-
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 -
Journal of Dairy Science Jun 2024The nutritional components and quality of milk are influenced by the rumen microbiota and its metabolites at different lactation stages. Hence, rumen fluid and milk...
Multiomics analysis revealed that the metabolite profile of raw milk is associated with lactation stage of dairy cows and could be affected by variations in the ruminal microbiota.
The nutritional components and quality of milk are influenced by the rumen microbiota and its metabolites at different lactation stages. Hence, rumen fluid and milk samples from 6 dairy cows fed the same diet were collected during peak, early mid- and later mid-lactation. Untargeted metabolomics and 16S rRNA sequencing were applied for analyzing milk and rumen metabolites, as well as rumen microbial composition, respectively. The levels of lipid-related metabolites, L-glutamate, glucose-1-phosphate and acetylphosphate in milk exhibited lactation-dependent attenuation. Maltol, N-acetyl-D-glucosamine, and choline, which are associated with milk flavor or coagulation properties, as well as L-valine, lansioside-A, clitocine and ginsenoside-La increased significantly in early mid- and later mid-lactation, especially in later mid-lactation. The obvious increase in rumen microbial diversities (Ace and Shannon indices) were observed in early mid-lactation compared with peak lactation. Twenty-one differential bacterial genera of the rumen were identified, with Succinivibrionaceae_UCG-001, Candidatus Saccharimonas, Fibrobacter, and SP3-e08 being significantly enriched in peak lactation. Rikenellaceae_RC9_gut_group, Eubacterium_ruminantium_group, Lachnospira, Butyrivibrio, Eubacterium_hallii_group, and Schwartzia were most significantly enriched in early mid-lactation. In comparison, only 2 bacteria (unclassified_f__Prevotellaceae and Prevotellaceae_UCG-001) were enriched in later mid-lactation. For rumen metabolites, LPE(16:0), L-glutamate and L-tyrosine had higher levels in peak lactation, whereas PE(17:0/0:0), PE(16:0/0:0), PS(18:1(9Z)/0:0), L-phenylalanine, dulcitol, 2-(methoxymethyl)furan and 3-phenylpropyl acetate showed higher levels in early mid- and later mid-lactation. Multiomics integrated analysis revealed that a greater abundance of Fibrobacter contributed to phospholipid content in milk by increasing ruminal acetate, L-glutamate and LysoPE(16:0). Prevotellaceae_UCG-001 and unclassified_f_Prevotellaceae provide substrates for milk metabolites of the same category by increasing ruminal L-phenylalanine and dulcitol contents. These results demonstrated that milk metabolomic fingerprints and critical functional metabolites during lactation, and the key bacteria in rumen related to them. These findings provide new insights into the development of functional dairy products.
PubMed: 38876221
DOI: 10.3168/jds.2024-24753 -
Nutrition Research and Practice Jun 2024Kaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects....
BACKGROUND/OBJECTIVES
Kaempferol (Ka) is one of the most widely occurring flavonoids found in large amounts in various plants. Ka has anti-obesity, antioxidant, and anti-inflammatory effects. Despite the numerous papers documenting the efficacy of Ka, some controversy remains. Therefore, this study examined the impact of Ka using 3T3-L1 and high-fat diet-induced obese mice.
MATERIALS/METHODS
3T3-L1 cells were treated with 50 μM Ka from the initiation of 3T3-L1 differentiation at D0 until the completion of differentiation on D8. Thirty male mice (C57BL/6J, 4 weeks old) were divided into 3 groups: normal diet (ND), high-fat diet (HFD), and HFD + 0.02% (w/w) Ka (Ka) group. All mice were fed their respective diets for 16 weeks. The mice were sacriced, and the plasma and hepatic lipid levels, white adipose tissue weight, hepatic glucose level, lipid level, and antioxidant enzyme activities were analyzed, and immunohistochemistry staining was performed.
RESULTS
Ka suppressed the hypertrophy of 3T3-L1 cells, and the Ka-supplemented mice showed a significant decrease in perirenal, retroperitoneal, mesenteric, and subcutaneous fat compared to the HFD group. Ka supplementation in high-fat diet-induced obese mice also improved the overall blood lipid concentration (total cholesterol, non-high-density lipoprotein-cholesterol, phospholipids, and apolipoprotein B). Ka supplementation in high-fat-induced obesity mice reduced hepatic steatosis and insulin resistance by modulating the hepatic lipid (glucose-6-phosphate dehydrogenase, fatty acid synthase, malic enzyme, phosphatidate phosphohydrolase, and β-oxidation) activities and glucose (glucokinase, phosphoenolpyruvate carboxykinase, and G6pase)-regulating enzymes. Ka supplementation ameliorated the erythrocyte and hepatic mitochondrial HO and inflammation levels (plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interleukin-6, and interferon-gamma and fibrosis of liver and epididymal fat).
CONCLUSION
Ka may be beneficial for preventing diet-induced obesity, inflammation, oxidative stress, and diabetes.
PubMed: 38854471
DOI: 10.4162/nrp.2024.18.3.325 -
Cell Death & Disease Jun 2024Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in...
Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo Apoe and Apoo Ldlr mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.
Topics: Animals; Receptors, LDL; Cholesterol; NF-E2-Related Factor 2; Mice; Mice, Knockout; Mice, Inbred C57BL; Lipid Metabolism; Male; Atherosclerosis; Apolipoproteins; Humans; Liver; Apolipoproteins E; Hyperlipidemias
PubMed: 38830896
DOI: 10.1038/s41419-024-06778-4 -
Journal of Dairy Science May 2024The focus of this work is the role milk polar lipids play in affecting gut permeability, systemic inflammation, and lipid metabolism during acute and chronic...
Dietary milk polar lipids modulate gut barrier integrity and lipid metabolism in C57BL/6J mice during systemic inflammation induced by Escherichia coli lipopolysaccharide.
The focus of this work is the role milk polar lipids play in affecting gut permeability, systemic inflammation, and lipid metabolism during acute and chronic inflammation induced by a single subcutaneous injection of lipopolysaccharide. Three groups of C57BL/6J mice were fed: modified AIN-93G diet with moderate level of fat (CO); CO with milk gangliosides (GG); CO with milk phospholipids (MPL). The MPL did not prevent a gut permeability increase upon LPS stress but increased the expression of tight junction proteins zonula occludens-1 and occludin in colon mucosa. The GG prevented the gut permeability increase upon LPS stress. The MPL decreased absolute and relative liver mass and decreased hepatic gene expression of acetyl-CoA carboxylase 2 and 3-hydroxy-3-methylglutaryl-CoA reductase. The GG increased hepatic gene expression of acetyl-CoA acyltransferase 2. In conclusion, milk GG protected the intestinal barrier integrity but had little effect on systemic inflammation and lipid metabolism; milk MPL, conversely, had complex effects on gut permeability, did not affect systemic inflammation, and had beneficial effect on hepatic lipid metabolism.
PubMed: 38825111
DOI: 10.3168/jds.2024-24759 -
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 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 -
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