Plasma HDL-C Research Articles

CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1.

C1q tumor necrosis factor-related protein 15 (CTRP15), a newly identified myokine, is closely implicated in cardiovascular disease. However, the role of CTRP15 in atherosclerosis is still unclear. This study aims to determine the role of CTRP15 in atherosclerosis and explore the underlying mechanisms. Our findings revealed that lentivirus-mediated CTRP15 overexpression significantly decreased atherosclerotic plaque lesions and increased reverse cholesterol transport (RCT) efficiency and circulating HDL-C levels in apolipoprotein E-deficient (apoE-/-) mice. Consistently, in vitro, overexpression of CTRP15 also inhibited intracellular lipid accumulation and promoted cholesterol efflux from macrophages. Mechanistically, CTRP15 decreased the expression of miR-101-3p by upregulating T-cadherin, thereby facilitating ABCA1 expression and cholesterol efflux. In summary, these data indicate that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels via the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.

Supplementation of conventional anti-diabetic therapy with alpha-lipoic acid prevents early development and progression of diabetic nephropathy

BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Current pharmacological interventions only retard DN progression. Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other diabetic complications. This study investigates whether ALA supplementation prevents early development and progression of DN. MethodFifty-eight male Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats served as diabetic control. Blood, kidneys and pancreas were harvested for biochemical and histological analyses. ResultInduction of T2DM resulted in hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation maintained β-cell function, normoinsulinemia and normoglycemia in diabetic rats, and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA supplementation significantly prevented elevated serum and tissue malondialdehyde, collagen deposition, α-SMA expression, apoptosis and serum IL-1β and IL-6 levels while it markedly increased renal glutathione content and plasma HDL-C compared to diabetic control group (p < 0.001). ConclusionALA supplementation prevents early development and progression of DN by exerting anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects. Our findings provide additional option for clinical treatment of DN in T2DM patients.

HDL and Cholesterol Ester Transfer Protein (CETP).

Cholesterol ester transfer protein (CETP) is important clinically and is one of the major targets in cardiovascular disease studies. With high conformational flexibility, its tunnel structure allows unforced movement of high-density lipoproteins (HDLs), VLDLs, and LDLs. Research in reverse cholesterol transports (RCT) reveals that the regulation of CETP activity can change the concentration of cholesteryl esters (CE) in HDLs, VLDLs, and LDLs. These molecular insights demonstrate the mechanisms of CETP activities and manifest the correlation between CETP and HDL. However, animal and cell experiments focused on CETP give controversial results. Inhibiting CETP is found to be beneficial to anti-atherosclerosis in terms of increasing plasma HDL-C, while it is also claimed that CETP weakens atherosclerosis formation by promoting RCT. Currently, the CETP-related drugs are still immature. Research on CETP inhibitors is targeted at improving efficacy and minimizing adverse reactions. As for CETP agonists, research has proved that they also can be used to resist atherosclerosis.

HDL and Scavenger Receptor Class B Type I (SRBI).

The scavenger receptor class B type I (SR-BI) is a versatile HDL receptor protein. It is highly expressed in liver and steroidogenic tissues. SR-BI regulates selective uptake of cholesterol ester (CE) from HDL, revealing its role in mediating reverse cholesterol transport (RCT) and steroid hormone synthesis. In addition, SR-BI is involved in cholesterol transport, cellular inflammatory response, platelet reactivity, and HDL-initiated signaling in the vascular system in several mouse models. Mutations in the human SR-BI gene (SCARB1) have been found to be associated with abnormally high plasma HDL-C levels and an increased risk of atherosclerotic cardiovascular disease. At present, the key regions of SR-BI transmembrane structure and the regulatory mechanisms of SR-BI expression still need to be further studied. In this chapter, the structural, functional, and regulatory characteristics of SR-BI are reviewed, and the importance of SR-BI in related metabolic diseases was expounded.

Effects of "Bacuri" Seed Butter (Platonia insignis Mart.) on Metabolic Parameters in Hamsters with Diet-Induced Hypercholesterolemia.

