism nor lipemic response in healthy adults, but alters postprandial FA profiles and ketone metabolism. Whether the exact same effects occur in infants requires experimental verification.
- Klíčová slova
- bovine milk fat, chylomicrons, infant formula, lipidomics, metabolism,
- MeSH
- chylomikrony krev MeSH
- dietní tuky * MeSH
- dvojitá slepá metoda MeSH
- energetický metabolismus * MeSH
- ketolátky krev MeSH
- klinické křížové studie MeSH
- kojenec MeSH
- lidé MeSH
- lipidy krev MeSH
- mastné kyseliny analýza MeSH
- metabolismus lipidů * MeSH
- mladý dospělý MeSH
- mléko * MeSH
- náhražky mateřského mléka * MeSH
- postprandiální období fyziologie MeSH
- zelenina MeSH
- zvířata MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- chylomikrony MeSH
- dietní tuky * MeSH
- ketolátky MeSH
- lipidy MeSH
- mastné kyseliny MeSH
The selenium (Se) enrichment of yeasts and lactic acid bacteria (LAB) has recently emerged as a novel concept; the individual health effects of these beneficial microorganisms are combined by supplying the essential micronutrient Se in a more bioavailable and less toxic form. This study investigated the bioavailability of Se in the strains Enterococcus faecium CCDM 922A (EF) and Streptococcus thermophilus CCDM 144 (ST) and their respective Se-enriched forms, SeEF and SeST, in a CD (SD-Sprague Dawley) IGS rat model. Se-enriched LAB administration resulted in higher Se concentrations in the liver and kidneys of rats, where selenocystine was the prevalent Se species. The administration of both Se-enriched strains improved the antioxidant status of the animals. The effect of the diet was more pronounced in the heart tissue, where a lower glutathione reductase content was observed, irrespective of the Se fortification in LAB. Interestingly, rats fed diets with EF and SeEF had higher glutathione reductase activity. Reduced concentrations of serum malondialdehyde were noted following Se supplementation. Diets containing Se-enriched strains showed no macroscopic effects on the liver, kidneys, heart, and brain and had no apparent influence on the basic parameters of the lipid metabolism. Both the strains tested herein showed potential for further applications as promising sources of organically bound Se and Se nanoparticles.
Omega-3 polyunsatuarted fatty acids (PUFA) are associated with hypolipidemic and anti-inflammatory effects. However, omega-3 PUFA, usually administered as triacylglycerols or ethyl esters, could also compromise glucose metabolism, especially in obese type 2 diabetics. Phospholipids represent an alternative source of omega-3 PUFA, but their impact on glucose homeostasis is poorly explored. Male C57BL/6N mice were fed for 8 weeks a corn oil-based high-fat diet (cHF) alone or cHF-based diets containing eicosapentaenoic acid and docosahexaenoic acid (~3%; wt/wt), admixed either as a concentrate of re-esterified triacylglycerols (ω3TG) or Krill oil containing mainly phospholipids (ω3PL). Lean controls were fed a low-fat diet. Insulin sensitivity (hyperinsulinemic-euglycemic clamps), parameters of glucose homeostasis, adipose tissue function, and plasma levels of N-acylethanolamines, monoacylglycerols and fatty acids were determined. Feeding cHF induced obesity and worsened (~4.3-fold) insulin sensitivity as determined by clamp. Insulin sensitivity was almost preserved in ω3PL but not ω3TG mice. Compared with cHF mice, endogenous glucose production was reduced to 47%, whereas whole-body and muscle glycogen synthesis increased ~3-fold in ω3PL mice that showed improved adipose tissue function and elevated plasma adiponectin levels. Besides eicosapentaenoic and docosapentaenoic acids, principal component analysis of plasma fatty acids identified palmitoleic acid (C16:1n-7) as the most discriminating analyte whose levels were increased in ω3PL mice and correlated negatively with the degree of cHF-induced glucose intolerance. While palmitoleic acid from Krill oil may help improve glucose homeostasis, our findings provide a general rationale for using omega-3 PUFA-containing phospholipids as nutritional supplements with potent insulin-sensitizing effects.
- Klíčová slova
- C57BL/6 mice, High-fat diet, Insulin resistance, Krill oil, Omega-3 PUFA, Palmitoleate,
- MeSH
- dieta s vysokým obsahem tuků MeSH
- fosfolipidy aplikace a dávkování metabolismus MeSH
- glukosa metabolismus MeSH
- homeostáza * MeSH
- inzulinová rezistence MeSH
- kyseliny mastné mononenasycené krev MeSH
- myši inbrední C57BL MeSH
- myši obézní MeSH
- myši MeSH
- oleje rostlin metabolismus MeSH
- potravní doplňky MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fosfolipidy MeSH
- glukosa MeSH
- kyseliny mastné mononenasycené MeSH
- oleje rostlin MeSH
- palmitoleic acid MeSH Prohlížeč
