Lipid Transport System Research Articles

Temporal genome-wide fitness analysis of Mycobacterium marinum during infection reveals the genetic requirement for virulence and survival in amoebae and microglial cells.

Tuberculosis remains the most pervasive infectious disease and the recent emergence of drug-resistant strains emphasizes the need for more efficient drug treatments. A key feature of pathogenesis, conserved between the human pathogen Mycobacterium tuberculosis and the model pathogen Mycobacterium marinum, is the metabolic switch to lipid catabolism and altered expression of virulence genes at different stages of infection. This study aims to identify genes involved in sustaining viable intracellular infection. We applied transposon sequencing (Tn-Seq) to M. marinum, an unbiased genome-wide strategy combining saturation insertional mutagenesis and high-throughput sequencing. This approach allowed us to identify the localization and relative abundance of insertions in pools of transposon mutants. Gene essentiality and fitness cost of mutations were quantitatively compared between in vitro growth and different stages of infection in two evolutionary distinct phagocytes, the amoeba Dictyostelium discoideum and the murine BV2 microglial cells. In the M. marinum genome, 57% of TA sites were disrupted and 568 genes (10.2%) were essential, which is comparable to previous Tn-Seq studies on M. tuberculosis and M. bovis. Major pathways involved in the survival of M. marinum during infection of D. discoideum are related to DNA damage repair, lipid and vitamin metabolism, the type VII secretion system (T7SS) ESX-1, and the Mce1 lipid transport system. These pathways, except Mce1 and some glycolytic enzymes, were similarly affected in BV2 cells. These differences suggest subtly distinct nutrient availability or requirement in different host cells despite the known predominant use of lipids in both amoeba and microglial cells.IMPORTANCEThe emergence of biochemically and genetically tractable host model organisms for infection studies holds the promise to accelerate the pace of discoveries related to the evolution of innate immunity and the dissection of conserved mechanisms of cell-autonomous defenses. Here, we have used the genetically and biochemically tractable infection model system Dictyostelium discoideum/Mycobacterium marinum to apply a genome-wide transposon-sequencing experimental strategy to reveal comprehensively which mutations confer a fitness advantage or disadvantage during infection and compare these to a similar experiment performed using the murine microglial BV2 cells as host for M. marinum to identify conservation of virulence pathways between hosts.

Dynamic players and intricate interactions: An integrated investigation of the Mla lipid transport system

The Maintenance of outer membrane (OM) Lipid Asymmetry system mediates retrograde phospholipid transport from the OM to the inner membrane (IM) in Gram-negative bacteria. However, the interactions between the various subunits of the IM and OM complexes are not well understood. In a recent study in 2023 by MacRae etal. in the Journal of Biological Chemistry, the authors examine components in the Maintenance of OM Lipid Asymmetry complex, define the interaction interfaces between members of the pathway, and propose a molecular model of the lipid transfer process from the OM to the IM that will help elucidate intricacies of lipid transport.

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities.

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of "the more the better", ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.

Protein–protein interactions in the Mla lipid transport system probed by computational structure prediction and deep mutational scanning

The outer membrane (OM) of Gram-negative bacteria is an asymmetric bilayer that protects the cell from external stressors, such as antibiotics. The Mla transport system is implicated in the Maintenance of OM Lipid Asymmetry by mediating retrograde phospholipid transport across the cell envelope. Mla uses a shuttle-like mechanism to move lipids between the MlaFEDB inner membrane complex and the MlaA-OmpF/C OM complex, via a periplasmic lipid-binding protein, MlaC. MlaC binds to MlaD and MlaA, but the underlying protein-protein interactions that facilitate lipid transfer are not well understood. Here, we take an unbiased deep mutational scanning approach to map the fitness landscape of MlaC from Escherichia coli, which provides insights into important functional sites. Combining this analysis with AlphaFold2 structure predictions and binding experiments, we map the MlaC-MlaA and MlaC-MlaD protein-protein interfaces. Our results suggest that the MlaD and MlaA binding surfaces on MlaC overlap to a large extent, leading to a model in which MlaC can only bind one of these proteins at a time. Low-resolution cryo-electron microscopy (cryo-EM) maps of MlaC bound to MlaFEDB suggest that at least two MlaC molecules can bind to MlaD at once, in a conformation consistent with AlphaFold2 predictions. These data lead us to a model for MlaC interaction with its binding partners and insights into lipid transfer steps that underlie phospholipid transport between the bacterial inner and OMs.

