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Journal of the American Society For... Jun 2024Bone fracture healing is a complex process in which specific molecular knowledge is still lacking. The citrulline-arginine-nitric oxide metabolism is one of the involved...
Bone fracture healing is a complex process in which specific molecular knowledge is still lacking. The citrulline-arginine-nitric oxide metabolism is one of the involved pathways, and its enrichment via citrulline supplementation can enhance fracture healing. This study investigated the molecular effects of citrulline supplementation during the different fracture healing phases in a rat model. Microcomputed tomography (μCT) was applied for the analysis of the fracture callus formation. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid-chromatography tandem mass spectrometry (LC-MS/MS) were used for lipid and protein analyses, respectively. μCT analysis showed no significant differences in the fracture callus volume and volume fraction between the citrulline supplementation and control group. The observed lipid profiles for the citrulline supplementation and control group were distinct for the different fracture healing stages. The main contributing lipid classes were phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs). The changing effect of citrulline supplementation throughout fracture healing was indicated by changes in the differentially expressed proteins between the groups. Pathway analysis showed an enhancement of fracture healing in the citrulline supplementation group in comparison to the control group via improved angiogenesis and earlier formation of the soft and hard callus. This study showed the molecular effects on lipids, proteins, and pathways associated with citrulline supplementation during bone fracture healing, even though no effect was visible with μCT.
Topics: Animals; Fracture Healing; Rats; Citrulline; Rats, Sprague-Dawley; Tandem Mass Spectrometry; X-Ray Microtomography; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Dietary Supplements; Disease Models, Animal; Male; Bony Callus; Chromatography, Liquid; Lysophosphatidylcholines; Phosphatidylcholines
PubMed: 38679918
DOI: 10.1021/jasms.4c00028 -
Journal of Ethnopharmacology Sep 2024Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic,...
ETHNOPHARMACOLOGICAL RELEVANCE
Plantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field.
AIM
This study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models.
METHODS
The main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined.
RESULTS
A total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV).
CONCLUSION
Our results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.
Topics: Animals; Diabetic Nephropathies; Male; Sphingosine; Lysophospholipids; Mice; Diabetes Mellitus, Experimental; Plant Extracts; Mice, Inbred C57BL; Phosphotransferases (Alcohol Group Acceptor); Signal Transduction; Kidney
PubMed: 38677576
DOI: 10.1016/j.jep.2024.118221 -
Nutrients Apr 2024We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period...
We aimed to investigate the associations between maternal intake of folate, vitamin B12, B6, B2, methionine, choline, phosphatidylcholine and betaine during the period surrounding pregnancy and offspring weight outcomes from birth to early adulthood. These associations were examined among 2454 mother-child pairs from the Nurses' Health Study II and Growing Up Today Study. Maternal energy-adjusted nutrient intakes were derived from food frequency questionnaires. Birth weight, body size at age 5 and repeated BMI measurements were considered. Overweight/obesity was defined according to the International Obesity Task Force (<18 years) and World Health Organization guidelines (18+ years). Among other estimands, we report relative risks (RRs) for offspring ever being overweight with corresponding 95% confidence intervals across quintiles of dietary factors, with the lowest quintile as the reference. In multivariate-adjusted models, higher maternal intakes of phosphatidylcholine were associated with a higher risk of offspring ever being overweight (RRQ5vsQ1 = 1.16 [1.01-1.33] -trend: 0.003). The association was stronger among offspring born to mothers with high red meat intake (high red meat RRQ5vsQ1 = 1.50 [1.14-1.98], -trend: 0.001; low red meat RRQ5vsQ1 = 1.05 [0.87-1.27], -trend: 0.46; -interaction = 0.13). Future studies confirming the association between a higher maternal phosphatidylcholine intake during pregnancy and offspring risk of being overweight or obese are needed.
Topics: Humans; Female; Pregnancy; Prospective Studies; Adult; Maternal Nutritional Physiological Phenomena; Overweight; Diet; Risk Factors; Male; Obesity; Child, Preschool; Body Mass Index; Choline; Phosphatidylcholines; Prenatal Exposure Delayed Effects; Birth Weight
PubMed: 38674900
DOI: 10.3390/nu16081210 -
International Journal of Molecular... Apr 2024Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate...
Atopic dermatitis (AD), a chronic inflammatory skin disease, is exacerbated by obesity, yet the precise linking mechanism remains elusive. This study aimed to elucidate how obesity amplifies AD symptoms. We studied skin samples from three mouse groups: sham control, AD, and high-fat (HF) + AD. The HF + AD mice exhibited more severe AD symptoms than the AD or sham control mice. Skin lipidome analysis revealed noteworthy changes in arachidonic acid (AA) metabolism, including increased expression of , a key enzyme in AA generation. Genes for phospholipid transport () and acyltransferase utilizing AA as the acyl donor () were upregulated in HF + AD skin. Associations were observed between AA-containing phospholipids and skin lipids containing AA and its metabolites. Furthermore, imbalanced phospholipid metabolism was identified in the HF + AD mice, marked by excessive activation of the AA and phosphatidic acid (PA)-mediated pathway. This imbalance featured increased expression of , , and involved in PA generation, along with a decrease in genes converting PA into diglycerol (DG) and CDP-DG ( and ). This investigation revealed imbalanced phospholipid metabolism in the skin of HF + AD mice, contributing to the heightened inflammatory response observed in HF + AD, shedding light on potential mechanisms linking obesity to the exacerbation of AD symptoms.