This study aimed to evaluate the effects of the treatment with bacuri seed butter (BB) on body weight, growth, body mass index, lipid profile, atherosclerotic indices, and liver function in dyslipidemic hamsters. Freshly weaned, male hamsters were divided into four groups: (1) normal group (NG)—maintained with standard chow (AIN-93G); (2) dyslipidemia group (DG)—maintained with hyperlipidemic chow (AIN-93G modified) throughout the follow-up period; (3) bacuri seed butter 25 mg/kg/day (BB-25); and (4) bacuri seed butter 50 mg/kg/day (BB-50). BB groups (25 and 50 mg/kg/day) were also maintained with hyperlipidemic chow throughout the follow-up period, and the treatment started after 21 days receiving a hyperlipidemic diet to induce hypercholesterolemia and maintained for 28 days. No significant differences in triglycerides and total cholesterol were observed for BB-25 and BB-50 groups when compared with NG and DG groups. On the contrary, BB-25 and BB-50 induced both increase of HDL-c (51.40 ± 1.69 and 51.00 ± 2.34, respectively) and decrease of LDL-c (103.80 ± 6.87 and 100.50 ± 3.95, respectively) when compared with DG (41.00 ± 2.94 and 132.70 ± 9.41, respectively). In addition, BB promoted a reduction in the risk of atherosclerotic disease by decreasing (p < 0.05) the atherogenic index, coronary artery risk index, and LDL/CT ratio (p < 0.05) and increasing HDL/CT ratio. On the contrary, no changes were observed in total cholesterol and triglyceride levels or in body weight, growth, body mass index, or liver function parameters. Thus, bacuri seed butter at doses of 25 and 50 mg/kg/day has positive repercussions on the lipid profile, more precisely on plasma HDL-c and LDL-c, and additionally promotes reduction in the risk of atherosclerosis in hamsters.

Abstract 11114: Cardiovascular Disease Burden is Associated with Worsened Clinical Depression

Objective: To examine the association between prevalent cardiovascular diseases (CVDs) and CVD risk factors and depression symptoms in a US general population sample. Methods: US adults in the 2013-14 and 2015-16 National Health and Nutrition Examination Survey were included. CVDs (coronary heart disease [CHD], congestive heart failure [CHF], stroke) and CVD risk factors: current smoking; hypertension [HTN]; diabetes mellitus [DM]; and dyslipidemia; systolic BP (SBP), HbA1C, fasting plasma glucose (FPG), serum cholesterol (C), triglycerides (TG), HDL-C, and LDL-C were based on patient-report or lab tests, or medication prescriptions. The sum of HTN, DM, dyslipidemia, and current smoking represented a CVD risk score variable (range: 0-4). Depression symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9): 0-9 (none-mild); 10-27 (moderate-to-severe). Logistic regression models were used to assess the association between CVDs and moderate-to-severe depression. Results: A total of 12,105 participants (52% females, 64% Caucasians) of mean (SE) age of 46.8 (0.3) years and BMI of 29.2 (0.1) kg/m 2 were included. Moderate-to-severe depression was prevalent among 8.1% of participants. The proportions (%) of CVD risk score categories of 0-4 were: 20.5; 31.4; 32.1; 14.6; 1.5. After adjusting for age, race, sex, BMI, marital and educational status, participants with risk scores of 1; 2; 3; and 4 had 1.3 (95% CI: 0.8-2.1); 2.4 (1.5-3.7); 5.0 (3.2-7.8); and 5.5 (2.9-10.4) times higher odds of having moderate-to-severe depression, compared to those without CVD risk. One percent higher HbA1C and a five mg/dl decrease in HDL-C were associated with 1.1 (95% CI: 1.1-1.2) and 1.0 (95% CI: 1.0-1.1) times higher odds of having moderate-to-severe depression, respectively. Self-reported CHD; stroke; CHF; and any CVD were associated with 3.5 (1.8-6.7); 1.7 (0.7-3.9); 2.1 (1.3-3.4); and 2.1 (1.2-3.6) times higher odds of having moderate-to-severe depression, after additional adjustment for current smoking, LDL-C, SBP, and FPG. Conclusions: Prevalent CVDs and CVD risk factors are significantly associated with depression symptoms in the US general population, underscoring the need to integrate mental and physical healthcare services.