Evolutionarily conserved aspects of animal nutrient uptake and transport in sea anemone vitellogenesis

The emergence of systemic nutrient transport was a key challenge during animal evolution, yet it is poorly understood. Circulatory systems distribute nutrients in many bilaterians (e.g., vertebrates and arthropods) but are absent in non-bilaterians (e.g., cnidarians and sponges), where nutrient absorption and transport remain little explored at molecular and cellular levels. Vitellogenesis, the accumulation of egg yolk, necessitates high nutrient influx into oocytes and is present throughout animal phyla and therefore represents a well-suited paradigm to study nutrient transport evolution. With that aim, we investigated dietary nutrient transport to the oocytes in the cnidarian Nematostella vectensis (Anthozoa). Using a combination of fluorescent bead labeling and marker gene expression, we found that phagocytosis, micropinocytosis, and intracellular digestion of food components occur within the gonad epithelium. Pulse-chase experiments further show that labelled fatty acids rapidly translocate from the gonad epithelium through the extracellular matrix (ECM) into oocytes. Expression of conserved lipid transport proteins vitellogenin (vtg) and apolipoprotein-B (apoB) and colocalization of labeled fatty acids with a fluorescently tagged ApoB protein further support the lipid-shuttling role of the gonad epithelium. Complementary oocyte expression of very low-density lipoprotein receptor (vldlr) orthologs, which mediate endocytosis of bilaterian ApoB- and Vtg-lipoproteins, supports that this evolutionarily conserved ligand/receptor pair underlies lipid transport during sea anemone vitellogenesis. In addition, we identified lipid- and ApoB-rich cells with potential lipid transport roles in the ECM. Altogether, our work supports a long-standing hypothesis that an ECM-based lipid transport system predated the cnidarian-bilaterian split and provided a basis for the evolution of bilaterian circulatory systems.

The plasma proteome is favorably modified by a high protein diet but not by additional resistance training in older adults: A 17-week randomized controlled trial.

BackgroundThe age-related loss of muscle mass significantly contributes to the development of chronic diseases, loss of mobility and dependency on others, yet could be improved by an optimized lifestyle.ObjectiveThe goal of this randomized controlled trial was to compare the influence of a habitual diet (CON) with either a diet containing the recommended protein intake (RP) or a high protein intake (HP), both with and without strength training, on the plasma proteome in older adults.MethodsOne hundred and thirty-six women and men (65–85 years) were randomly assigned to three intervention groups. CON continued their habitual diet; participants of the HP and RP group consumed either high protein or standard foods. After 6 weeks of dietary intervention, HP and RP groups additionally started a strength training intervention twice per week for 8 weeks. Twenty-four hours dietary recalls were performed every 7–10 days. Body composition was assessed and blood taken. Plasma proteomics were assessed with LC-MS.ResultsParticipants of the HP group doubled their baseline protein intake from 0.80 ± 0.31 to 1.63 ± 0.36 g/kg BW/d; RP increased protein intake from 0.89 ± 0.28 to 1.06 ± 0.26 g/kg BW/d. The CON group kept the protein intake stable throughout the study. Combined exercise and HP initiated notable changes, resulting in a reduction in bodyfat and increased muscle mass. Proteomics analyses revealed 14 significantly affected proteins by HP diet, regulating innate immune system, lipid transport and blood coagulation, yet the additional strength training did not elicit further changes.ConclusionsCombined HP and resistance exercise in healthy older adults seem to induce favorable changes in the body composition. Changes in the plasma proteome due to the high protein diet point to a beneficial impact for the innate immune system, lipid transport and blood coagulation system, all of which are involved in chronic disease development.Clinical trial registrationThe study was registered at ClinicalTrials.gov (NCT04023513).

