ABSTRACT
Oxidative modification of low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are important factors determining cardiovascular risk. This study investigated the antioxidant mechanisms and potential protective effect of a hydroethanolic extract of yerba mate (Ilex paraguaiensis; EHEM) on the inâ vitro oxidation of LDL and HDL. EHEM was found to possess ferric reducing power, DPPH free radical scavenging capacity, metal chelating activity, and NO radical scavenging activity. In addition, EHEM reduced the lipoperoxidation induced by α,α'-Azodiisobutyramidine dihydrochloride (AAPH) in HDL and LDL at all tested concentrations. In this study, we demonstrate the antioxidant properties of yerba mate and its phytochemical compounds. These properties may effectively prevent the inâ vitro oxidation of LDL and HDL molecules, a phenomenon linked to the pathogenesis of atherosclerosis.
Subject(s)
Antioxidants , Ilex paraguariensis , Antioxidants/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Ilex paraguariensis/chemistry , Oxidation-Reduction , LipoproteinsABSTRACT
In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase on 23 adolescents aged 12 to 16 years was carried out. Twelve participants were categorized as obese (BMI > 30 kg/m2 and percentile > 95) and 11 as normal-weight (BMI = 20-25 kg/m2, percentile 5-85). Blood samples were collected after a 12-h overnight fast and postprandially after consumption of a standardized breakfast containing olive oil, tomato, bread, orange juice, and skimmed milk. Obese adolescents exhibited elevated triglyceride concentrations in both fasting and postprandial states and higher TG/apo-B48 ratios, indicating larger postprandial triglyceride-rich lipoprotein (TRL) particle size, which suggests impaired clearance. Obese subjects also exhibited higher n-6 PUFA concentrations, potentially linked to increased TRL hydrolysis and the release of pro-inflammatory adipokines. In contrast, TRL from normal-weight individuals showed higher concentrations of oleic acid and DHA (n-3 PUFA), with possible anti-inflammatory effects. The results indicate an interplay involving postprandial TRL metabolism and adipokines within the context of adolescent obesity, pointing to potential cardiovascular implications in the future.
Subject(s)
Fatty Acids, Omega-3 , Pediatric Obesity , Infant , Humans , Adolescent , Adipokines , Bread , LipoproteinsABSTRACT
BACKGROUND: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice. PURPOSE: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice. STUDY DESIGN AND METHODS: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis. RESULTS: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-ß, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/ß, CYP7A1 and ABCG5 in rat hepatocyte. CONCLUSION: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function.
Subject(s)
Atherosclerosis , Azo Compounds , Drugs, Chinese Herbal , Lipoproteins , Male , Mice , Rats , Animals , Liver X Receptors/metabolism , Cholesterol/metabolism , Orphan Nuclear Receptors/genetics , Orphan Nuclear Receptors/metabolism , Orphan Nuclear Receptors/therapeutic use , ATP Binding Cassette Transporter, Subfamily G, Member 5/metabolism , Mice, Inbred C57BL , Liver , Mice, Knockout , Atherosclerosis/drug therapy , Atherosclerosis/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. AIMS: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. RESULTS: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks' experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. CONCLUSION: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.