DYNAMICS OF TRADITIONAL MODIFIABLE RISK FACTORS, TOTAL CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID ARTHRITIS ON LONG-TERM IL-6 RECEPTOR ANTAGONIST TREATMENT

TOPIC: Cardiovascular Disease TYPE: Original Investigations PURPOSE: The effect of an inhibitor of interleukin (IL)-6 receptors on the state of the cardiovascular system in patients (pts) with rheumatoid arthritis (RA) remains poorly understood.Objective: To study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors (RF), total cardiovascular risk in RA pts during a 12-month (m) follow-up period. METHODS: The study included 40 pts with active RA (33 women/7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55[49;64]years, the duration of the disease — 102[48;162]m; DAS28 6.2[5.5;6.7]points; all pts were seropositive for rheumatoid factor, 80% for antibodies to cyclic citrullinated peptide. Pts received TCZ 8mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All pts underwent an assessment of traditional RF and were determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (TG) levels. The total cardiovascular risk was calculated using the mSCORE. RESULTS: After 12m of TCZ therapy, a decrease in disease activity was noted: remission was observed in 64% (n=25) of pts, low disease activity - in 31% (n=12). DAS28, HAQ, CRP and ESR concentrations decreased significantly. ? high frequency of traditional RF was found in RA pts: dyslipidemia - 67%, arterial hypertension - 65%, overweight - 55%, burdened heredity for cardiovascular diseases - 35%, smoking - 15%. Every third pts had a combination of three or more traditional RF. After 12 m of TCZ therapy, the frequency of traditional RF did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index (IA) by 28% (p<0.01). Moreover, an increase in the level of HDL-C by the finish was found in pts regardless of statin therapy. Changes in the concentration of other lipids during the observation, including during therapy with statins, were not observed. A negative correlation the dynamics of the levels of ?TC and ?CRP (R=−0,37, p<0.05), ? LDL-C and ?CRP (R=−0,42, p<0.01) was found. A very high cardiovascular risk according to the SCORE scale was determined in 78% of pts, moderate - in 2%, and low - in 20% of pts. The distribution of pts by mSCORE value and level of cardiovascular risk were not documented after 12m of TCZ therapy. CONCLUSIONS: After 12 m of TCZ therapy resulted in decreased RA activity, increased the level of HDL-C, IA, BMI; the frequency of traditional RF and the total cardiovascular risk did not change. Despite the very high risk of developing CVD associated with the inflammatory activity of RA, the accumulation of traditional RF and their combination. Insufficient effectiveness of statin therapy was revealed. CLINICAL IMPLICATIONS: cardiovascular risk, rheumatoid arthritis, therapy with an inhibitor of IL-6 receptors DISCLOSURES: No relevant relationships by Elena Gerasimova, source=Web Response No relevant relationships by Yulia Gorbunova, source=Web Response No relevant relationships by Alexandra Martynova, source=Web Response No relevant relationships by Tatiana Popkova, source=Web Response

Effect of melatonin on C-reactive protein and lipid profile of hemodialysis patients

Introduction: Cardiovascular disease is one of the major causes of death in hemodialysis patients. Lipid metabolism abnormalities and increased inflammatory factors are related factors. In recent studies, melatonin inhibits dyslipidemia and reduces inflammatory factors by inhibiting LDL-C oxidation. The purpose of this study was to evaluate the effect of melatonin supplement on hyperlipidemia and C-reactive protein (CRP) level in hemodialysis patients. Objectives: We aimed to determine the effect of melatonin on CRP and lipid profile of hemodialysis patients. Patients and Methods: Among 200 hemodialysis patients, only 28 patients fulfilled the inclusion criteria to enroll in the study. Patients were treated with melatonin supplements 3 mg/d at bedtime for 12 weeks. Serum lipid profile and CRP levels were measured after 12 weeks. Five patients were excluded, 2 patients underwent kidney transplantation, and three patients did not cooperate. The Wilcoxon signed-rank test was used to compare the two groups according to the number of participants (less than 30) and study type (pre-test and post-test). P &lt;0.05 was considered as the level of significance. Results: A total of 23 patients completed the treatment protocol. Participants was composed of 13 male and 10 female. The participants’ mean age was 30.6± 11.6 years. After treatment mean total cholesterol levels decreased from 139.95±35.49 mg/dL to 131.13 ± 34.96 mg/dL (P=0.194) which was not statistically significant. However, the decrease in serum triglyceride level was statistically significant (P=0.004). Plasma HDL-C increased significantly after treatment (P=0.032). Serum CRP levels did not change. Conclusion: Melatonin supplement improves serum triglyceride and HDL-C levels in hemodialysis patients but has no effect on total cholesterol and CRP in hemodialysis patients. Trial Registration: This randomized controlled trial was registered by the Iranian Registry of Clinical Trials (identifier: IRCT20200308046724N1; https://en.irct.ir/trial/46407, ethical code; IR.SBMU.RETECH.REC.1397.687).

