Elevated High-density Lipoprotein Cholesterol Research Articles

Abstract 676: Novel Human Variants Of SR-B1 Impact HDL-cholesterol Clearance

The reverse cholesterol transport (RCT) pathway is the primary avenue by which our bodies lower plasma cholesterol levels. In RCT, peripheral cholesterol is transported by high density lipoproteins (HDL) to the liver for excretion. Cholesterol delivery is facilitated by a high-affinity interaction between HDL and its receptor, scavenger receptor class B member 1 (SR-B1). Recently, novel variants within the gene encoding SR-B1 were identified in a population of Icelandic people. Four missense mutations - V32M-, V111M-, V135I-, and G319V-SR-B1- were associated with elevations in plasma HDL-cholesterol. Based on these clinical phenotypes, we hypothesized that these conserved variants of SR-B1 would disrupt HDL-cholesterol transport. To assess the functions of the variants, we transiently transfected vector, wild-type, or mutant SR-B1 constructs into COS7 cells which express low endogenous SR-B1. All mutants displayed decreased DiI-HDL binding, yet only G319V-SR-B1 displayed a significant decrease in DiI lipid uptake, by 42% compared to wild-type. SR-B1 also mediates cholesterol efflux from cells into HDL. When assayed, only V32M- and G319V-SR-B1 decreased cholesterol efflux to HDL by 25 and 52%, respectively, compared to wild-type. Additionally, we demonstrated a decrease in total and cell surface expression of the G319V-SR-B1 variant compared to wild-type SR-B1, suggesting that impairments in function could be due to decreased expression. SR-B1 forms oligomers to facilitate its functions, and all variants maintained the ability to form higher order oligomers. To further characterize the SR-B1 variants, we utilized a recently-developed purification system to generate full-length SR-B1 protein and performed microscale thermophoresis to monitor changes in affinity for HDL. Paralleling our results from cellular assays, all SR-B1 variants displayed impaired HDL binding. When mapped to a homology model of full-length SR-B1, all four mutations are within the extracellular region, but the functional perturbations caused by each mutation warrants further studies. These mutants, combined with previously characterized SR-B1 variants, can be integrated as important pieces in the puzzle of cholesterol homeostasis and cardiovascular disease.

The Relationship Between Metabolic Syndrome and Benign Prostate Enlargement: A Case-Control Study in a Peruvian Military Hospital.

This study aimed to determine how metabolic syndrome is related to benign prostatic enlargement in males under 60 years old in a national military hospital in Peru. We conducted a retrospective, quantitative, case-control study. By simple random sampling, 87 cases with benign prostatic enlargement and 174 controls were included, with a statistical power of 80%. The benign prostatic enlargement was evaluated by clinical picture and ultrasound and the metabolic syndrome was evaluated according to the Adult Treatment Panel III criteria. The statistical analysis was performed using the STATAv14 program, the chi-square statistical test was used and odds ratio was obtained, at a significance level of 5%. The mean age of the cases and controls was 55 (51-58) and 52 (46-57), respectively. By multivariate analysis, the factors related to benign prostatic enlargement were the presence of benign prostatic enlargement (adjusted odds ratio: 2.71, 95% CI: 1.27-5.80; P=.010), waist circumference ≥102 cm (adjusted odds ratio: 6.51, 95% CI: 3.09-13.71; P < .001), elevated fasting glucose (adjusted odds ratio: 1.38, 95% CI: 0.65-2.91; P=.399), high triglycerides (adjusted odds ratio: 5.29, 95%: CI 2.40-11.64; P < .001), and arterial hypertension (adjusted odds ratio: 4.67, 95% CI 2.19-9.95; P < .001). Elevated high-density lipoprotein cholesterol was a protective factor (adjusted odds ratio: 0.09, 95% CI: 0.04-0.20; P < .001). The present study showed that metabolic syndrome and its components (waist circumference, hypertension, triglycerides, and high-density lipoprotein cholesterol) are factors related to benign prostatic enlargement in patients under 60 years old in a military hospital in Peruvian population. Waist circumference as an indicator of overweight/obesity is a practical anthropometric marker of interest in public health.