Subject(s)
Atherosclerosis , Fabaceae , Galactans , Hypercholesterolemia , Hyperlipidemias , Mannans , Plant Gums , Mice , Animals , Hypercholesterolemia/drug therapy , Hypercholesterolemia/etiology , Cholesterol, LDL , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Lipid Metabolism , Hyperlipidemias/drug therapy , Triglycerides/metabolism , Liver , Lipoproteins , Atherosclerosis/drug therapy , Body Weight , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Phytochemicals/metabolismABSTRACT
As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Humans , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Medicine, Chinese Traditional , Atherosclerosis/drug therapy , Lipoproteins , BiomarkersABSTRACT
Dietary supplements augment the nutritional value of everyday food intake and originate from the historical practices of ancient Egyptian (Ebers papyrus), Chinese (Pen Ts'ao by Shen Nung), Indian (Ayurveda), Greek (Hippocrates), and Arabic herbalists. In modern-day medicine, the use of dietary supplements continues to increase in popularity with greater than 50% of the US population reporting taking supplements. To further compound this trend, many patients believe that dietary supplements are equally or more effective than evidence-based therapies for lipoprotein and lipid-lowering. Supplements such as red yeast rice, omega-3 fatty acids, garlic, cinnamon, plant sterols, and turmeric are marketed to and believed by consumers to promote "cholesterol health." However, these supplements are not subjected to the same manufacturing scrutiny by the Food and Drug Administration as pharmaceutical drugs and as such, the exact contents and level of ingredients in each of these may vary. Furthermore, supplements do not have to demonstrate efficacy or safety before being marketed. The holistic approach to lowering atherosclerotic cardiovascular disease risk makes dietary supplements an attractive option to many patients; however, their use should not come at the expense of established therapies with proven benefits. In this narrative review, we provide a historical and evidence-based approach to the use of some dietary supplements in lipoprotein and lipid-lowering and provide a framework for managing patient expectations.
Subject(s)
Dietary Supplements , Fatty Acids, Omega-3 , Humans , Fatty Acids, Omega-3/therapeutic use , Antioxidants , Cholesterol , LipoproteinsABSTRACT
PURPOSE OF REVIEW: Hypertriglyceridaemia (HTG) is a common condition characterised by elevated levels of plasma triglycerides (TG), which are transported in the blood mainly by TG-rich lipoproteins (TRL). Elevated TG levels (150-400 mg/dL) are associated with increased cardiovascular risk. Severe HTG (>880 mg/dL) is associated with a risk of acute pancreatitis only. Randomised clinical trials investigating the clinical benefit of TG-lowering drugs in patients with elevated TG levels have provided conflicting results. RECENT FINDINGS: Elevated TG levels are only one marker of altered lipid/lipoprotein metabolism and indeed reflect altered concentrations of one or more classes or subfractions of TRL, which in turn may have a different association with CV risk. Fibrates, the drugs most commonly used to treat HTG, provide cardiovascular benefits to only a specific subgroup of patients. The lack of clinical benefit from pemafibrate has emphasised the concept that lowering TG levels is not sufficient to reduce the CV risk unless it is accompanied by a reduction in the number of circulating atherogenic lipoproteins, which can be assessed by determining apolipoprotein B levels. Treatment with omega-3 fatty acids was also ineffective in reducing CV risk, with the exception of icosapent ethyl, which, however, appears to have beneficial effects beyond lipids. New drugs are currently being developed that aim to lower TG levels by targeting apolipoprotein C-III or angiopoietin-like-3, both of which are involved in the metabolism of TGs. TG reduction can be achieved by various drugs, but most of them are ineffective in reducing CV risk. The results of outcome studies on new TG-lowering drugs will clarify whether lowering apoB levels is critical to achieve clinical benefit.
Subject(s)
Hyperlipidemias , Hypertriglyceridemia , Pancreatitis , Humans , Acute Disease , Lipoproteins/metabolism , Hypertriglyceridemia/complications , TriglyceridesABSTRACT
Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.