861Mendelian randomization on habitual coffee intake and plasma lipid profile: evidence from UK Biobank

Abstract Background Long-term heavy coffee consumption may adversely affect individuals’ cardiovascular disease (CVD) risk. As hyperlipidemia is a well-established contributor to CVD, we investigated the association between habitual coffee intake and plasma lipid profile. Methods We used data from up to 362,571 UK Biobank participants to examine associations between coffee intake and plasma lipid profiles, including LDL-C, HDL-C, total-C, triglycerides, ApoA1 and ApoB. Inverse variance weighted mendelian randomization (MR) was used to interrogate the causal nature of coffee-lipid associations, complemented by pleiotropy-robust methods, including MR-median, MR-Mode, MR-PRESSO and MR-Egger. Results We observed positive dose-dependent associations between self-reported coffee intake and plasma concentration of LDL-C, ApoB and total-C, with the highest lipid levels seen among participants drinking &amp;gt;6 cups/day (Plinear trend≤1.97E-57 for all). Genetic instrument for coffee intake was robustly associated with self-reported intake in the UK Biobank (F-statistic = 416). One cup increase in genetically instrumented intake was associated with 0.07 mmol/L (95%CI 0.03 to 0.12), 0.02 g/L (95%CI 0.01 to 0.03), and 0.09 mmol/L (95%CI 0.04 to 0.14) increase in LDL-C, ApoB, and total-C, respectively. Pleiotropy-robust methods provided largely consistent results albeit with greater imprecision when using MR-Egger. Conclusions Our phenotypic and genetic analysis consistently suggests that long-term heavy coffee consumption can lead to unfavourable lipid profile, which could potentially increase individuals’ risk for CVD. Individuals with elevated cholesterol may need to reduce their daily coffee intake. Key messages Our study provides evidence that long-term heavy coffee consumption can lead to unfavourable lipid profile.

Connection between the Plasma Level of Apelin and Diabetic Nephropathy in Type 2 Diabetic Patients. A Case Control Study.

Background:Apelin is an adipokine that may have an advantageous role in the prediction of early diabetic nephropathy. A few studies on apelin in diabetes have been performed and this research was performed to establish the connection between the apelinergic system and diabetic nephropathy.Materials and Methods:The research included 60 patients with type 2 diabetes mellitus (T2DM) who were equally divided into Group-I (diabetic nephropathy) and Group-II (non-diabetic nephropathy), and 30 healthy subjects in the control group (Group-III). Body mass index (BMI) and waist circumference were calculated. FBG, 2 h–PPG, HbA1c, fasting lipids, urea, creatinine, eGFR, urine analysis, A/C ratio, and apelin levels were assessed.Results:A statistically significant between-group difference in plasma apelin levels was found (P < 0.001). Apelin was the highest in Group-I than in Group-II relative to Group-III (325.79 ± 59.42 pg/mL, 162.83 ± 29.88 pg/mL, and 77.43 ± 8.44 pg/mL, respectively). Among diabetic patients, plasma apelin had a significantly positive correlation with disease duration (r = 0.612), SBP (r = 0.427), DBP (r = 0.466), weight (r = 0.372), and height (r = 0.372), FBG (r = 0.684), 2 h-PPG (r = 0.744), HbA1C (r = 0.890), total (T)-cholesterol (r = 0.316), low density lipoprotein (LDL)-C (r = 0.397), urea (r = 0.575), and creatinine (r = 0.591). A significantly negative correlation was observed between plasma apelin and HDL-C (r = –0.303), and eGFR (r = –0.566).Conclusion:Apelin levels in diabetics were elevated in the case of nephropathy, impaired glucose tolerance, and dyslipidemia. This supports the relationship between the apelinergic system and diabetic nephropathy.

