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Nutrients Aug 2023This feeding trial evaluated the impact of the Dietary Approaches to Stop Hypertension diet on changes in plasma choline, choline metabolites, and ceramides in obese... (Clinical Trial)
Clinical Trial
This feeding trial evaluated the impact of the Dietary Approaches to Stop Hypertension diet on changes in plasma choline, choline metabolites, and ceramides in obese older adults; 28 adults consumed 3oz (n = 15) or 6oz (n = 13) of beef within a standardized DASH diet for 12 weeks. Plasma choline, betaine, methionine, dimethylglycine (DMG), phosphatidylcholine (PC), lysophosphotidylcholine (LPC), sphingomyelin, trimethylamine-N-oxide (TMAO), L-carnitine, ceramide, and triglycerides were measured in fasted blood samples. Plasma LPC, sphingomyelin, and ceramide species were also quantified. In response to the study diet, with beef intake groups combined, plasma choline decreased by 9.6% ( = 0.012); DMG decreased by 10% ( = 0.042); PC decreased by 51% ( < 0.001); total LPC increased by 281% ( < 0.001); TMAO increased by 26.5% ( < 0.001); total ceramide decreased by 22.1% ( < 0.001); and triglycerides decreased by 18% ( = 0.021). All 20 LPC species measured increased ( < 0.01) with LPC 16:0 having the greatest response. Sphingomyelin 16:0, 18:0, and 18:1 increased (all < 0.001) by 10.4%, 22.5%, and 24%, respectively. In contrast, we observed that sphingomyelin 24:0 significantly decreased by 10%. Ceramide 22:0 and 24:0 decreased by 27.6% and 10.9% ( < 0.001), respectively, and ceramide 24:1 increased by 36.8% ( = 0.013). Changes in choline and choline metabolites were in association with anthropometric and cardiometabolic outcomes. These findings show the impact of the DASH diet on choline metabolism in older adults and demonstrate the influence of diet to modify circulating LPC, sphingomyelin, and ceramide species.
Topics: Aged; Humans; Ceramides; Choline; Dietary Approaches To Stop Hypertension; Lecithins; Meat; Sphingomyelins
PubMed: 37686719
DOI: 10.3390/nu15173687 -
Aging Jul 2023In this study we sought to analyze the critical role of oxidized phospholipid (OxPL) in the progression of calcific aortic valve disease (CAVD) with the involvement of...
In this study we sought to analyze the critical role of oxidized phospholipid (OxPL) in the progression of calcific aortic valve disease (CAVD) with the involvement of activating transcription factor 4 (ATF4). Differentially expressed genes related to CAVD were identified using bioinformatics analysis. Expression of ATF4 was examined in mouse models of aortic valve calcification (AVC) induced by the high cholesterol (HC) diet. Valvular interstitial cells (VICs) were then isolated from mouse non-calcified valve tissues, induced by osteogenic induction medium (OIM) and co-cultured with OxPAPC-stimulated macrophages. The effect of OxPLs regulating ATF4 on the macrophage polarization and osteogenic differentiation of VICs was examined with gain- and loss-of-function experiments in VICs and . In aortic valve tissues and OIM-induced VICs, ATF4 was highly expressed. ATF4 knockdown alleviated the osteogenic differentiation of VICs, as evidenced by reduced expression of bone morphogenetic protein-2 (BMP2), osteopontin (OPN), and osteocalcin. In addition, knockdown of ATF4 arrested the AVC . Meanwhile, OxPL promoted M1 polarization of macrophages and mediated osteogenic differentiation of VICs. Furthermore, OxPL up-regulated ATF4 expression through protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 subunit alpha (eIF2α) pathway. In conclusion, OxPL can potentially up-regulate the expression of ATF4, inducing macrophages polarized to M1 phenotype, osteogenic differentiation of VICs and AVC, thus accelerating the progression of CAVD.