Topics: Animals; Dermatitis, Atopic; Obesity; Mice; Diet, High-Fat; Disease Models, Animal; Skin; Lipid Metabolism; Mice, Inbred C57BL; Arachidonic Acid; Lipidomics; Male; Phospholipids
PubMed: 38673730
DOI: 10.3390/ijms25084143 -
Metabolites Mar 2024Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported...
Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention ( < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET ( < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.
PubMed: 38668319
DOI: 10.3390/metabo14040191 -
Respiratory Investigation Jul 2024Recent advances in fatty acid analysis have highlighted the links between lipid disruption and disease development. Lipid abnormalities are well-established risk factors... (Review)
Review
Recent advances in fatty acid analysis have highlighted the links between lipid disruption and disease development. Lipid abnormalities are well-established risk factors for many of the most common chronic illnesses, and their involvement in asthma is also becoming clear. Here, we review research demonstrating the role of abnormal lipid metabolism in asthma, with a focus on saturated fatty acids and sphingolipids. High levels of palmitic acid, the most abundant saturated fatty acid in the human body, have been found in the airways of asthmatic patients with obesity, and were shown to worsen eosinophilic airway inflammation in asthma model mice on a high-fat diet. Aside from being a building block of longer-chain fatty acids, palmitic acid is also the starting point for de novo synthesis of ceramides, a class of sphingolipids. We outline the three main pathways for the synthesis of ceramides, which have been linked to the severity of asthma and act as precursors for the dynamic lipid mediator sphingosine 1-phosphate (S1P). S1P signaling is involved in allergen-induced eosinophilic inflammation, airway hyperresponsiveness, and immune-cell trafficking. A recent study of mice with mutations for the elongation of very long-chain fatty acid family member 6 (Elovl6), an enzyme that elongates fatty acid chains, has highlighted the potential role of palmitic acid composition, and thus lipid balance, in the pathophysiology of allergic airway inflammation. Elovl6 may be a potential therapeutic target in severe asthma.
Topics: Asthma; Humans; Animals; Sphingolipids; Ceramides; Mice; Lipid Metabolism; Fatty Acids; Palmitic Acid; Fatty Acid Elongases; Lysophospholipids; Sphingosine; Acetyltransferases; Disease Models, Animal; Obesity; Signal Transduction; Diet, High-Fat
PubMed: 38640569
DOI: 10.1016/j.resinv.2024.04.006 -
Molecular Nutrition & Food Research May 2024The intestinal immune system plays a crucial role in obesity and insulin resistance. An altered intestinal immunity is associated with changes to the gut microbiota,... (Review)
Review
The intestinal immune system plays a crucial role in obesity and insulin resistance. An altered intestinal immunity is associated with changes to the gut microbiota, barrier function, and tolerance to luminal antigens. Lipid metabolism and its unbalance can also contribute to acute and chronic inflammation in different conditions. In celiac disease (CD), the serum phospholipid profile in infants who developed CD is dramatically different when compared to that of infants at risk of CD not developing the disease. In a mouse model of gluten sensitivity, oral wheat gliadin challenge in connection with inhibition of the metabolism of arachidonic acid, an omega-6 polyunsaturated fatty acid, specifically induces the enteropathy. Recent evidence suggests that gluten may play a role also for development of life-style related diseases in populations on a high fat diet (HFD). However, the mechanisms behind these effects are not yet understood. Exploratory studies in mice feed HFD show that wheat gliadin consumption affects glucose and lipid metabolic homeostasis, alters the gut microbiota, and the immune cell profile in liver.
Topics: Celiac Disease; Gliadin; Animals; Diet, High-Fat; Obesity; Humans; Gastrointestinal Microbiome; Triticum; Mice; Lipid Metabolism
PubMed: 38632845
DOI: 10.1002/mnfr.202300779 -
Journal of Agricultural and Food... May 2024The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear....
The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; < 0.05), triglycerides (increased by 38.9 mmol/mg prot; < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.
Topics: Animals; Diet, High-Fat; Mice; Sea Cucumbers; Liver; Male; Lipid Metabolism; Plasmalogens; Mice, Inbred C57BL; Triglycerides; Humans; Lipids
PubMed: 38630981
DOI: 10.1021/acs.jafc.4c00152 -
BioEssays : News and Reviews in... Jun 2024Dietary methionine restriction (MR) is associated with a spectrum of health-promoting benefits. Being conducive to prevention of chronic diseases and extension of life... (Review)
Review
Dietary methionine restriction (MR) is associated with a spectrum of health-promoting benefits. Being conducive to prevention of chronic diseases and extension of life span, MR can activate integrated responses at metabolic, transcriptional, and physiological levels. However, how the mitochondria of MR influence metabolic phenotypes remains elusive. Here, we provide a summary of cellular functions of methionine metabolism and an overview of the current understanding of effector mechanisms of MR, with a focus on the aspect of mitochondria-mediated responses. We propose that mitochondria can sense and respond to MR through a modulatory role of lipoylation, a mitochondrial protein modification sensitized by MR.
Topics: Methionine; Mitochondria; Humans; Animals; Lipoylation; Mitochondrial Proteins; Adaptation, Physiological
PubMed: 38616332
DOI: 10.1002/bies.202300218 -
The Journal of Nutrition Jun 2024Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM).
OBJECTIVE
The objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources.
METHODS
In this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed.
RESULTS
Total SM concentrations (∼42 μmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups.
CONCLUSIONS
The higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392.
Topics: Humans; Infant Formula; Animals; Carnitine; Goats; Milk, Human; Infant; Sphingomyelins; Milk; Female; Male; Cattle; Breast Feeding; Esters; Infant, Newborn; Plant Oils
PubMed: 38615734
DOI: 10.1016/j.tjnut.2024.04.020