Angiopoietin-Like Proteins 2 and 3 in Children and Adolescents with Obesity and Their Relationship with Hypertension and Metabolic Syndrome.

Background Angiopoietin-like protein 2 (ANGPTL2) is one of the adipocyte-derived inflammatory factors which connects obesity to insulin resistance. ANGPTL3 has a direct role in regulation of lipid metabolism. The objective of this study was to evaluate ANGPTL2 and ANGPTL3 in childhood obesity and their relationship with metabolic syndrome. Methods 70 children and adolescents, 35 obese and 35 normal-weight subjects, were enrolled in this research after complete clinical examination and anthropometric evaluations. Serum ANGPTL2 and ANGPTL3 and insulin were measured by enzyme-linked immunosorbent assay (ELISA). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate insulin resistance (IR). Colorimetric methods were used for the assessment of fasting plasma glucose (FPG), LDL-C, HDL-C, total cholesterol (TC), and triglyceride (TG). Results The levels of ANGPTL2 and ANGPTL3 were significantly higher in obese subjects than those in controls, but they did not differ significantly in subjects with or without IR. ANGPTL3 was found to be significantly elevated in obese children with metabolic syndrome (MetS) in comparison with those without MetS. Both of the studied ANGPTLs were positively correlated with BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, and LDL-C. The correlation between ANGPTL3 and either TC or LDL-C remained significant after adjusting for BMI. Conclusion Serum ANGPTL2 and ANGPTL3 were elevated in obesity and associated with blood pressure and indices of metabolic syndrome, suggesting that they might be involved in the advancement of obesity-related hypertension and metabolic syndrome.

Serum opacity factor normalizes dysfunctional HDL phenotype in SRB1 -/- mice

Background and Aims: Although plasma HDL-C levels negatively correlate with atherosclerotic cardiovascular disease (ACVD), attempts to reduce ACVD risk by raising plasma HDL have disappointed. The SRB1-/- mouse is an extreme model of HDL dsyfunctionality; compared to WT mice, SRB1-/- mice have higher plasma HDL with a free cholesterol (FC)-rich surface (60 vs. 15 mol%). HDL dysfunctionality among SRB1-/- mice is associated with atherosusceptibility and female infertility. Liver-specific SRB1 expression in SRB1-/- mice normalizes HDL size and FC content. Thus, the SRB1-/- mouse phenotype is due to lack of hepatic clearance of dysfunctional HDL. Serum opacity factor (SOF) is a bacterial protein that catalyzes the quantitative disproportionation of HDL into a cholesteryl ester-rich micro emulsion (CERM), neo HDL, and lipid-free apo AI. The CERM contains apo E and all HDL-CE. Injection of SOF into WT mice lowers plasma cholesterol by diverting the CERM to hepatic LDLR. Our studies will determine whether normalizing dysfunctional HDL in SRB1-/- mice by SOF leads to phenotypical changes in female infertility and atherosclerosis in a high-fat diet model.

Relationship between levels of lipid and sleep quality in the elderly diabetic patients at National geriatric hospital

Background: Reduced sleep quality is common in advanced age. Poor sleep quality is associated with adverse outcomes, possibly because of its association with lipid disorder. However, the correlates of sleep quality in older populations are unknown. Objectives: To assess the association of levels of blood lipid with quality of sleep in older diabetic patients treated at National Geriatric Hospital. Methods: A cross-sectional study on 178 older diabetic patients treated at National Geriatric Hospital from March to October, 2020. Quality of sleep was assessed using the Pittsburgh Sleep Quality Index. Results: Among 178 participants, the mean age was 73.5 ± 8.0; female account for 57.3%. The rate of poor sleep quality was 67.4%. There was significant difference between cholesterol concentration and blood pressure ≥ 130/85 mmHg in female and sleep quality with p&lt;0.05. There was no significant difference between fasting plasma glucose, triglyceride and HDL-C level, waist circumference and sleep quality. Conclusion: Our results confirm a high prevalence of poor sleep quality in older diabetic people. Early detection by performing PSQI for screening sleep disturbance in older diabetic patients then give appropriate treatment can help improved effectiveness of treatment as well as the patients’ quality of life.