Subject(s)
Lipoproteins , Manganese , Biological Transport , Homeostasis , Lipids , Protein Transport/physiologyABSTRACT
The application of biosolids or treated sewage sludge containing per- and polyfluoroalkyl substances (PFAS) in agricultural lands and the disposal of sludge in landfills pose high risks to humans and the environment. Although PFAS precursors have not been regulated yet, their potential transformation to highly regulated perfluoroalkyl acids (PFAAs) may enable them to serve as a long-term source and make remediation of PFAAs a continuing task. Therefore, treating precursors in sewage sludge is even more, certainly not less, critical than treating or removing PFAAs. In this study, a green surfactant-modified clay sorbent was evaluated for its efficacy in stabilizing two representative PFAA precursors in sludge, e.g., N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA), in comparison with unmodified clay and powdered activated carbon (PAC). Results showed N-EtFOSAA and 6:2 FTSA exhibited distinct adsorption behaviors in the sludge without sorbents due to their different physicochemical properties, such as hydrophobicity and functional groups. Among the three sorbents, the modified clay reduced the water leachability of N-EtFOSAA and 6:2 FTSA by 91.5% and 95.4%, respectively, compared to controls without amendments at the end of the experiment (47 days). Within the same duration, PAC decreased the water leachability of N-EtFOSAA and 6:2 FTSA by 60.6% and 37.3%, respectively. At the same time, the unmodified clay demonstrated a poor stabilization effect and even promoted the leaching of precursors. These findings suggested that the modified clay had the potential for stabilization of precursors, while negatively charged and/or hydrophilic sorbents, such as the unmodified clay, should be avoided in the stabilization process. These results could provide valuable information for developing effective amendments for stabilizing PFAS in sludge or biosolids. Future research should evaluate the long-term effect of the stabilization approach using actual sludge from wastewater treatment facilities.
Subject(s)
Fluorocarbons , Pulmonary Surfactants , Humans , Surface-Active Agents , Sewage , Clay , Biosolids , Lipoproteins , Charcoal , PowdersABSTRACT
Modulation of microglial response could be a target to reduce neuroinflammation associated with Alzheimer's disease. In this study, we propose that lipophilic bioactive molecules present in pomace olive oil (POO), transported in triglyceride-rich lipoproteins (TRLs), are able to modulate microglial high-oleic sunflower oil (HOSO, points) or pomace olive oil (POO, stripes). In order to prove this hypothesis, a randomized crossover postprandial trial was performed in 18 healthy young women. POO was assayed in opposition to high-oleic sunflower oil (HOSO), a common dietary oil which shares with POO an almost identical fatty acid composition but lacks certain biomolecules with recognized antioxidant and anti-inflammatory activities. TRLs were isolated from blood at the baseline and 2 and 4 hours postprandially and used to treat BV-2 cells to assess their ability to modulate the microglial function. We found that the intake of POO leads to the constitution of postprandial TRLs that are able to modulate the inflammatory response in microglia compared to HOSO. TRL-derived POO reduced the release of pro-inflammatory cytokines (tumor necrosis factor-α, and interleukins 1ß and 6) and nitric oxide and downregulated genes codifying for these cytokines and inducible nitric oxide synthase (iNOS) in BV-2 cells. Moreover, the ingestion of POO by healthy women slightly improved glycemic control and TRL clearance throughout the postprandial phase compared to HOSO. In conclusion, we demonstrated that consuming POO results in postprandial TRLs containing lipophilic bioactive compounds capable of regulating the inflammatory response prompted by microglial activation.
Subject(s)
Lipoproteins , Olive Oil , Plant Oils , Female , Humans , Cytokines , Olive Oil/pharmacology , Plant Oils/pharmacology , Postprandial Period/physiology , Sunflower Oil , TriglyceridesABSTRACT
Evidence exists that the gut microbiota contributes to the alterations of lipid metabolism associated with high-fat diet (HFD). Moreover, the gut microbiota has been found to modulate the metabolism and absorption of dietary lipids, thereby affecting the formation of lipoproteins occurring at the intestinal level as well as systemically, though the pathophysiological implication of altered microbiota composition in HFD and its role in the development of atherosclerotic vascular disease (ATVD) remain to be better clarified. Recently, evidence has been collected indicating that supplementation with natural polyphenols and fibres accounts for an improvement of HFD-associated intestinal dysbiosis, thereby leading to improved lipidaemic profile. This study aimed to investigate the protective effect of a bergamot polyphenolic extract (BPE) containing 48% polyphenols enriched with albedo and pulp-derived micronized fibres (BMF) in the gut microbiota of HFD-induced dyslipidaemia. In particular, rats that received an HFD over a period of four consecutive weeks showed a significant increase in plasma cholesterol, triglycerides and plasma glucose compared to a normal-fat diet (NFD) group. This effect was accompanied by body weight increase and alteration of lipoprotein size and concentration, followed by high levels of MDA, a biomarker of lipid peroxidation. Treatment with a combination of BPE plus BMF (50/50%) resulted in a significant reduction in alterations of the metabolic parameters found in HFD-fed rats, an effect associated with increased size of lipoproteins. Furthermore, the effect of BPE plus BMF treatment on metabolic balance and lipoprotein size re-arrangement was associated with reduced gut-derived lipopolysaccharide (LPS) levels, an effect subsequent to improved gut microbiota as expressed by modulation of the Gram-negative bacteria Proteobacteria, as well as Firmicutes and Bacteroidetes. This study suggests that nutraceutical supplementation of HFD-fed rats with BPE and BMP or with their combination product leads to restored gut microbiota, an effect associated with lipoprotein size re-arrangement and better lipidaemic and metabolic profiles.