Integrative analysis of transcriptomics and proteomics of longissimus thoracis of the Hu sheep compared with the Dorper sheep

Meat quality is becoming more important for sheep breeding programs. Meat quality is a complex trait affected by genetic and environmental factors. In the present study, an integrative analysis of the longissimus thoracis tissue transcriptome and proteome was conducted to identify genes, proteins, and pathways related to meat quality in sheep. The sheep breeds Hu and Dorper were considered. These breeds were compared for the differences in muscle fiber structure, chemical composition, and amino acid composition. In the Hu sheep vs. Dorper sheep comparison, 22 DEGs/DEPs showed the same mRNA and protein expression trends. These genes are associated with lipid transport, lipid metabolism, and muscular system development. Moreover, some pathways such as “lipid transport”, “lipoprotein metabolic process”, “Alanine, aspartate and glutamate metabolism”, and “Arginine biosynthesis” were significantly enriched in this study. The reliability of the RNA-Seq results was verified by qRT-PCR. These findings provide new insights into the molecular mechanisms of meat quality in sheep.

Application possibilities of PCSK9 inhibitors in patients with coronary heart disease in combination with type 2 diabetes mellitus

Introduction. Coronary heart disease (CHD) combined with type 2 diabetes mellitus (DM) requires enhanced secondary prevention.The aim of the study was to evaluate the application possibilities of PCSK9 inhibitors in patients with coronary heart disease combined with type 2 diabetes.Materials and methods. The study included 77 patients with coronary heart disease divided into 2 groups: the first group without type 2 diabetes (n=39) and the second group with concomitant type 2 diabetes (n=38). Before the experiment started all patients received a combination of the maximum tolerated dose of atorvastatin and ezetimibe and did not reach the target values of low-density lipoprotein cholesterol (LDL cholesterol), after that alirocumab was added to treatment. In all patients, for 12 months, the parameters of the lipid transport system, glycated hemoglobin and the dynamics of changes in the thickness of the intima-media complex of the carotid arteries were evaluated.Results. After starting treatment with alirocumab, in the first group, LDL cholesterol targets reached 97.4 % (n=38), in the second group – 94.7 % (n=36). The LDL cholesterol level in the first group decreased from 2.27 [2.21; 2.35] to 1.15 [1.07; 1.28] mmol/l (by 49.1 %, p<0.001), in the second group from 2.32 [2.27; 2.36] to 1.17 [1.12; 1.19] mmol/l (by 49.6 %, p<0.001). A direct strong statistically significant correlation was revealed between the concentration of LDL cholesterol and other indicators of lipid metabolism.Conclusion. The obtained results of PCSK9 inhibitors appliance in CHD patients with very high cardiovascular risk demonstrate a decrease in LDL cholesterol by 73.9 % in the group of CHD patients and by 74.2 % in the group of CHD patients in combination with type 2 diabetes. In the first group, the target concentrations of LDL cholesterol were reached by 97.4 % of patients, in the second group – 94.7 %. The achieved hypolipidemic effect was simultaneously combined with a decrease in the thickness of the intima-media complex in the group of patients with coronary artery disease: for the right common carotid artery by 7.8 %, for the left by 10.9 %; in patients with coronary heart disease with concomitant type 2 diabetes: for the right common carotid artery by 8.3 %, for the left by 8.1 %.

The importance of laboratory parameters of the lipid transport system and adipose tissue hormones in assessing the course of chronic.

The main manifestations of metabolic syndrome (MS) are disorders of carbohydrate and lipid metabolism and their hormonal regulation. The combined nature of metabolic disorders can significantly affect the course and prognosis of CHF in elderly people with metabolic syndrome. To determine the features of the combined effect of metabolic laboratory parameters and biological active factors of adipose tissue in patients with CHF and metabolic syndrome on the course of the disease. A comparison was made between a group of patients with CHF complicated by MS(n=37) and a group of patients with CHF without MS (n=37). The parameters of lipid metabolism (cholesterol CH and lipoproteins LP), the lipid transport system (ApoA1 and ApoB), leptin, adiponectin and resistin and their mutual relations were studied. The ratio of ApoB/ApoAI levels was indicative, which was 0.80±0.32 in patients with CHF without MS, and 1.12±0.46 in patients with CHF with MS (p <0.05). A significant correlation was found between the ratio of ApoB/ApoA1 levels and abdominal obesity (r=0.42, p<0.05), functional class of CHF (r=0.463, p<0.05), LDL-C level (r=0.518, p<0.05), and triglycerides (r=0.476, p<0.05). Also, significant results were obtained for the leptin/adiponectin ratio. For this ratio, 4 ranks were derived depending on the value of the leptin (ng/ml)/adiponectin (mcg/ml) ratio: less than 1 - rank 0 was assigned, with values of the ratio in the range 1 - 3 - rank 1, in the range 3.1 - 6 - rank 2, and above the value 6 - rank 3. Of the 22 patients who had improved CHF at the end of hospitalization, all at the beginning of hospitalization had a rank 0 or 1 ApoB/ApoA1 ratio. Thus, ranking the values of the ratio of ApoB/ApoA1 levels, and especially leptin/adiponectin, can suggest the probability of successful treatment of CHF or the probability of deterioration of the patient's condition, up to a fatal outcome.

