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Nutrients Jul 2023Full-fat dairy milk may protect against cardiometabolic disorders, due to the milk fat globule membrane (MFGM), through anti-inflammatory and gut-health-promoting... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
Milk-Fat-Globule-Membrane-Enriched Dairy Milk Compared with a Soy-Lecithin-Enriched Beverage Did Not Adversely Affect Endotoxemia or Biomarkers of Gut Barrier Function and Cardiometabolic Risk in Adults with Metabolic Syndrome: A Randomized Controlled Crossover Trial.
Full-fat dairy milk may protect against cardiometabolic disorders, due to the milk fat globule membrane (MFGM), through anti-inflammatory and gut-health-promoting activities. We hypothesized that a MFGM-enriched milk beverage (MEB) would alleviate metabolic endotoxemia in metabolic syndrome (MetS) persons by improving gut barrier function and glucose tolerance. In a randomized crossover trial, MetS persons consumed for two-week period a controlled diet with MEB (2.3 g/d milk phospholipids) or a comparator beverage (COMP) formulated with soy phospholipid and palm/coconut oil. They then provided fasting blood and completed a high-fat/high-carbohydrate test meal challenge for evaluating postprandial metabolism and intestinal permeability. Participants had no adverse effects and achieved high compliance, and there were no between-trial differences in dietary intakes. Compared with COMP, fasting endotoxin, glucose, incretins, and triglyceride were unaffected by MEB. The meal challenge increased postprandial endotoxin, triglyceride, and incretins, but were unaffected by MEB. Insulin sensitivity; fecal calprotectin, myeloperoxidase, and short-chain fatty acids; and small intestinal and colonic permeability were also unaffected by MEB. This short-term study demonstrates that controlled administration of MEB in MetS persons does not affect gut barrier function, glucose tolerance, and other cardiometabolic health biomarkers, which contradicts observational evidence that full-fat milk heightens cardiometabolic risk. Registered at ClinicalTrials.gov (NCT03860584).
Topics: Adult; Humans; Animals; Metabolic Syndrome; Lecithins; Endotoxemia; Incretins; Cross-Over Studies; Triglycerides; Milk; Phospholipids; Biomarkers; Endotoxins; Glucose; Cardiovascular Diseases
PubMed: 37513677
DOI: 10.3390/nu15143259 -
Hepatology (Baltimore, Md.) Apr 2017Nonalcoholic fatty liver disease (NAFLD) can progress from simple steatosis (i.e., nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH), cirrhosis,... (Comparative Study)
Comparative Study
UNLABELLED
Nonalcoholic fatty liver disease (NAFLD) can progress from simple steatosis (i.e., nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Currently, the driver for this progression is not fully understood; in particular, it is not known how NAFLD and its early progression affects the distribution of lipids in the liver, producing lipotoxicity and inflammation. In this study, we used dietary and genetic mouse models of NAFL and NASH and translated the results to humans by correlating the spatial distribution of lipids in liver tissue with disease progression using advanced mass spectrometry imaging technology. We identified several lipids with distinct zonal distributions in control and NAFL samples and observed partial to complete loss of lipid zonation in NASH. In addition, we found increased hepatic expression of genes associated with remodeling the phospholipid membrane, release of arachidonic acid (AA) from the membrane, and production of eicosanoid species that promote inflammation and cell injury. The results of our immunohistochemistry analyses suggest that the zonal location of remodeling enzyme LPCAT2 plays a role in the change in spatial distribution for AA-containing lipids. This results in a cycle of AA-enrichment in pericentral hepatocytes, membrane release of AA, and generation of proinflammatory eicosanoids and may account for increased oxidative damage in pericentral regions in NASH.
CONCLUSION
NAFLD is associated not only with lipid enrichment, but also with zonal changes of specific lipids and their associated metabolic pathways. This may play a role in the heterogeneous development of NAFLD. (Hepatology 2017;65:1165-1180).