Subject(s)
Diet, High-Fat , Gastrointestinal Microbiome , Animals , Rats , Diet, High-Fat/adverse effects , Dietary Fats , Lipoproteins , Plant Extracts/pharmacologyABSTRACT
This study investigated the effect of vegetable and fish oils with different n-3 / n-6 PUFAS ratios on the lipoprotein profile and on the development of murine breast cancer 4T1. Female Balb/c mice (6-7 weeks) received diets containing 4.0% fat during seven weeks. On the fourth week, animals were inoculated into the posterior left flank with 2.5 × 106 4T1 cells. Body weight and food intake were registered and the profile serum lipoproteins was determined. Tumor volume, histopathological and immunohistochemical studies, myeloperoxidase and N-acetylglucosaminidase activities, TNF-α, hemoglobin and VEGF levels were analysed. The highest n-3 / n-6 ratio was found in fish oil (15.8:1), followed by linseed (2.4:1), canola (1:2.1) and soybean (1:9.4) oils. Body weight, food and caloric intake, lipoprotein profile, tumor weight, tumor evolution and histopathological analysis were not different. Canola oil increased cell proliferation when compared to soybean oil, and fish oil changed the inflammatory response and increased VEGF in tumors compared to other groups. The type of fatty acid and the high ratio of n-3 / n-6 PUFAs in the diet influenced cell proliferation and inflammation in the tumor differentially, highlighting the increase of neutrophils and VEGF levels in animals fed on fish oil.
Subject(s)
Fatty Acids, Omega-3 , Vascular Endothelial Growth Factor A , Animals , Female , Mice , Plant Oils , Dietary Fats , Fatty Acids, Omega-3/analysis , Fish Oils/metabolism , Fatty Acids/analysis , Lipoproteins , Body WeightABSTRACT
The purification and collection of various products from oil/water mixtures are routine procedures. However, the presence of emulsifiers that can displace other surface active components in the mixtures can significantly influence the efficiency of such procedures. Previously, we investigated interfacial mechanisms of zein protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement. In this paper, we further investigated a different class of protein, glutelin, inside corn and proved that glutelin acts as an oil/water emulsifier in an acidic water environment. Furthermore, an extended surfactant's protein disordering and removal ability was tested and compared with a conventional surfactant. An extended surfactant contains a poly(propylene oxide) or poly(propylene oxide)-poly(ethylene oxide) chain inserted between the hydrophilic head and the hydrophobic tail. In this study, a nonlinear optical spectroscopic technique, sum frequency generation (SFG) vibration spectroscopy, was used to study the behavior of glutelin and extended as well as regular surfactants at the corn oil/water or aqueous solution interface. In most cases, the conventional surfactant shows better protein disordering or removal ability than the extended surfactant. However, with the addition of heat and salt to an extended surfactant solution, the experiment resulted in a substantial increase in the extended surfactant's protein disorder or removal ability.