Роль нарушений липидного обмена и эндотелиальной дисфункции в формировании вертебробазилярной недостаточности у лиц молодого возраста

Актуальность. В патогенезе формирования сосудистой патологии мозга значимую роль играет не только внешний негативный (спондилогенный) фактор, но и дисбаланс различных эндогенных систем (эндотелиальной, липидной), влияющих на церебральную гемодинамику. Следовательно, актуальность изучения этих взаимосвязей имеет не только теоретическое, но и важное практическое значение.Целью исследования было изучение состояния липидного обмена и функции эндотелия у пациентов молодого возраста со спондилогенной вертебрально-базилярной недостаточностью. Материалы и методы. Нами было обследовано 98 пациентов (женщин — 56, мужчин — 42) с проявлениями вертебрально-базилярной недостаточности на фоне мышечно-рефлекторных, нейрососудистых и корешковых синдромов остеохондроза шейного отдела позвоночника. В исследование были включены больные от 18 до 40 лет (средний возраст 28,5 ± 3,8 года). Всем пациентам проводилась функциональная рентгенография шейного отдела позвоночника со сгибанием и разгибанием, МРТ шейного отдела позвоночника, а также ультразвуковое допплерографическое исследование сосудов шеи и магистральных артерий головы с применением функциональных нагрузок с ротацией головы, а также дуплексное сканирование сосудов шеи. Показатели липидного обмена в сыворотке крови определяли спектрофотометрическим методом, концентрацию эндотелина-1 в сыворотке крови — методом иммуноферментного анализа, cодержание S-NO — спектрофлюориметрическим методом.В результате проведенного исследования было выявлено, что спондилогенная вертебрально-базилярная недостаточность сопровождается нарушением обмена липидов, характеризующимся разнонаправленными сдвигами уровня холестерина, липопротеидов низкой плотности, липопротеидов очень низкой плотности и липопротеидов высокой плотности, свидетельствующим о сдвиге плазменных показателей липидтранспортной системы в сторону атерогенеза. Эндотелиальная дисфункция у данного контингента больных характеризуется увеличением концентрации эндотелина-1, являющегося вазоконстрикторным фактором на фоне уменьшения активного метаболита оксида азота — S-NO, обладающего вазодилатирующими свойствами.

Disorders of lipid metabolism and lipid transport system in women with unstable angina in the dependence on smoking: pathogenetic connections and development risks

The aim of the study. To study the effect of smoking on lipid metabolism, lipid transport system and systemic inflammation, to find out their correlations and the risks of unstable angina in women, depending on the habit of smoking.Material and methods. 225 women were examined: 150 women - patients with unstable angina and 75 healthy women. The level of total cholesterol, low and high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 (ApoA1) and B (ApoB), C-reactive protein, fibrinogen were determined in all subjects. Multifactor correlation-regression analysis was performed using Fisher's test. Statistical processing of the results was performed using the applications "Microsoft Office Excel 2016" and "Statistics ver. 10.Results. The relative risk of developing unstable angina in patients with a smoking habit is most often associated with atherogenic dyslipidemia (total cholesterol &gt; 4 mmol, OR = 12.02, SI = 8.12-16.32; low-density lipoprotein cholesterol &gt; 1.8 mmol / l, OR = 9,32, SI = 6,13-12,56, high-density lipoprotein cholesterol &lt;1,2 mmol / l, OR = 3,91, SI = 2,12-5,45, the ratio of apolipoproteins ApoV / ApoA1&gt; 0.85, OR = 2.69, SI = 1.15-4.21) and the highest activity of systemic inflammation (C-reactive protein &gt;3 mg / l, OR = 3.62, SI = 2.15- 4.56). The risk of developing unstable angina associated with these indicators is 1.5-2 times higher in women with a smoking habit than in women who have never smoked. Significant direct correlations of high and medium strength between the severity of systemic inflammation, disorders of the lipid transport system (increase in the ratio of ApoB / ApoA1 and decrease in the level of ApoA1), in patients with unstable angina in women smokers.Conclusions. Smoking is one of the most aggressive factors of unstable angina in women, which contributes to the emergence and progression of other important risk factors and leads to disorders of lipid metabolism, lipid transport system, systemic inflammation and increased chances of unstable angina.