Topics: Animals; Biopsy, Needle; Diet, High-Fat; Diet, Western; Disease Models, Animal; Eicosanoids; Fatty Liver; Humans; Immunohistochemistry; Liver Cirrhosis; Liver Neoplasms; Liver Regeneration; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phospholipids; Prognosis; Random Allocation; Risk Assessment; Severity of Illness Index; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 27863448
DOI: 10.1002/hep.28953 -
Nutrients Jan 2022The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated...
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Diet; Dietary Fats; Docosahexaenoic Acids; Female; Guinea Pigs; Linoleic Acid; Maternal Nutritional Physiological Phenomena; Phospholipids; Pregnancy; Retina; alpha-Linolenic Acid
PubMed: 35057481
DOI: 10.3390/nu14020301 -
Journal of Dairy Science Jan 2023Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species... (Review)
Review
Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.
Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.
Topics: Animals; Humans; Dairy Products; Diabetes Mellitus, Type 2; Diet; Liver; Lysophosphatidylcholines; Milk; Models, Animal; Phosphatidylcholines; Students; Yogurt
PubMed: 36400621
DOI: 10.3168/jds.2022-21938 -
The Journal of Clinical Investigation Oct 2014Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/phosphatidylcholine and L-carnitine, participate in... (Review)
Review
Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/phosphatidylcholine and L-carnitine, participate in the development of atherosclerotic heart disease. A meta-organismal pathway was elucidated involving gut microbiota-dependent formation of TMA and host hepatic flavin monooxygenase 3-dependent (FMO3-dependent) formation of TMA-N-oxide (TMAO), a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks. Collectively, these studies reveal that nutrient precursors, gut microbiota, and host participants along the meta-organismal pathway elucidated may serve as new targets for the prevention and treatment of CVD.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Carnitine; Choline; Diet; Female; Food; Humans; Intestines; Male; Methylamines; Microbiota; Oxygenases; Phosphatidylcholines
PubMed: 25271725
DOI: 10.1172/JCI72331 -
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 -
European Journal of Pharmaceutics and... Aug 2020The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug's solubility in human intestinal fluid (HIF), a...
The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug's solubility in human intestinal fluid (HIF), a key factor that influences bioavailability and biopharmaceutical classification. However, HIF is difficult to obtain and is known to be variable, which has led to the development of a range of simulated intestinal fluid (SIF) systems to determine drug solubility in vitro. In this study we have applied a novel multidimensional approach to analyse and characterise HIF composition using a published data set in both fasted and fed states with a view to refining the existing SIF approaches. The data set provided 152 and 172 measurements of five variables (total bile salt, phospholipid, total free fatty acid, cholesterol and pH) in time-dependent HIF samples from 20 volunteers in the fasted and fed state, respectively. The variable data sets for both fasted state and fed state are complex, do not follow normal distributions but the amphiphilic variable concentrations are correlated. When plotted 2-dimensionally a generally ellipsoid shaped data cloud with a positive slope is revealed with boundaries that enclose published fasted or fed HIF compositions. The data cloud also encloses the majority of fasted state and fed state SIF recipes and illustrates that the structured nature of design of experiment (DoE) approaches does not optimally cover the variable space and may examine media compositions that are not biorelevant. A principal component analysis in either fasted or fed state in combination with fitting an ellipsoid shape to enclose the data results in 8 points that capture over 95% of the compositional variability of HIF. The variable's average rate of concentration change in both fasted state and fed state over a short time scale (10 min) is zero and a Euclidean analysis highlights differences between the fasted and fed states and among individual volunteers. The results indicate that a 9-point DoE (8 + 1 central point) could be applied to investigate drug solubility in vitro and provide statistical solubility limits. In addition, a single point could provide a worst-case solubility measurement to define the lowest biopharmaceutical classification boundary or for use during drug development. This study has provided a novel description of HIF composition. The approach could be expanded in multiple ways by incorporation of further data sets to improve the statistical coverage or to cover specific patient groups (e.g., paediatric). Further development might also be possible to analyse information on the time dependent behaviour of HIF and to guide HIF sampling and analysis protocols.
