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Food Chemistry Jun 2024Diacylglycerol (DAG) has garnered attention for its safe and nutritious qualities, and its utilization in emulsion systems to encapsulate hydrophobic bioactives is...
Diacylglycerol (DAG) has garnered attention for its safe and nutritious qualities, and its utilization in emulsion systems to encapsulate hydrophobic bioactives is anticipated to enhance their bioaccessibility. Thus, this study aimed to evaluate the influence of DAG oil as a carrier on the stability and digestive characteristics of nanostructured lipid carriers (NLCs) containing lycopene (LYC). The results indicated that DAG oil demonstrated superior storage and heating stability in comparison to triacylglycerol (TAG) oil. Furthermore, NLCs formulated with DAG oil exhibited a faster rate of lipolysis (>76.3%) and higher loading capacity (1.48%), resulting in an approximate 11% enhancement in the bioaccessibility of LYC (reaching up to 31.4%). DAG oils show considerable potential for enhancing and prolonging the properties and bioactivity of NLC carriers, thereby boosting bioaccessibility. The incorporation of DAG oil in food systems holds promise for enriching their functionality over traditional TAG oil.
PubMed: 38943966
DOI: 10.1016/j.foodchem.2024.140219 -
Pharmacological Reports : PR Jun 2024Metabotropic glutamate receptors (mGluRs) are part of the G protein-coupled receptors (GPCRs) family. They are coupled to G (group I) or G (groups II and III) proteins,... (Review)
Review
Metabotropic glutamate receptors (mGluRs) are part of the G protein-coupled receptors (GPCRs) family. They are coupled to G (group I) or G (groups II and III) proteins, which result in the generation of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP) or the inhibition of adenylyl cyclase, respectively. mGluRs have been implicated in anxiety, depression, learning, and synaptic plasticity. Similarly, CB1 cannabinoid receptors (CB1Rs), also GPCRs, play roles in cognitive function and mood regulation through G-mediated inhibition of adenylyl cyclase. Both mGluRs and CB1Rs exhibit surface labeling and undergo endocytosis. Given the similar cellular distribution and mechanisms of action, this review complies with fundamental data on the potential interactions and mutual regulation of mGluRs and CB1Rs in the context of depression, anxiety, and cognition, providing pioneering insights into their interplay.
PubMed: 38941064
DOI: 10.1007/s43440-024-00612-6 -
The Science of the Total Environment Jun 2024The present study aims to evaluate the effects of 2-ethylhexyldiphenyl phosphate (EHDPP) on glycolipid metabolism in vivo. Adult male zebrafish were exposed to various...
The present study aims to evaluate the effects of 2-ethylhexyldiphenyl phosphate (EHDPP) on glycolipid metabolism in vivo. Adult male zebrafish were exposed to various concentrations (0, 1, 10, 100 and 250 μg/L) of EHDPP for 28 days, and changes in lipid and glucose levels were measured. Results indicated significant liver damages in the 100 and 250 μg/L EHDPP groups, which both exhibited significant decreases in hepatic somatic index (HSI), elevated activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and liver, as well as hepatocyte vacuolation and nuclear pyknosis. Exposure to 100 and 250 μg/L EHDPP led to significant reductions in serum and liver cholesterol (TC), triglycerides (TGs), and lipid droplet deposition, indicating a significant inhibition of EHDPP on hepatic lipid accumulation. Lipidomic analyses manifested that 250 μg/L EHDPP reduced the levels of 103 lipid metabolites which belong to glycerides (TGs, diglycerides, and monoglycerides), fatty acyles (fatty acids), sterol lipids (cholesterol, bile acids), sphingolipids, and glycerophospholipids, and downregulated genes involved in de novo synthesis of fatty acids (fas, acc, srebp1, and dagt2), while upregulated genes involved in fatty acid β-oxidation (pparα and cpt1). KEGG analyses revealed that EHDPP significantly disrupted glycerolipid metabolism, steroid biosynthesis and fatty acid biosynthesis pathways. Collectively, the results showed that EHDPP induced lipid reduction in zebrafish liver, possibly through inhibiting lipid synthesis and disrupting glycerolipid metabolism. Our findings provide a theoretical basis for evaluating the ecological hazards and health effects of EHDPP on glycolipid metabolism.
PubMed: 38936724
DOI: 10.1016/j.scitotenv.2024.174248 -
Life Sciences Jun 2024Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly... (Review)
Review
Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly implicates perirenal adipose tissue (PRAT) deposition as a contributing factor in the pathogenesis of CKD. This review explores how PRAT deposition may exert deleterious effects on renal structure and function. The anatomical proximity of PRAT to the kidneys not only potentially causes mechanical compression but also leads to the dysregulated secretion of adipokines and inflammatory mediators, such as adiponectin, leptin, visfatin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and exosomes. Additionally, PRAT deposition may contribute to renal lipotoxicity through elevated levels of free fatty acids (FFA), triglycerides (TAG), diacylglycerol (DAG), and ceramides (Cer). PRAT deposition is also linked to the hyperactivation of the renin-angiotensin-aldosterone system (RAAS), which further exacerbates CKD progression. Recognizing PRAT deposition as an independent risk factor for CKD underscores the potential of targeting PRAT as a novel strategy for the prevention and management of CKD. This review further discusses interventions that could include measuring PRAT thickness to establish a baseline, managing metabolic risk factors that promote its deposition, and inhibiting key PRAT-induced signaling pathways.