Comparative study of physicochemical properties, fatty acid composition, antioxidant and toxicological potential of Citrullus lanatus and Citrullus colocynthis seeds oils

Citrullus colocynthis (C. colocynthis) seed is a common and expensive cuisine in West African diet unlike the seeds from Citrullus lanatus (C. lanatus) that are agro waste. The oils from these seeds were comparatively profiled using their physicochemical properties, fatty acids and phenolic contents, in-vitro antioxidant capacity (DPPH, TEAC, FRAP, ORAC), inhibitions of lipid peroxidation and tyrosinase. Toxicities of the oils in mice were also assessed using plasma AST, ALT, cholesterol, HDL-C, liver, heart and kidney (GSH, GPx and SOD) and clastogenic effects in mouse bone marrow. Citrullus lanatus oil contains higher peroxides, saponification, saturated fatty acids and stearic acid (6-fold) levels, with a lower acid value when compared to C. colocynthis. Strong antioxidant capacity, inhibition of lipid peroxidation and tyrosinase by C. lanatus oil extract is proposed to be related to the presence of catechins that are absent in C. colocynthis. The in-vivo study indicated that C. lanatus induced significant increase in ALT while a significant increase of AST was observed in the C. colocynthis treated group. Citrullus lanatus induced a significantly (p<0.05) higher heart GPx activity when compared with C. colocynthis and the control groups. Both oils did not affect SOD activity and showed no clastogenic effect in mouse bone marrow (p>0.05). This work reports for the first time the presence of stearic acid and catechin in C. lanatus oil which is important for its compelling in vitro activity. High doses of both oils could evidently induce toxicological indices in mice.

High-Intensity Interval Training and Moderate-Intensity Continuous Training Attenuate Oxidative Damage and Promote Myokine Response in the Skeletal Muscle of ApoE KO Mice on High-Fat Diet.

The purpose of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the skeletal muscle in Apolipoprotein E knockout (ApoE KO) and wild-type (WT) C57BL/6J mice. ApoE KO mice fed with a high-fat diet were randomly allocated into: Control group without exercise (ApoE−/− CON), HIIT group (ApoE−/− HIIT), and MICT group (ApoE−/− MICT). Exercise endurance, blood lipid profile, muscle antioxidative capacity, and myokine production were measured after six weeks of interventions. ApoE−/− CON mice exhibited hyperlipidemia and increased oxidative stress, compared to the WT mice. HIIT and MICT reduced blood lipid levels, ROS production, and protein carbonyl content in the skeletal muscle, while it enhanced the GSH generation and potently promoted mRNA expression of genes involved in the production of irisin and BAIBA. Moreover, ApoE−/− HIIT mice had significantly lower plasma HDL-C content, mRNA expression of MyHC-IIx and Vegfa165 in EDL, and ROS level; but remarkably higher mRNA expression of Hadha in the skeletal muscle than those of ApoE−/− MICT mice. These results demonstrated that both exercise programs were effective for the ApoE KO mice by attenuating the oxidative damage and promoting the myokines response and production. In particular, HIIT was more beneficial to reduce the ROS level in the skeletal muscle.

Relationships between di-(2-ethylhexyl) phthalate exposure and lipid metabolism in adolescents: Human data and experimental rat model analyses

