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PeerJ 2024As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of...
As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.
Topics: Animals; Non-alcoholic Fatty Liver Disease; Glycerophospholipids; Coumarins; Lipidomics; Mice; Chromatography, Liquid; Male; Disease Models, Animal; Mice, Inbred C57BL; Diet, High-Fat; Mass Spectrometry; Lipid Metabolism
PubMed: 38799063
DOI: 10.7717/peerj.17380 -
Journal of Human Nutrition and... May 2024Milk fat globule membranes (MFGM) present a nutritional intervention with the potential to improve psychological well-being and mitigate the negative effects of stress...
Milk fat globule membranes for psychological and physical health: qualitative results from the Employing Milk Phospholipids to Observe Well-being and Emotional Resilience (EMPOWER) randomised trial.
BACKGROUND
Milk fat globule membranes (MFGM) present a nutritional intervention with the potential to improve psychological well-being and mitigate the negative effects of stress on health. The present study aimed to investigate participant's experience of different aspects of health during a trial of MFGM supplementation and determine the effect of MFGM on qualitative measures of psychological and physical well-being.
METHODS
Seventy-three adults in New Zealand who were enrolled in a clinical trial to test MFGM supplementation for improvement of psychological well-being took part in a post-intervention interview. Participants and researchers remained blinded to intervention group allocation. Interviews were conducted over the video conferencing platform Zoom and transcribed. A mixed methods analytical approach included thematic analysis to identify emerging themes and χ regression models to examine frequency of improvements in different aspects of well-being between the MFGM and placebo groups.
RESULTS
There were no significant demographic or psychological differences between interviewees and non-interviewed study participants. Four central themes emerged from the data for all participants: improved well-being, increased ability to cope with stress and improvements in mood, improvement in physical energy or activity, and improved sleep. The frequency of improved ability to cope with stress and improved sleep quality was significantly higher in participants who received MFGM supplementation compared to those receiving the placebo.
CONCLUSIONS
Qualitative data may capture aspects of improved sleep or psychological well-being not measured by rating scales. The results suggest that MFGM supplementation may improve the ability to cope with stress and improve sleep quality in healthy adults.
PubMed: 38798237
DOI: 10.1111/jhn.13326 -
Journal of Oleo Science Jun 2024Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary...
Similar Distribution between EPA-containing Phosphatidylcholine and Mesenchymal Stem Marker Positive Cells in the Aortic Wall of Abdominal Aortic Aneurysm Model Rat Fed a Low-EPA Content Diet.
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary components are closely associated with AAA. Among those dietary components, eicosapentaenoic acid (EPA) is considered to have suppressive effects on AAA. In the AAA wall of AAA model animals bred under EPA-rich condition, the distribution of EPA-containing phosphatidylcholine (EPA-PC) has been reported to be similar to that of the markers of mesenchymal stem cells (MSCs) and M2 macrophages. These data suggest that the suppressive effects of EPA on AAA are related to preferential distribution of specific cells in the aortic wall. However, the distribution of EPA-PC in the AAA wall of AAA model animals fed a diet containing small amounts of EPA, which has not been reported to inhibit AAA, has not yet been explored. In the present study, we visualized the distribution of EPA-PCs in the AAA wall of AAA model animals fed a diet containing small amounts of EPA (1.5% EPA in the fatty acid composition) to elucidate the vasoprotective effects of EPA. Positive areas for markers of MSCs were significantly higher in the region where EPA-PC was abundant compared to the regions where EPA-PC was weakly detected, but not for markers of M2 macrophages, matrix metalloproteinase (MMP)-2, and MMP-9. The distribution of MSC markers was similar to that of EPA-PC but not that of M2 macrophages and MMPs. These data suggest preferential incorporation of EPA into MSCs under the conditions used in this study. The incorporation of EPA into certain cells may differ according to dietary conditions, which affect the development of AAA.
Topics: Animals; Eicosapentaenoic Acid; Aortic Aneurysm, Abdominal; Mesenchymal Stem Cells; Disease Models, Animal; Phosphatidylcholines; Aorta, Abdominal; Male; Diet; Rats; Macrophages; Biomarkers; Matrix Metalloproteinase 9
PubMed: 38797690
DOI: 10.5650/jos.ess23269 -
Journal of Dairy Science May 2024The fatty acid (FA) and phospholipid composition of dietary lecithin may influence FA digestibility and milk production in cattle. Eight multiparous Holstein cows (99.4...