PubMed: 38936605
DOI: 10.1016/j.lfs.2024.122866 -
Allergy Jun 2024Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1...
BACKGROUND
Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII-HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and eCB-related N-acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII-HAE.
METHODS
Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals.
RESULTS
Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls.
CONCLUSIONS
BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets.
PubMed: 38935036
DOI: 10.1111/all.16197 -
Journal of Pediatric Gastroenterology... Jun 2024Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption....
OBJECTIVES
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN.
METHODS
From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life.
RESULTS
All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN.
CONCLUSIONS
Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.
PubMed: 38934410
DOI: 10.1002/jpn3.12241 -
Journal of Diabetes and Metabolic... Jun 2024Metabolic syndrome (MetS) comprises a set of risk factors that contribute to the development of chronic and cardiovascular diseases, increasing the mortality rate....
BACKGROUND AND AIMS
Metabolic syndrome (MetS) comprises a set of risk factors that contribute to the development of chronic and cardiovascular diseases, increasing the mortality rate. Altered lipid metabolism is associated with the development of metabolic disorders such as insulin resistance, obesity, atherosclerosis, and metabolic syndrome; however, there is a lack of knowledge about lipids compounds and the lipidic pathways associated with this condition, particularly in the Latin-American population. Innovative approaches, such as lipidomic analysis, facilitate the identification of lipid species related to these risk factors. This study aimed to assess the plasma lipidome in subjects with MetS.
METHODS
This correlation study included healthy adults and adults with MetS. Blood samples were analyzed. The lipidomic profile was determined using an Agilent Technologies 1260 liquid chromatography system coupled to a Q-TOF 6545 quadrupole mass analyzer with electrospray ionization. The main differences were determined between the groups.
RESULTS
The analyses reveal a distinct lipidomic profile between healthy adults and those with MetS, including increased concentrations of most identified glycerolipids -both triglycerides and diglycerides- and decreased levels of ether lipids and sphingolipids, especially sphingomyelins, in MetS subjects. Association between high triglycerides, waist circumference, and most differentially expressed lipids were found.
CONCLUSION
Our results demonstrate dysregulation of lipid metabolism in subjects with Mets, supporting the potential utility of plasma lipidome analysis for a deeper understanding of MetS pathophysiology.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01423-5.
PubMed: 38932852
DOI: 10.1007/s40200-024-01423-5 -
Lipids in Health and Disease Jun 2024Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here,... (Observational Study)
Observational Study
BACKGROUND
Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.
METHODS
From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out.
RESULTS
A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup.
CONCLUSIONS
We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men.
REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.
Topics: Aged; Female; Humans; Male; Middle Aged; Bile Acids and Salts; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Lipidomics; Sex Characteristics; Sex Factors; Tandem Mass Spectrometry; Triglycerides; Cohort Studies
PubMed: 38926753
DOI: 10.1186/s12944-024-02184-z -
Biomedical Chromatography : BMC Jun 2024Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side...
Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.
PubMed: 38922717
DOI: 10.1002/bmc.5937 -
NPJ Parkinson's Disease Jun 2024Identifying biological factors which contribute to the clinical progression of heterogeneous motor and non-motor phenotypes in Parkinson's disease may help to better...
Identifying biological factors which contribute to the clinical progression of heterogeneous motor and non-motor phenotypes in Parkinson's disease may help to better understand the disease process. Several lipid-related genetic risk factors for Parkinson's disease have been identified, and the serum lipid signature of Parkinson's disease patients is significantly distinguishable from controls. However, the extent to which lipid profiles are associated with clinical outcomes remains unclear. Untargeted high-performance liquid chromatography-tandem mass spectrometry identified >900 serum lipids in Parkinson's disease subjects at baseline (n = 122), and the potential for machine learning models using these lipids to predict motor and non-motor clinical scores after 2 years (n = 67) was assessed. Machine learning models performed best when baseline serum lipids were used to predict the 2-year future Unified Parkinson's disease rating scale part three (UPDRS III) and Geriatric Depression Scale scores (both normalised root mean square error = 0.7). Feature analysis of machine learning models indicated that species of lysophosphatidylethanolamine, phosphatidylcholine, platelet-activating factor, sphingomyelin, diacylglycerol and triacylglycerol were top predictors of both motor and non-motor scores. Serum lipids were overall more important predictors of clinical outcomes than subject sex, age and mutation status of the Parkinson's disease risk gene LRRK2. Furthermore, lipids were found to better predict clinical scales than a panel of 27 serum cytokines previously measured in this cohort (The Michael J. Fox Foundation LRRK2 Clinical Cohort Consortium). These results suggest that lipid changes may be associated with clinical phenotypes in Parkinson's disease.
PubMed: 38918434
DOI: 10.1038/s41531-024-00741-y