In recent years, the incidence of lipid metabolism disorders in adolescents has gradually increased, and the effects of DEHP on lipid metabolism have received widespread attention. In this study, 463 adolescents aged 16–19 years were enrolled as subjects. This study analyzed the associations between the urinary levels of DEHP metabolites (MEHP, MEOHP, MEHHP, MECPP, MCMHP, and ∑DEHP) and BMI, WHR, WtHR, VAI, LAP, the plasma levels of lipids (TC, TG, HDL-C, and LDL-C), and the peripheral blood leukocyte mRNA levels of SREBP-2, SR-BI, LDLR, and NR1H3. Animal experiments were performed to confirm and expand findings. Wistar rats were administered DEHP at 0, 5, 50, and 500 mg/kg/d for 8 weeks. The serum and liver levels of TC, TG, HDL-C, and LDL-C, and the liver mRNA and protein levels of SREBP-2, SR-BI, LDLR, and NR1H3 were measured. The results showed that WHR, VAI, and LAP were significantly positively associated with the urinary levels of MECPP and ∑DEHP; the plasma HDL-C level was significantly negatively associated with the levels of MECPP, MCMHP and ∑DEHP; the peripheral blood leukocyte mRNA levels of SREBP-2, NR1H3, and LDLR were significantly positively correlated with the MCMHP level; and the SR-BI mRNA level was significantly positively correlated with the levels of MECPP and MCMHP in adolescents. Moreover, the results of animal experiments showed that DEHP exposure significantly increased the serum levels of TC, HDL-C, and LDL-C in 500 mg/kg/d group, as well as the liver levels of TC and HDL-C, up-regulated SREBP-2 mRNA and protein expression in 50 and 500 mg/kg/d groups. DEHP exposure significantly down-regulated SR-BI and NR1H3 protein expression in the liver of the 500 mg/kg/d group rats. Our findings indicate that DEHP exposure can affect lipid metabolism in adolescents by regulating the expression of lipid metabolism-related genes.

Decaffeinated light-roasted green coffee and green tea extract combination improved metabolic parameters and modulated inflammatory genes in metabolic syndrome rats

Background: Individually, green tea and green coffee have been extensively studied for mitigation of metabolic syndrome (MS) in both rats and humans; however, their combined effect requires further investigation. Thus, we compared the metabolic effect of combining green tea and decaffeinated light roasted green coffee on MS in rats. Methods: An MS animal model was constructed by feeding Sprague-Dawley rats with a high-fat-high-sucrose (HFHS) diet for eight weeks and a low dose of streptozotocin (STZ) injection at week 2. Rats fed with HFHS diets and injected with STZ successfully developed MS phenotypes, indicated by higher body weight, systolic blood pressure, plasma triglyceride level, plasma fasting blood glucose level, and lower plasma HDL-C level, compared to those fed with a normal chow diet. Subsequently, MS rats were continuously fed with HFHS and divided into four groups: MS rats, MS with 300 mg/bw.t green tea extract (GT), MS with 200 mg/bw.t green coffee extract (GC), and MS with combined green tea and green coffee extract (CM) for nine weeks. Results: Combining green tea and green coffee have synergistic effects on reducing plasma fasting blood glucose and triglyceride level. Inflammatory markers both in plasma and liver tissue robustly decreased in CM group rats. However, the reduction of systolic blood pressure was observed only in GT and CM groups. Moreover, all treatment resulted in an increase in plasma HDL-C level in MS rats. Conclusions: Our data highlighted that, in MS animal models, combined green tea and decaffeinated light roasted green coffee augment their several individual beneficial effects of improved metabolic parameters and modulated inflammatory genes.

Relationship Between Metabolic Syndrome and Circulating microRNA Expression in Adults

Abstract Objectives To verify the relationship between circulating miRNA (16, 363, 375, 486, and let7c) expression and risk factors for metabolic syndrome (MetS) in adults. Methods A cross-sectional population-based study including 192 adults without acute inflammatory diseases, cancer, or using medication that would affect the main outcomes. The BioMarkTM Fluidigm Dynamic Array for real-time qPCR was used to quantify miRNA expression levels in plasma. The miRNA expression levels categorized by the MetS status were analyzed by the Mann-Whitney test. The Kruskal-Wallis with post hoc Dunn's tests were used to compare miRNA expression levels categorized by the number of MetS risk factors (0, 1–2, and ≥3). Spearman's correlation between miRNA expression and MetS risk factors was performed. Results The sample included individuals with median age of 41 (20–59) years, 54.7% were women, and 58.3% overweight/obesity. MetS was observed in 33.9% of individuals (15.6% men, and 18.2% women), being increased waist circumference (WC) (67.7%), and reduced plasma HDL-c levels (52.1%) the most prevalent risk factors. Individuals with MetS showed reduced plasma expression of miR-16, −363, −375, and −486, but increased miR-let7c expression compared to the group without MetS (P &amp;lt; 0.05). Analysis of miRNA expression levels categorized according to the number of MetS risk factors demonstrated that individuals without risk factors did not differ from those with 1–2 risk factors. Individuals with 3 or more risk factors differed from all groups, except for the miR-16, which presented difference only in comparison to the group without risk factors. The miR-16 expression correlated negatively with body mass index (BMI) (r = −0.169; P = 0.019), WC (r = −0.153; P = 0.034), diastolic blood pressure (r = −0.144; P = 0.046), and glucose levels (r = −0.171; P = 0.017). The miR-let7c correlated positively with triacylglycerol (r = 0.306; P &amp;lt; 0.001), and negatively with HDL-c (r = −0.173; P = 0.016) levels. The miR-375 correlated negatively with BMI (r = −0.203; P &amp;lt; 0.001), WC (r = −0.187; P &amp;lt; 0.001), and positively with HDL-c levels (r = 0.261; P &amp;lt; 0.001). The miR-486 and −363 correlated negatively with BMI (r = −0.155; P = 0.031 | r = −0.142; P = 0.049, respectively). Conclusions The circulating miRNA evaluated were associated with the risk factors for MetS in adults. Funding Sources São Paulo Research Foundation - FAPESP