Topics: Animals; Mice; Activating Transcription Factor 4; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Cell Differentiation; Cells, Cultured; Endoplasmic Reticulum; Eukaryotic Initiation Factor-2; Osteogenesis; Phospholipids; Protein Kinases
PubMed: 37462732
DOI: 10.18632/aging.204875 -
Food Chemistry Jul 2024Human milk, which contains various nutrients, is the "gold standard" for infant nutrition. Healthy human milk meets all the nutritional needs of early infant... (Review)
Review
Human milk, which contains various nutrients, is the "gold standard" for infant nutrition. Healthy human milk meets all the nutritional needs of early infant development. Polar lipids mainly exist in the milk fat globule membrane, accounting for approximately 1-2% of human milk lipids; sphingomyelin (SM) accounts for approximately 21-24% of polar lipids. SM plays an important role in promoting the development of the brain and nervous system, regulating intestinal flora, and improving skin barriers. Though SM could be synthesized de novo, SM nutrition from dietary is also important for infants. The content and composition of SM in human milk has been reported, however, the molecular mechanisms of nutritional functions of SM for infants required further research. This review summarizes the functional mechanisms, metabolic pathways, and compositional, influencing factors, and mimicking of SM in human milk, and highlights the challenges of improving maternal and infant early/long-term nutrition.
Topics: Infant; Child; Humans; Sphingomyelins; Milk, Human; Diet; Nutritional Status; Infant Nutritional Physiological Phenomena
PubMed: 38520905
DOI: 10.1016/j.foodchem.2024.138991 -
Biochimica Et Biophysica Acta.... Aug 2023Ceramides (Cer) have been shown as lipotoxic inducers, which disturb numerous cell-signaling pathways, leading to metabolic disorders such as type 2 diabetes. In this...
Ceramides (Cer) have been shown as lipotoxic inducers, which disturb numerous cell-signaling pathways, leading to metabolic disorders such as type 2 diabetes. In this study, we aimed to determine the role of de novo hepatic ceramide synthesis in energy and liver homeostasis in mice. We generated mice lacking serine palmitoyltransferase 2 (Sptlc2), the rate limiting enzyme of ceramide de novo synthesis, in liver under albumin promoter. Liver function, glucose homeostasis, bile acid (BA) metabolism and hepatic sphingolipids content were assessed using metabolic tests and LC-MS. Despite lower expression of hepatic Sptlc2, we observed an increased concentration of hepatic Cer, associated with a 10-fold increase in neutral sphingomyelinase 2 (nSMase2) expression, and a decreased sphingomyelin content in the liver. Sptlc2 mice were protected against obesity induced by high fat diet and displayed a defect in lipid absorption. In addition, an important increase in tauro-muricholic acid was associated with a downregulation of the nuclear BA receptor FXR target genes. Sptlc2 deficiency also enhanced glucose tolerance and attenuated hepatic glucose production, while the latter effect was dampened in presence of nSMase2 inhibitor. Finally, Sptlc2 disruption promoted apoptosis, inflammation and progressive development of hepatic fibrosis, worsening with age. Our data suggest a compensatory mechanism to regulate hepatic ceramides content from sphingomyelin hydrolysis, with deleterious impact on liver homeostasis. In addition, our results show the involvement of hepatic sphingolipid modulation in BA metabolism and hepatic glucose production in an insulin-independent manner, which highlight the still under-researched role of ceramides in many metabolic functions.
Topics: Animals; Mice; Bile Acids and Salts; Ceramides; Diabetes Mellitus, Type 2; Glucose; Homeostasis; Liver; Serine; Serine C-Palmitoyltransferase; Sphingolipids; Sphingomyelins
PubMed: 37224999
DOI: 10.1016/j.bbalip.2023.159333 -
Foods (Basel, Switzerland) Aug 2023Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a...
Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a plasmalogen-rich resource, this study aimed to explore its potential for plasmalogen-based health food product development, with special attention on whether and how the industrial production processes influence the plasmalogen content and composition. In the present work, plasmalogens from different porcine brain products were investigated using liquid chromatography-tandem mass spectrometry. The results indicated that all the porcine brain products showed abundant total plasmalogens, of which more than 95% were ethanolamine plasmalogen species. Acetone precipitation, ethanol extraction, and drying did not significantly affect the plasmalogen content, whereas repeated freeze-thaw cycles in the production process led to noticeable loss. The chemometric investigation suggested that raw products and glycerophospholipid products exhibited different profiles; furthermore, the concentration step seemed to impact the plasmalogen composition. The nutritional assessment revealed that porcine brain products showed favorable values of multiple indexes, including PUFA/SFA ratio, n-6/n-3 ratio, thrombogenicity index, and unsaturation index, suggesting a health-beneficial value. The current study not only shows the feasibility of producing porcine brain-derived plasmalogens, but also provides possible strategies for developing and quality-controlling dietary plasmalogen supplements and healthcare products.