Subject(s)
Pulmonary Surfactants , Surface-Active Agents , Surface-Active Agents/chemistry , Corn Oil , Zea mays , Glutens , Emulsifying Agents/chemistry , LipoproteinsABSTRACT
Malaysia is one of the top exporters of palm oil, and although currently facing fierce resistance towards palm oil imports in some parts of the globe, one of the ways to utilize this commodity is by increasing palm biodiesel content in local commercial diesel. However, due to the oxygen-rich nature of biodiesel, its utilization suffers from increased nitrogen oxides (NOx) emission compared to conventional diesel. To mitigate this issue and improve diesel engine performance and emissions using biodiesel-diesel blends, this study attempted to investigate implementation of a real-time non-surfactant emulsion fuel supply system (RTES) which produces water-in-diesel emulsion as fuel without surfactants. NOx reducing capability of water-in-diesel produced by RTES has been well documented. Therefore, in this study, 30% biodiesel-diesel (B30) was used as the base fuel while B30-derived emulsions consisting of 10 wt%, 15 wt% and 20 wt% water content were supplied into a 100 kVA, 5.9-L common rail turbocharged diesel engine electric generator. Fuel consumption and exhaust emissions were measured and compared with commercially available Malaysian low grade diesel fuel (D2M). Evidence suggested that emulsified B30 biodiesel-diesel produced by RTES was able to increase brake thermal efficiency (BTE) up to a maximum of 36% and reduce brake specific fuel consumption (BSFC) up to 8.70%. Furthermore, B30 biodiesel-diesel emulsions produced significantly less NOx, carbon monoxide and smoke at high engine load. In conclusion, B30 biodiesel-diesel emulsions can be readily utilized in current diesel engines without compromising on performance and emissions.
Subject(s)
Pulmonary Surfactants , Surface-Active Agents , Emulsions , Biofuels , Palm Oil , LipoproteinsABSTRACT
Dyslipidemia is common in patients with chronic kidney disease. Curcumin, a bioactive polyphenol from Curcuma longa, can improve lipid profile. This study aims to analyze the effects of Curcuma Longa extract supplementation on lipid profile and lipoprotein subfractions in hemodialysis (HD) patients. This is a longitudinal, double-blind, washout-period randomized clinical trial. The patients were randomized into two groups: the curcumin group (n = 10) (orange and carrot juice with 2.5 g of Curcuma Longa extract) and the control group (n = 11) (juice without curcumin) 3x/w during HD sessions for 3 months. After the washout period, patients continued the supplementation as a crossover for the same period. The lipid profile was measured using enzymatic assays. The high-density lipoprotein and low-density lipoprotein subfractions analyses were performed using LipoprintTM. In the curcumin group, the triglyceride values tended to decrease with a different triglyceride variation between the pre and post-intervention for the control and curcumin groups of 38.5 (19.8) mg/dL (p = 0.06). There was no statistical difference in the others parameters. In conclusion, Curcuma longa extract may be a good nutritional strategy to reduce triglyceride plasma levels in hemodialysis patients, but it seems ineffective for the other parameter.
Subject(s)
Curcuma , Curcumin , Humans , Curcumin/pharmacology , Plant Extracts/pharmacology , Triglycerides , Lipoproteins , Renal Dialysis , Dietary SupplementsABSTRACT
INTRODUCTION: Hypocholesterolemia results from genetic - both monogenic and polygenic - and non-genetic causes and can sometimes be a source of clinical concern. We review etiologies and sequelae of hypocholesterolemia and therapeutics inspired from genetic hypocholesterolemia. AREAS COVERED: Monogenic hypocholesterolemia disorders caused by the complete absence of apolipoprotein (apo) B-containing lipoproteins (abetalipoproteinemia and homozygous hypobetalipoproteinemia) or an isolated absence of apo B-48 lipoproteinemia (chylomicron retention disease) lead to clinical sequelae. These include gastrointestinal disturbances and severe vitamin deficiencies that affect multiple body systems, i.e. neurological, musculoskeletal, ophthalmological, and hematological. Monogenic hypocholesterolemia disorders with reduced but not absent levels of apo B lipoproteins have a milder clinical presentation and patients are protected against atherosclerotic cardiovascular disease. Patients with heterozygous hypobetalipoproteinemia have somewhat increased risk of hepatic disease, while patients with PCSK9 deficiency, ANGPTL3 deficiency, and polygenic hypocholesterolemia typically have anunremarkable clinical presentation. EXPERT OPINION: In patients with severe monogenic hypocholesterolemia, early initiation of high-dose vitamin therapy and a low-fat diet are essential for optimal prognosis. The molecular basis of monogenic hypocholesterolemia has inspired novel therapeutics to help patients with the opposite phenotype - i.e. elevated apo B-containing lipoproteins. In particular, inhibitors of PCSK9 and ANGPTL3 show important clinical impact.