Abstract MP12: Proteomic Predictors Of High-density Lipoprotein Cholesterol Response To Regular Exercise

Introduction: Regular exercise beneficially increases plasma HDL-C levels at the group level. However, variation in individual HDL-C responses to exercise highlight a need for predictive biomarkers of exercise response. Hypothesis: We hypothesized that baseline abundance of circulating proteins is predictive of HDL-C response to exercise and that identified proteins are part of a complex biological network of exercise response. Methods: We measured over 5,000 circulating proteins using an aptamer-affinity based platform (SomaScan) in 667 black and white adults from the HERITAGE Family Study. Fasting plasma HDL-C was measured at baseline and following 20 weeks of supervised endurance exercise training. To predict exercise induced changes in HDL-C using baseline abundance of circulating proteins, models were created using LASSO regression and a 70/30 training test data split with 10-fold cross validation. Biological pathways, networks, and functions involving proteins identified in predictive modeling were investigated by ingenuity pathway analysis (IPA) and integrated molecular pathway level analysis (IMPaLA). Results: Regular exercise significantly increased HDL-C in the sample by 1.5 ± 4.6 mg/dL (p&lt;0.0001), however marked inter-individual differences in response were present (range: -19.5 to +17.4 mg/dL). LASSO regression of circulating proteins only yielded a model of 120 proteins with similar but stronger predictive power to a model of 19 clinical traits (root mean square error = 4.52 and 5.3 mg/dL respectively). LASSO regression of both clinical and proteomic predictors resulted in a final model of baseline HDL-C and 116 circulating proteins, with an improved root mean square error of 4.11 mg/dL. Furthermore, this panel of 116 proteins was able to explain 40.0% of the variance in exercise induced changes in plasma HDL-C, while clinical predictors alone (including baseline HDL-C) explained only 3.9%. Pathway analysis of these 116 proteins identified several biological processes including pathways involved in the progression towards atherosclerosis, angiogenesis, mTOR signaling, and mitochondrial fatty acid synthesis. Conclusions: Circulating proteins may allow for prediction of exercise induced changes in HDL-C. Additionally, proteins predictive of HDL-C response to exercise are associated with important biological pathways and may provide insights into the molecular mechanisms of the benefits of regular exercise.

Targeting HDL in tumor microenvironment: New hope for cancer therapy.

Epidemiological studies have shown that plasma HDL-C levels are closely related to the risk of prostate cancer, breast cancer, and other malignancies. As one of the key carriers of cholesterol regulation, high-density lipoprotein (HDL) plays an important role in tumorigenesis and cancer development through anti-inflammation, antioxidation, immune-modulation, and mediating cholesterol transportation in cancer cells and noncancer cells. In addition, the occurrence and progression of cancer are closely related to the alteration of the tumor microenvironment (TME). Cancer cells synthesize and secrete a variety of cytokines and other factors to promote the reprogramming of surrounding cells and shape the microenvironment suitable for cancer survival. By analyzing the effect of HDL on the infiltrating immune cells in the TME, as well as the relationship between HDL and tumor-associated angiogenesis, it is suggested that a moderate increase in the level of HDL in vivo with consequent improvement of the function of HDL in the TME and induction of intracellular cholesterol efflux may be a promising strategy for cancer therapy.