Topics: Administration, Oral; Body Fluids; Fasting; Humans; Intestinal Absorption; Intestinal Secretions; Intestines; Pharmaceutical Preparations; Phospholipids; Solubility
PubMed: 32585351
DOI: 10.1016/j.ejpb.2020.06.011 -
International Journal of Molecular... Jan 2017Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years,... (Review)
Review
Milk is one of the most important foods for mammals, because it is the first form of feed providing energy, nutrients and immunological factors. In the last few years, milk lipids have attracted the attention of researchers due to the presence of several bioactive components in the lipid fraction. The lipid fraction of milk and dairy products contains several components of nutritional significance, such as ω-3 and ω-6 polyunsaturated fatty acids, CLA, short chain fatty acids, gangliosides and phospholipids. Prospective cohort evidence has shown that phospholipids play an important role in the human diet and reinforce the possible relationship between their consumption and prevention of several chronic diseases. Because of these potential benefits of phospholipids in the human diet, this review is focused on the recent advances in phospholipids from colostrum, milk and dairy by-products. Phospholipid composition, its main determination methods and the health activities of these compounds will be addressed.
Topics: Animals; Colostrum; Dairy Products; Diet; Humans; Inflammation; Milk; Neoplasms; Nervous System Diseases; Phospholipids
PubMed: 28106745
DOI: 10.3390/ijms18010173 -
Adipocyte Dec 2022Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to...
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways.
Topics: Animals; Biological Phenomena; Diet, High-Fat; Fatty Liver; Humans; Inflammation; Lysophospholipids; Mice; Mice, Inbred C57BL; Obesity; Sphingosine; Sphingosine-1-Phosphate Receptors
PubMed: 35094654
DOI: 10.1080/21623945.2021.2021700 -
The Journal of Nutritional Biochemistry Feb 2023Squalene is a key minor component of virgin olive oil, the main source of fat in the Mediterranean diet, and had shown to improve the liver metabolism in rabbits and...
Dietary squalene supplementation decreases triglyceride species and modifies phospholipid lipidomic profile in the liver of a porcine model of non-alcoholic steatohepatitis.
Squalene is a key minor component of virgin olive oil, the main source of fat in the Mediterranean diet, and had shown to improve the liver metabolism in rabbits and mice. The present research was carried out to find out whether this effect was conserved in a porcine model of hepatic steatohepatitis and to search for the lipidomic changes involved. The current study revealed that a 0.5% squalene supplementation to a steatotic diet for a month led to hepatic accumulation of squalene and decreased triglyceride content as well as area of hepatic lipid droplets without influencing cholesterol content or fiber areas. However, ballooning score was increased and associated with the hepatic squalene content. Of forty hepatic transcripts related to lipid metabolism and hepatic steatosis, only citrate synthase and a non-coding RNA showed decreased expressions. The hepatic lipidome, assessed by liquid chromatography-mass spectrometry in a platform able to analyze 467 lipids, revealed that squalene supplementation increased ceramide, Cer(36:2), and phosphatidylcholine (PC[32:0], PC[33:0] and PC[34:0]) species and decreased cardiolipin, CL(69:5), and triglyceride (TG[54:2], TG[55:0] and TG[55:2]) species. Plasma levels of interleukin 12p40 increased in pigs receiving the squalene diet. The latter also modified plasma lipidome by increasing TG(58:12) and decreasing non-esterified fatty acid (FA 14:0, FA 16:1 and FA 18:0) species without changes in total NEFA levels. Together this shows that squalene-induced changes in hepatic and plasma lipidomic profiles, non-coding RNA and anti-inflammatory interleukin are suggestive of an alleviation of the disease despite the increase in the ballooning score.
Topics: Swine; Mice; Animals; Rabbits; Squalene; Lipidomics; Triglycerides; Phospholipids; Diet, High-Fat; Liver; Non-alcoholic Fatty Liver Disease; Dietary Supplements; RNA, Untranslated
PubMed: 36402249
DOI: 10.1016/j.jnutbio.2022.109207