PubMed: 37627989
DOI: 10.3390/foods12162990 -
Scientific Reports Oct 2023Intermittent fasting (IF) is associated with enormous metabolic alterations that underpin its diverse health effects. Changes in lipid metabolism, particularly...
Ramadan intermittent fasting is associated with ameliorated inflammatory markers and improved plasma sphingolipids/ceramides in subjects with obesity: lipidomics analysis.
Intermittent fasting (IF) is associated with enormous metabolic alterations that underpin its diverse health effects. Changes in lipid metabolism, particularly ceramides, and other sphingolipids, are among the most notable of these alterations. This study investigated the lipidomic alterations associated with 29-30 days of Ramadan diurnal intermittent fasting (RIF) in metabolically healthy overweight and obese subjects. A prospective cohort of 57 overweight and obese adults (70% males, 38.4 ± 11.2 years), with an age range of 18-58 years was observed prior to and at the conclusion of Ramadan. At both time points, anthropometric, biochemical (lipid profile, glycemic, and inflammatory markers), and dietary intake measurements were taken. Using liquid chromatography-mass spectrometry, a lipidomic analysis of ceramides and other sphingolipids was conducted. Using paired sample t-tests, pre- and post-Ramadan anthropometric, biochemical, and dietary values were compared. RIF was associated with improved levels of lipid profile compartments and inflammatory markers. In addition, RIF was associated with a decrease in plasma sphingosine and sphinganine, which was accompanied by a decrease in sphingosine 1-phosphate and sphinganine 1-phosphate. In addition, RIF was associated with decreased C17, C22, and C24 sphingomyelin, but not C14, C16, C18, C20, and C24:1 sphingomyelin, as well as C20, C22, C24, and C24:1 dihydrosphingomyelin, but not C16 and C18 dihydrosphingomyelin. This study demonstrates that RIF is associated with improvements in plasma sphingosine, sphinganine sphingomyelin, and dihydrosphingomyelin lipid species, as well as improved lipid profile and inflammatory markers, which may confer short-term protection against cardiometabolic problems in patients with overweight/obesity.
Topics: Male; Adult; Humans; Adolescent; Young Adult; Middle Aged; Female; Sphingolipids; Ceramides; Sphingomyelins; Sphingosine; Overweight; Lipidomics; Intermittent Fasting; Prospective Studies; Obesity; Fasting
PubMed: 37833312
DOI: 10.1038/s41598-023-43862-9 -
Medicina (Kaunas, Lithuania) Aug 2023Dietary fats are essential for maternal and fetal health. Fatty acids (FAs) in erythrocytes characterize the FA profile, which is influenced by diet and other factors....
BACKGROUND AND OBJECTIVES
Dietary fats are essential for maternal and fetal health. Fatty acids (FAs) in erythrocytes characterize the FA profile, which is influenced by diet and other factors. The aim of this study was to evaluate the association between the main FAs in erythrocyte membrane phospholipids and their influencing factors-dietary fat and supplement intake and lifestyle factors-in Latvian pregnant women.
MATERIALS AND METHODS
This cross-sectional study included 236 pregnant and postpartum women. The data were collected from medical documentation, a food frequency questionnaire, and a questionnaire on demographic, lifestyle, health status, and nutritional habits in outpatient clinics and maternity departments. FAs in erythrocyte membrane phospholipids were determined using gas chromatography.
RESULTS
Correlations were found between dietary SFAs and erythrocyte SFAs (r = -0.140, = 0.032) and PUFAs (r = 0.167, = 0.01) and between dietary PUFAs and erythrocyte MUFAs (r = -0.143, = 0.028). Dietary SFAs, MUFAs, and PUFAs positively correlated with the studied n-3 and n-6 FAs in erythrocytes. Vitamin D correlated positively with MUFA and negatively with total PUFA and AA in erythrocytes. There was a negative correlation between dietary vitamin A and linoleic acid in erythrocytes. Physical activity negatively correlated with erythrocyte MUFAs and positively with erythrocyte PUFAs. Alcohol consumption positively correlated with erythrocyte SFAs and negatively with erythrocyte PUFAs.