The fatty acid (FA) and phospholipid composition of dietary lecithin may influence FA digestibility and milk production in cattle. Eight multiparous Holstein cows (99.4 ± 9.2 d in milk [DIM]; 48.9 ± 3.8 kg milk/d) were enrolled in a 3 × 3 incomplete Latin square design with 3 treatments provided as continuous abomasal infusates spanning 14-d experimental periods: water (CON), soybean phospholipids (SOY; 74.5 g of deoiled soy lecithin), or sunflower phospholipids (SUN; 133.5 g of hydrolyzed sunflower lecithin). Cows were fed the same diet, which contained (% dry matter) 27.0% neutral detergent fiber (NDF), 15.6% crude protein (CP), 26.2% starch, and 5.87% FA. Treatments did not modify body weight, milk fat, protein, or lactose contents, or the efficiency of producing energy-corrected milk. Cows infused with SUN had greater milk yields than those receiving SOY or CON treatments. Cows infused with SUN had higher total solids, protein, and lactose yields than cows receiving the SOY or CON treatments. Sunflower phospholipids enhanced feed efficiency (milk yield/dry matter intake) relative to SOY or CON. Treatment did not affect intakes or apparent total-tract digestibilities for NDF, CP, starch, or 16-carbon (16C) FA. Cows receiving SUN had greater total FA and 18-carbon (18C) FA intakes than SOY or CON, but treatments did not impact their digestibility. Milk FA composition was modified by treatment. Cows receiving SUN had a greater concentration of polyunsaturated FA and lower concentrations of saturated FA and monounsaturated FA in milk relative to SOY or CON. In conclusion, the abomasal infusion of SUN improved milk production and milk FA composition, indicating potential benefits for dairy cow nutrition and milk quality.
PubMed: 38788840
DOI: 10.3168/jds.2023-24369 -
Food & Function Jun 2024Phospholipids are the essential components of human milk, contributing to the enhancement of cognitive development, regulation of immune functions, and mitigation of... (Review)
Review
Phospholipids are the essential components of human milk, contributing to the enhancement of cognitive development, regulation of immune functions, and mitigation of elevated cholesterol levels. Infant formulas supplemented with phospholipids can change the composition, content, and globule membrane structure of milk lipids, improving their digestive properties and nutritional value. However, mimicking phospholipids in infant formulas is currently limited, and the supplemented standards of phospholipid species and amounts in infant formulas are unknown. Consequently, there is a significant difference between the phospholipids in infant formulas and those in human milk. This article reviews the recent progress in human milk phospholipid research, aiming to describe the composition, content, and positive effects of human milk phospholipids, as well as summarises the dietary sources of phospholipid supplementation and the current state of human milk phospholipid mimicking in infant formulas. This review provides clear directions for research on mimicking human milk phospholipids and evaluating the nutritional functions of phospholipids in infants.
Topics: Humans; Milk, Human; Phospholipids; Infant Formula; Infant; Nutritive Value; Infant Nutritional Physiological Phenomena; Infant, Newborn; Dietary Supplements
PubMed: 38787648
DOI: 10.1039/d4fo00539b -
FASEB Journal : Official Publication of... May 2024Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects....
Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. In vivo, ApoE mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. In vitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.
Topics: Animals; Ferroptosis; NF-E2-Related Factor 2; Melatonin; Mice; Atherosclerosis; Male; Amino Acid Transport System y+; Diet, High-Fat; Macrophages; Mice, Inbred C57BL; Phospholipid Hydroperoxide Glutathione Peroxidase; Oxidative Stress; Signal Transduction; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Lipoproteins, LDL; Antioxidants
PubMed: 38780199
DOI: 10.1096/fj.202400427RR -
Journal of Agricultural and Food... Jun 2024Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or... (Review)
Review
Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.
Topics: NF-E2-Related Factor 2; Polyphenols; Humans; Lipid Peroxidation; Phospholipid Hydroperoxide Glutathione Peroxidase; Animals; Signal Transduction; Plant Extracts; Antioxidants; Oxidative Stress; Membrane Lipids; Reactive Oxygen Species
PubMed: 38776233
DOI: 10.1021/acs.jafc.4c00523 -
Hepatology (Baltimore, Md.) May 2024The common genetic variant rs641738 C>T is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated...
BACKGROUND AND AIMS
The common genetic variant rs641738 C>T is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), including liver fibrosis, and is associated with decreased expression of the phospholipid-remodeling enzyme MBOAT7 (LPIAT1). However, whether restoring MBOAT7 expression in established MASLD dampens the progression to liver fibrosis and, importantly, the mechanism through which decreased MBOAT7 expression exacerbates MASH fibrosis remain unclear.