The drug response of pcsk9 inhibitors in the correction of the lipid transport system in patients with ischemic heart disease with diabetes type II

Background and Aims: To assess the degree of variation in the development of the lipid transport system in patients with ischemic heart disease with diabetes mellitus type II as a result of pharmacological correction by PCSK9 inhibitors.

The Interconnection of Insulin Resistance Indices with Metabolic Factors of Cardiovascular Risk in Patients with Hypertension

Background: Among the risk factors (RF) of cardiovascular diseases, insulin resistance (IR) occupies one of the main places. Objective: To identify possible association of insulin resistance (IR) indices with metabolic factors (MF) of cardiovascular risk (CVR) in patients (pts) with essential hypertension (EH). Materials and methods: The prospective study involved 255 patients with EH of I—III stages. Patients were divided into four groups by two IR indices (triglyceride-glucose index (TGGI) and atherogenic index of blood plasma (AIBP)): IR presence was considered at TGGI>4.82 and AIBP>0.21. The state of lipid transport system and system of lipoprotein lipolysis were additionally estimated by calculation of lipid ratios such as non-HDL- C/TC, TC/HDL-C and TG/HDL-C. The results: It has been established that in patients with atherogenic dyslipidemia, the association of IR indices (TGGI and AIBP) as MF of CVR was implemented via disturbances in the system of lipoprotein lipolysis of TG-containing lipoproteins and in the system of reverse cholesterol transport. The association of TGGI and AIBP with hyperglycemia and changes of uric acid (UA) levels was realized through such MF of CVR as glucose intolerance, type 2 diabetes mellitus and elevated UA levels (predominantly in women). In pts with EH and IR, the TGGI was mostly associated with such MF of CVR as increased body mass index (BMI) due to body fat accumulation, while AIBP was mostly associated with body fat lipolysis that was confirmed by the decreased correlation between BMI and parameters of visceral obesity. Conclusions: The most significant (in frequency) MF of CVR associated with IR in pts with EH were hyperglycemia, hypercholesterolemia, elevated levels of TG, low HDL-C, hyperuricemia, as well as BMI elevation due to body fat depositions and activation of their lipolysis confirmed by correlation analysis.

Angiopoietin-like protein 4 promotes very-low-density lipoprotein assembly and secretion in bovine hepatocytes in vitro.

In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin-like protein 4 (ANGPTL4) is a well-known downstream target of peroxisome proliferator-activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very-low-density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two-step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

Features of Disorders of Lipid Metabolism, Lipid Transport System and Systemic Inflammation in Almost Healthy Women Depending on the Habit of Smoking