CONCLUSIONS
There are indications that some dietary FAs may be correlated with erythrocyte FAs. Possible influencing factors for this association are alcohol, physical activity, vitamin D, and vitamin A.
Topics: Pregnancy; Female; Humans; Fatty Acids; Phospholipids; Vitamin A; Cross-Sectional Studies; Latvia; Pregnant Women; Diet; Erythrocytes; Vitamin D; Vitamins; Dietary Fats
PubMed: 37763633
DOI: 10.3390/medicina59091514 -
The Journal of Steroid Biochemistry and... Oct 2023Vitamin D is found in two forms in humans, D3 produced in the skin and D2 solely from the diet. Both 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D...
Vitamin D is found in two forms in humans, D3 produced in the skin and D2 solely from the diet. Both 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D) are oxidised and inactivated by CYP24A1, a tightly regulated mitochondrial enzyme that controls serum levels of these secosteroids. The pathways of oxidation of 25(OH)D2 and 1,25(OH)D2, particularly 25(OH)D2, by human CYP24A1 are not well characterized. The aim of this study was to further elucidate these pathways, and to compare the kinetics of metabolism of 25(OH)D2 and 1,25(OH)D2 with their vitamin D3 counterparts. We used expressed and partially purified human CYP24A1 with substrates dissolved in the membrane of phospholipid vesicles, to mimic the inner mitochondrial membrane. We found that the major pathways for side chain oxidation of 25(OH)D2 and 1,25(OH)D2 were identical and that predominant intermediates of 25(OH)D2 metabolism could be converted to the corresponding intermediates in the pathway of 1,25(OH)D2 oxidation by 1α-hydroxylation by CYP27B1. The initial steps in the CYP24A1-mediated oxidation involved hydroxylation at the C24R position, and another unknown position where the alcohol was oxidised to an aldehyde. The 24R-hydroxylation was followed by hydroxylation at C26 or C28, or cleavage between C24 and C25 to produce the 24-oxo-25,26,27-trinor derivative. All of these products were further oxidised, with 24-oxo-25,26,27-trinor-1(OH)D2 giving a product tentatively identified as 24-oxo-25,26,27-trinor-1,28(OH)D2. The catalytic efficiency (k/K) of CYP24A1 for initial 25(OH)D2 hydroxylation was similar to that for 25(OH)D3, indicating that they have similar rates of inactivation at low substrate concentrations, supporting that vitamins D2 and D3 are equally effective in maintaining serum 25(OH)D concentrations. In contrast, the k/K value for 1,25(OH)D3 was almost double that for 1,25(OH)D2 indicating a lower rate of inactivation of 1,25(OH)D2 at a low substrate concentration, suggesting that it has increased metabolic stability in vivo.
Topics: Humans; Calcifediol; Cholecalciferol; Ergocalciferols; Vitamin D; Vitamin D3 24-Hydroxylase
PubMed: 37495192
DOI: 10.1016/j.jsbmb.2023.106368 -
Journal of the American Heart... Jun 2024Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is... (Review)
Review
Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes. Apolipoprotein(a) is encoded by the gene and contains 10 subtypes with a variable number of copies of kringle -2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond , such as and , have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3-fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the promoter contains an interleukin-6 response element; interleukin-6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA-targeted agents have shown promising lipoprotein(a)-lowering effects in clinical studies, and large-scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.
Topics: Humans; Lipoprotein(a); Cardiovascular Diseases; Heart Disease Risk Factors; Genetic Predisposition to Disease; Risk Assessment; Phenotype
PubMed: 38879448
DOI: 10.1161/JAHA.123.033654 -
Current Aging Science 2024Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative...
BACKGROUND
Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS. The results of different studies over the past decades have established the protective effect of NAE on many pathological conditions.
OBJECTIVE
This study aimed to investigate the cardioprotective effects of C18:0 NAE- N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE- N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues.
METHODS
The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis.
RESULTS
The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes.
CONCLUSION
The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.
Topics: Animals; Male; Ethanolamines; Oxidative Stress; Rats, Sprague-Dawley; Aging; Myocardium; Stearic Acids; Antioxidants; Age Factors; Nitrosative Stress; Inflammation Mediators; Cardiotonic Agents; Rats
PubMed: 38279735
DOI: 10.2174/0118746098275323231226073348