APPROACH AND RESULTS
We first showed that hepatocyte MBOAT7 restoration in mice with diet-induced steatohepatitis slows the progression to liver fibrosis. Conversely, when hepatocyte-MBOAT7 was silenced in mice with established hepatosteatosis, liver fibrosis but not hepatosteatosis was exacerbated. Mechanistic studies revealed that hepatocyte-MBOAT7 restoration in MASH mice lowered hepatocyte-TAZ (WWTR1), which is known to promote MASH fibrosis. Conversely, hepatocyte-MBOAT7 silencing enhanced TAZ upregulation in MASH. Finally, we discovered that changes in hepatocyte phospholipids due to MBOAT7 loss-of-function promote a cholesterol trafficking pathway that upregulates TAZ and the TAZ-induced profibrotic factor Indian hedgehog (IHH). As evidence for relevance in humans, we found that the livers of individuals with MASH carrying the rs641738-T allele had higher hepatocyte nuclear TAZ, indicating higher TAZ activity, and increased IHH mRNA.
CONCLUSIONS
This study provides evidence for a novel mechanism linking MBOAT7-LoF to MASH fibrosis; adds new insight into an established genetic locus for MASH; and, given the druggability of hepatocyte TAZ for MASH fibrosis, suggests a personalized medicine approach for subjects at increased risk for MASH fibrosis due to inheritance of variants that lower MBOAT7.
PubMed: 38776184
DOI: 10.1097/HEP.0000000000000933 -
Clinical and Experimental Hepatology Dec 2023We aimed to examine the influence of N-acetylcysteine (NAC) on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) in rats with a...
AIM OF THE STUDY
We aimed to examine the influence of N-acetylcysteine (NAC) on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) in rats with a specific focus on the eicosanoid pathway.
MATERIAL AND METHODS
The experiment was conducted on male Wistar rats fed a standard diet or a high-fat diet (HFD) for eight weeks. In the entire experiment, half of rats from both groups received intragastrically NAC solution prepared in normal saline. H + E staining was used for the histological assessment of liver tissue. The gas-liquid chromatography (GLC) technique was used for the assessment of the activity of n-3 and n-6 polyunsaturated fatty acid (PUFA) pathways and arachidonic acid concentration. ELISA and multiplex immunoassay kits were applied for the measurement of eicosanoid, cytokine, and chemokine levels. The Western blot technique was applied to determine the expression of proteins involved in the inflammation pathway.
RESULTS
NAC decreased hepatic n-6 PUFA activity in all examined lipid pools and decreased the hepatic content of arachidonic acid as a pro-inflammatory precursor in each lipid pool, especially in the phospholipid fraction in rats with fatty lipid disease. NAC administration abolished 5-LOX expression, leading to a decrease in the content of pro-inflammatory leukotriene B4 and leukotriene C4. In rats with steatosis, NAC weakened NF-κB expression and raised Nrf-2 expression, inhibiting the synthesis of pro-inflammatory cytokines and chemokines.
CONCLUSIONS
NAC treatment significantly rate-limited the progression of simple hepatic steatosis to hepatitis in a rat model of MASLD.
PubMed: 38774197
DOI: 10.5114/ceh.2023.133106 -
Communications Biology May 2024Glycerophosphocholine (GPC) is an important precursor for intracellular choline supply in phosphatidylcholine (PC) metabolism. GDE5/Gpcpd1 hydrolyzes GPC into choline...
Glycerophosphocholine (GPC) is an important precursor for intracellular choline supply in phosphatidylcholine (PC) metabolism. GDE5/Gpcpd1 hydrolyzes GPC into choline and glycerol 3-phosphate; this study aimed to elucidate its physiological function in vivo. Heterozygous whole-body GDE5-deficient mice reveal a significant GPC accumulation across tissues, while homozygous whole-body knockout results in embryonic lethality. Skeletal muscle-specific GDE5 deletion (Gde5 skKO) exhibits reduced passive force and improved fatigue resistance in electrically stimulated gastrocnemius muscles in vivo. GDE5 deficiency also results in higher glycolytic metabolites and glycogen levels, and glycerophospholipids alteration, including reduced levels of phospholipids that bind polyunsaturated fatty acids (PUFAs), such as DHA. Interestingly, this PC fatty acid compositional change is similar to that observed in skeletal muscles of denervated and Duchenne muscular dystrophy mouse models. These are accompanied by decrease of GDE5 expression, suggesting a regulatory role of GDE5 activity for glycerophospholipid profiles. Furthermore, a DHA-rich diet enhances contractile force and lowers fatigue resistance, suggesting a functional relationship between PC fatty acid composition and muscle function. Finally, skinned fiber experiments show that GDE5 loss increases the probability of the ryanodine receptor opening and lowers the maximum Ca-activated force. Collectively, GDE5 activity plays roles in PC and glucose/glycogen metabolism in skeletal muscle.
Topics: Animals; Muscle, Skeletal; Mice; Phosphatidylcholines; Mice, Knockout; Muscle Contraction; Male; Mice, Inbred C57BL; Phosphoric Diester Hydrolases
PubMed: 38769369
DOI: 10.1038/s42003-024-06298-z