Introduction. Smoking is one of the most aggressive risk factors for acute coronary heart disease (CHD), especially in women. The number of women smokers in Ukraine has tripled in the last 30 years. Women smokers, even with heavy smoking, are 7 times more likely to suffer from corticosteroids. The issues of the peculiarities of lipid metabolism disorders, lipid transport system and systemic inflammation in practically healthy women, depending on the smoking habit, have not been studied enough, and therefore are the aim of our study. The aim of the study. To find out the features of disorders of lipid metabolism, lipid transport system and systemic inflammation in almost healthy women, depending on the habit of smoking. Materials and methods. 75 women were involved to the study. Depending smoking habit, all subjects were divided into two groups: almost healthy women smokers (n = 45, mean age 52.78 ± 2.52 years) – experimental group (EG), almost healthy women non-smokers (n = 30, mean age 54.81 ± 3.21 years) – comparison group. To determine the peculiarities of the state of lipid metabolism, the state of the lipid transport system, the activity of systemic inflammation, all subjects were determined indicators of total cholesterol, low-density lipoprotein cholesterol (LDL cholesterol), high-density lipoprotein cholesterol (HDL cholesterol), apolipoproteins A1 (ApoA1), apolipoproteins B (ApoB), calculated the ratio of ApoB / ApoA1, C-reactive protein (CRP) and fibrinogen (FB). Results. It was found that the content in the serum of cholesterol in almost half (48.89 %) of women with a habit of smoking, was greater than 4.50 mmol/l. The mean rate of total cholesterol among these individuals was 5.84 ± 0.05 mmol/l, which was significantly higher than in the cohort of comparison group women with total cholesterol more than 4.50 mmol/l who did not have a smoking habit. Similar trends were observed in the case of comparing the proportions of individuals with LDL cholesterol more than 3.00 mmol/l. In particular, this excess was registered in 31.11 % in women with smoking habit, which is significantly (1.33 times) higher than in women with the comparison group (23.33 %). In contrast, the proportion of surveyed women with a reduced less than 0.96 g/l ApoA1 in women with smoking habit was significantly 1.62 times higher than in the women from the comparison group (37.78 % vs. 23.33 %, p less than 0.05). Also, among these individuals, the average ApoA1 was lower in smokers than among non-smokers (0.91 ± 0.04 g/l vs. 0.96 ± 0.03 g/l, p less than 0.05). The calculation of the ApoB/ApoA1 ratio showed a higher intensity of proatherogenic shift of the lipid spectrum in smokers. Female smokers percentage of persons with a CRP greater than 3.00 mg/ml was 13.34 %, which is twice as much (p less than 0.05) than in the group of non-smokers, in which there were 6 such persons, 6.67 %. Conclusions. Disorders of lipid metabolism, lipid transport system and systemic inflammation in women depending on the habit of smoking have their own characteristics – in women smokers, these disorders are significantly more severe than in women without smoking, and are atherogenic, namely: significantly higher levels of total cholesterol, cholesterol low-density lipoproteins, triglycerides, apolipoprotein B transport proteins, apolipoprotein B / apolipoprotein A1 transport protein ratios, mean values of C-reactive protein and fibrinogen, and lower levels of high-protein lipoprotein A1 protein and high protein lipoproteins.

Lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemia rats based on lipid metabolism disorder

The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.

Characterization of Membrane Contact Sites for the Facilitation of Lipid Exchange at the Malaria Parasite - Red Blood Cell Interface

The malaria parasite maintains lipid homeostasis inside its host red blood cell. To that end, the parasite installs a lipid transport system with an unknown mechanism crossing two aqueous spaces: the red cell cytoplasm and the parasitophorous vacuole. We hypothesized that lipid transport across the parasitophorous vacuole may be facilitated at membrane contact sites. Using thin section electron microscopy, we measured the distance between the parasite plasma membrane (PPM) and the parasitophorous vacuole membrane (PVM). We found that two regions with distinct distances can be defined: 1) “PV lumenal” regions of 20-30 nm membrane distance and 2) regions of membrane apposition with ∼10 nm distance. To have a PV-lumenal label for live-cell microscopy we genetically targeted the fluorophore mRuby3 to the PV (PV-mRuby3). Correct targeting was confirmed using correlative light electron microscopy verifying that the discontinuous PV-mRuby3 signal shows the PV lumenal regions. To look for functions performed in each region, we localized two fluorescently tagged proteins relative to the PV-mRuby3: 1) EXP2, a channel involved in the export of proteins and import of nutrients across the PVM and 2) PfNCR1, a Niemann-Pick homologous lipid transporter in the PPM. Using correlation analysis on 2D projections of the parasite periphery, we found that the presence of EXP2 correlates well with the presence of PV lumen, while PfNCR1 is associated to regions of membrane apposition. Together both proteins complement to outline the periphery of the parasite. We conclude that membrane distance correlates with function of the host-parasite interface. The PV-lumen is a compartment that allows protein processing and storage. Lipid transport at sites of membrane apposition suggests a membrane contact site mediated mechanism for lipid exchange.

Arachnid Hemocyanins.