Subject(s)
Hypobetalipoproteinemias , Proprotein Convertase 9 , Humans , Hypobetalipoproteinemias/complications , Hypobetalipoproteinemias/genetics , Hypobetalipoproteinemias/therapy , Apolipoproteins B/genetics , Lipoproteins , Cholesterol , Angiopoietin-Like Protein 3ABSTRACT
Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Cerebrovascular Disorders , Dementia, Vascular , Humans , Cholesterol, HDL , Ceramides , Prospective Studies , Lipoproteins/metabolism , TriglyceridesABSTRACT
High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins.
Subject(s)
Fatty Acids, Omega-3 , Animals , Rats , Arachidonic Acid , Cross-Over Studies , Dietary Supplements , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/pharmacology , Endothelial Cells , Fatty Acids , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Lipoproteins , Triglycerides , HumansABSTRACT
Protein-energy malnutrition still impacts children's growth and development. We investigated the prolonged effects of egg supplementation on growth and microbiota in primary school children. For this study, 8-14-year-old students (51.5% F) in six rural schools in Thailand were randomly assigned into three groups: (1) whole egg (WE), consuming 10 additional eggs/week (n = 238) (n = 238); (2) protein substitute (PS), consuming yolk-free egg substitutes equivalent to 10 eggs/week (n = 200); and (3) control group (C, (n = 197)). The outcomes were measured at week 0, 14, and 35. At the baseline, 17% of the students were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the C group the weight and height difference increased significantly in the WE group (3.6 ± 23.5 kg, p < 0.001; 5.1 ± 23.2 cm, p < 0.001). No significant differences in weight or height were observed between the PS and C groups. Significant decreases in atherogenic lipoproteins were observed in the WE, but not in PS group. HDL-cholesterol tended to increase in the WE group (0.02 ± 0.59 mmol/L, ns). The bacterial diversity was similar among the groups. The relative abundance of Bifidobacterium increased by 1.28-fold in the WE group compared to the baseline and differential abundance analysis which indicated that Lachnospira increased and Varibaculum decreased significantly. In conclusion, prolonged whole egg supplementation is an effective intervention to improve growth, nutritional biomarkers, and gut microbiota with unaltered adverse effects on blood lipoproteins.
Subject(s)
Gastrointestinal Microbiome , Adolescent , Child , Humans , Body Weight , Dietary Supplements , Eggs , LipoproteinsABSTRACT
COVID-19 infections decrease total cholesterol, LDL-C, HDL-C, and apolipoprotein A-I, A-II, and B levels while triglyceride levels may be increased or inappropriately normal for the poor nutritional status. The degree of reduction in total cholesterol, LDL-C, HDL-C, and apolipoprotein A-I are predictive of mortality. With recovery lipid/lipoprotein levels return towards pre-infection levels and studies have even suggested an increased risk of dyslipidemia post-COVID-19 infection. The potential mechanisms for these changes in lipid and lipoprotein levels are discussed. Decreased HDL-C and apolipoprotein A-I levels measured many years prior to COVID-19 infections are associated with an increased risk of severe COVID-19 infections while LDL-C, apolipoprotein B, Lp (a), and triglyceride levels were not consistently associated with an increased risk. Finally, data suggest that omega-3-fatty acids and PCSK9 inhibitors may reduce the severity of COVID-19 infections. Thus, COVID-19 infections alter lipid/lipoprotein levels and HDL-C levels may affect the risk of developing COVID-19 infections.