Hemocyanin (Hc), a copper-containing extracellular multimeric protein, is the major protein component of hemolymph in different arachnid groups. Hc possesses 7 or 8 very well-characterized types of monomers with molecular weights ranging from 70 to 85kDa, organized in hexamers or multiple of hexamers. The present chapter compiles the existing data with relation to the function of this protein in the arachnids. Hc has as main function the reversible transport of O2, but it shows many secondary though not less important functions. With reference to this, it has been described that Hc can transport hydrophobic molecules (lipid-derived hormones and lipids) to the different organs, having a key role in the lipid transport system. In arachnids, like in other arthropods and invertebrates, Hc has phenoloxidase function which is related to different metabolic processes such as melanin formation and defense against pathogens. In addition, Hc has additional defensive functions since it can serve as precursor for the production of antimicrobial peptides. In short, the evolution of this protein has led to the development of multiple functions essential for organisms possessing this protein.

The role of saturated fatty acids in impaired lipid metabolism in patients with alcohol dependence syndrome

To determine the content and role of saturated fatty acids (SFA) in lipid metabolism disorder in patients with alcohol dependence syndrome (ADS). A total of 123 men were examined: 44 patients with ADS and 79 healthy people. The patients were examined on the 5-6 day after admission to the hospital. The content of saturated fatty acids (SFA) (caproic, caprylic, capric, undecyl, lauric, tridecane, myristic, pentadecanoic, palmitic, margarine, stearic, arachin, eicosanoic, behenic) was determined by gas-liquid chromatography. Quantitative calculation of SFA levels was carried out by the AgilentChemStationB.03.01 program (USA). The ratio of stearic to palmitic acid (C18:0/C16:0) was calculated. The study of the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) was carried out by generally accepted standardized methods on a Cobas Mirra automated analyzer. In ADS patients, changes in the composition of SFA were found with an increase in the number of short-chain fatty acids (caproic acid by 52.2%, caprylic acid by 75.5%); medium-chain acids (capric acid by 47.9%, undecyl acid by 74.7%, lauric acid), but with a decrease in the concentration of long-chain acids (pentadecanoic by 5.1%, margarine by 34.7%, arachinic by 19.58%, eicosanoic by 26.6%, behenic by 5.1%). Less correlations between the fatty acid content and the parameters of the lipid transport system of blood serum were established in ADS patients compared to the controls. This indicates deep disorders of lipid metabolism. The results expand the understanding of the complex mechanisms of lipid metabolism disorders in ASD, which is important for secondary prevention. They also substantiate the need for a purposeful study of lipid metabolism disorders in patients with ADS at an earlier stage of the disease.

ATEROSCLEROSIS AND INFLAMMATION: GENERAL PATHOGENETIC MECHANISMS

According to modern notions, atherosclerosis is a complex multifactorial process in which the mechanisms of development involved endothelial dysfunction, inflammation, dyslipidemia, disorders of the blood coagulation system, and the like. Polyunsaturated fatty acids are a source of biologically active substances that regulate metabolic processes in the body. It is known that during the development of inflammation, biologically active agents are synthesized and accumulated, which both provide a protective function, and play the role of triggers or lead to the development of additional alteration and the formation of pathological systems.&#x0D; Purpose of the study. The purpose of the work is to study the functional state of the lipid transport system and to ascertain the role of polyunsaturated fatty acids in the mechanisms of atherosclerosis.&#x0D; The analysis of the functional state of the lipid-transport system of 221 patients with diffuse cardiosclerosis with different nosological forms revealed a disturbance of direct and reverse transport of cholesterol, but with varying degrees of orientation. Significant increase in the content of saturated fatty acids by 7.51% and reduction of unsaturated.&#x0D; Reducing the level of polyunsaturated fatty acids is a consequence of increased formation of prostaglandins and leukotrienes in inflammatory processes of the vascular wall, and indicates a disbalance in the regulation of lipid homeostasis. The deficiency in polyunsaturated fatty acid cells for many years models the high potential of endothelial dysfunction, which can be a pathogenetic mechanism not only for atherosclerotic lesions, but also for inflammation of the vessels.&#x0D; Conclusion. The recognition of atherogenesis as an active process rather than a cholesterol storage disease has highlighted some key inflammatory mechanisms. In our opinion, the local violation of the transport of lipids in the tissue is at the heart of the atherosclerotic lesion of the vascular wall, which develops irrespective of inflammation in the vessel wall, but substantially potentiates them due to the action of inflammatory mediators.