HDL - Quo vadis

Many epidemiological studies found low plasma levels of high-density lipoprotein (HDL) cholesterol (HDL-C) associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles show many anti-atherogenic actions. However, until now, clinical trials did not find any prevention of ASCVD events by drugs elevating HDL-C levels, at least not beyond statins. Also, genetic studies show no associations of HDL-C levels altering variants with cardiovascular risk. Therefore, the causal role and clinical benefit of HDL-C elevation in ASCVD are questioned. However, the interpretation of previous data has important limitations: First, the inverse relationship of HDL-C with the risk of ASCVD is limited to concentrations < 60 mg/dl (< 1.5 mmol/l). Higher concentrations do not reduce the risk of ASCVD events and are even associated with increased mortality. Therefore, neither the higher-the-better strategies of earlier drug developments nor the assumption of linear cause-and-effect relationships in Mendelian randomization trials are justified. Second, most of the drugs tested so far do not act specifically on HDL metabolism. Therefore, the futile endpoint studies question the clinical benefit of the investigated drugs, but not the importance of HDL in ASCVD. Third, the vascular functions of HDL are not exerted by its cholesterol content (i.e. HDL-C), but by a variety of other molecules. Comprehensive knowledge of the structure-function-disease relationships of HDL particles and their molecules is a prerequisite for testing their physiological and pathogenic relevance and possibly for optimizing the diagnosis and treatment of persons with HDL-associated risk of ASCVD, but also for other diseases, such as diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy

Ethnopharmacological relevanceThe capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. Aim of the studyThe study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. Materials and methodsBiochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. ResultsWe confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. ConclusionsOur study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia.

Hypocholesterolaemia is associated with elevated cancer risk and mortality, yet the relation between chronic lymphocytic leukaemia (CLL) and serum lipid profile remains unclear. Our study aims to evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram that incorporates lipid metabolism. We enrolled 761 newly diagnosed CLL patients and separated them into either derivation (n = 507) or validation (n = 254) cohorts. The prognostic nomogram was constructed through multivariate Cox regression analyses, with performance evaluated using C-index, the area under the curve, calibration, and decision curve analyses. Decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at diagnosis were significantly associated with worse time to first treatment (TTFT) and cancer-specific survival (CSS), and simultaneously, low HDL-C with low LDL-C was identified as an independent prognostic indicator for both TTFT and CSS. CLL patients achieving complete or partial remission post-chemotherapy had significantly increased TC, HDL-C, and LDL-C levels compared with the baseline, and post-therapeutic HDL-C and LDL-C elevation correlated with favourable survival. The prognostic nomogram augmenting the CLL international prognostic index with low cholesterol levels yielded higher predictive accuracy and discrimination capacity for both 3-year and 5-year CSS. In conclusion, cholesterol profiles can be used as a cheap and readily accessible tool for predicting prognosis in CLL practice.

San-wei-tan-xiang capsule attenuates atherosclerosis by increasing lysosomal activity in adipose tissue macrophages

Ethnopharmacological relevanceDyslipidemia is the leading risk factor of atherosclerosis (AS). Adipose tissue macrophages (ATMs) can regulate postprandial cholesterol levels via uptake and hydrolyzation of lipids and regulation of macrophage cholesterol efflux (MCE). San-wei-tan-xiang (SWTX) capsule, a Traditional Chinese medicine, exerts clinical benefits in patients with atherosclerotic cardiovascular diseases. Aim of the studyThis work is aimed to evaluate the chemical ingredients and mechanisms of SWTX in anti-AS. Materials and methodsThe chemical ingredients of SWTX identified by liquid chromatography coupled with tandem mass spectrometry were used for network pharmacological analysis. The atheroprotective function of SWTX was evaluated in ApoE−/− mice fed a cholesterol-enriched diet. ResultsThe chemical ingredients identified in SWTX were predicated to be important for lipid metabolism and AS. Animals studies suggested that SWTX effectively attenuated the atherosclerotic plaque growth, elevated postprandial HDL cholesterol levels, elevated the proportion of Tim4 and CD36-expressed ATMs, and upregulated the uptake of lipid and lysosomal activity in ATMs. SWTX-induced elevation of postprandial HDL cholesterol levels was dependent on increased lysosomal activity, since chloroquine, an inhibitor of lysosomal function, blocked the effect of SWTX. Lastly, some predicated bioactive compounds in SWTX can elevate lysosomal activity in vitro. ConclusionSWTX could attenuate atherosclerotic plaque formation by elevating lysosomal activity and enhancing MCE in ATMs.

Dyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study.

Preeclampsia is a leading cause of maternal morbidity, and dyslipidemia has been associated with preeclampsia in observational studies. We use Mendelian randomization analyses to estimate the association between lipid levels, their pharmacological targets, and the risk of preeclampsia in 4 ancestry groups. We extracted uncorrelated (R2<0.001) single-nucleotide polymorphisms strongly associated (P<5×10-8) with LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), and triglycerides from genome-wide association studies of European, admixed African, Latino, and East Asian ancestry participants. Genetic associations with risk of preeclampsia were extracted from studies of the same ancestry groups. Inverse-variance weighted analyses were performed separately for each ancestry group before they were meta-analyzed. Sensitivity analyses were conducted to evaluate bias due to genetic pleiotropy, demography, and indirect genetic effects. The meta-analysis across 4 ancestry groups included 1.5 million subjects with lipid measurements, 7425 subjects with preeclampsia, and 239 290 without preeclampsia. Increasing HDL-C was associated with reduced risk of preeclampsia (odds ratio, 0.84 [95% CI, 0.74-0.94]; P=0.004; per SD increase in HDL-C), which was consistent across sensitivity analyses. We also observed cholesteryl ester transfer protein inhibition-a drug target that increases HDL-C-may have a protective effect. We observed no consistent effect of LDL-C or triglycerides on the risk of preeclampsia. We observed a protective effect of elevated HDL-C on risk of preeclampsia. Our findings align with the lack of effect in trials of LDL-C modifying drugs but suggest that HDL-C may be a new target for screening and intervention.

Review of Inflammatory Markers in Metabolic Syndrome

The conditions included in the definition of metabolic syndrome typically include central obesity (excessive fat accumulation around the waist), insulin resistance, hyperglycemia (elevated blood sugar levels), dyslipidemia (abnormal levels of lipids in the blood), and hypertension (high blood pressure). Having any three or more of these conditions is considered to be indicative of metabolic syndrome. Metabolic syndrome (MetS) is emerging as a major public health problem with pro-inflammatory changes leading to Insulin Resistance and Cardiovascular Disease (CVD) at a very young age. Metabolic syndrome (MetS) is a global health concern; metabolic syndrome is becoming more common in our country. It is found to be a risk factor for insulin resistance and abnormal adipose tissue . Clinical symptoms of the syndrome could include abdominal obesity, hypertension, diabetes, hypertriglyceridemia, and low HDL cholesterol. So far various studies have been conducted on the effect of inflammatory markers like Serum Uric acid (UA), serum homocysteine, Leptin, Lp(a) etc. Most of them have reported a positive correlation between these inflammatory markers and the various components of (MetS) like abdominal obesity, elevated Blood pressure, Fasting blood Glucose and Lipid profile abnormalities like elevated Triglycerides (TAG) and low High Density Lipoprotein-Cholesterol (HDL-C). Various studies have reported a positive correlation between serum uric acid and Serum Homocysteine and Lp(a) in causing endothelial dysfunction and premature Cardiovascular events. Hence a review of the studies pertaining to the various inflammatory markers was done. There was an association of various inflammatory markers like uric acid, homocysteine, MDA, lipoprotein and others. More awareness must be created even at the high school level regarding the ill effects of sedentary lifestyle the likely hood of metabolic syndrome. An early identification of surging biomarker levels in high-risk children may find new cases at an earlier stage to prevent upcoming diabetes mellitus and its complications.

Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345000 men and women aged 20-79 years.

Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. A total of 344 556 individuals (20-79 years, 52 % women) recruited from population-based health screening during 1985-2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >99 mg/dl (< 0.78, 0.78-1.01, 1.04-1.27, 1.30-1.53, 1.55-1.79, 1.81-2.04, 2.07-2.31, 2.33-2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. During a mean follow-up of 22 years, 69505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50-59 mg/dl (1.30-1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21-1.43), 1.05 (0.89-1.24), 1.26 (1.09-1.46) and 1.68 (1.48-1.90) for all-cause, CVD, cancer and non-CVD/non-cancer mortality, respectively. For HDL-C levels <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes. Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL.

Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-aged women need to be determined. The current study was designed to compare the changes in HDL quantity and quality among middle-aged women depending on exercise intensity, frequency, and duration; participants were divided into a sedentary group (group 1), a middle-intensity group (group 2), and a high-intensity group (group 3). There were no differences in anthropometric parameters among the groups, including blood pressure, muscle mass, and handgrip strength. Although there was no difference in serum total cholesterol (TC) among the groups, the serum HDL-C and apolipoprotein (apo)A-I levels remarkably increased to 17% and 12%, respectively, in group 3. Serum low-density lipoprotein-cholesterol (LDL-C), glucose, triglyceride, and the apo-B/apoA-I ratio were remarkably decreased in the exercise groups depending on the exercise intensity; group 3 showed 13%, 10%, and 45% lower LDL-C, glucose, and triglyceride (TG), respectively, than group 1. The hepatic and muscle damage parameter, aspartate aminotransferase (AST), was significantly decreased in the exercise groups, but high-sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) were similar in the three groups. In LDL, the particle size was increased 1.5-fold (p &lt; 0.001), and the oxidation extent was decreased by 40% with a 23% lower TG content in group 3 than in group 1. In the exercise groups (groups 2 and 3), LDL showed the slowest electromobility with a distinct band intensity compared to the sedentary group (group 1). In HDL2, the particle size was 2.1-fold increased (p &lt; 0.001) in the exercise group (group 3) with a 1.5-fold increase in TC content compared to that in group 1, as well as significantly enhanced antioxidant abilities, paraoxonase (PON) activity, and ferric ion reduction ability (FRA). In HDL3, the particle size was increased 1.2-fold with a 45% reduction in TG in group 3 compared to group 1. With increasing exercise intensity, apoA-I expression was increased in HDL2 and HDL3, and PON activity and FRA were enhanced (p &lt; 0.001). In conclusion, regular exercise in middle-aged women is associated with the elevation of serum HDL-C and apoA-I with the enhancement of HDL quality and functionality and an increase in the TC content, particle size, and antioxidant abilities. With the reduction in TG and oxidized products in LDL and HDL, lipoproteins could have more anti-atherogenic properties through regular exercise in an intensity-dependent manner.

PS-BPB05-1: DUAL DISRUPTION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE AND APOE GENE ACCELERATES KIDNEY FIBROSIS AND AGING AFTER INJURY

Objective: Advances in medical science have made it possible to control diseases such as cancer, autoimmune diseases, and infectious diseases, extending the lifespan of affected people around the world. On the other hand, the number of patients with Chronic Kidney Disease (CKD) is increasing worldwide, and hypertension is a key factor. Suppression of CKD is important for extending healthy life expectancy. In this study, we will clarify the effects of the interaction between hypertension and atherosclerosis on renal fibrosis and aging. Design and method: Wild type (WT) mouse, apolipoprotein E-/- (ApoE KO) mouse, and endothelial nitric oxide synthase (eNOS)-/- ; ApoE-/- (DKO) mouse were obtained by crossing eNOS+/- mouse and ApoE+/- mouse. Unilateral ureteral obstruction (UUO) was performed on 8–10 weeks old male mice after blood pressure and lipid profile were measured. Mice were sacrificed 10 days after UUO. The degree of renal tubular injury, fibrosis and kidney senescence were evaluated. Results: DKO mice exhibited the most pronounced blood pressure and lipid abnormalities among the three groups, with a significant elevation of blood pressure, total cholesterol, and low HDL cholesterol compared to WT mice. DKO mice manifested elevated blood pressure, higher total cholesterol and lower HDL than WT mice. Compared with WT mice, ApoE KO and DKO mice showed sustained kidney injury molecule-1 expression and kidney fibrosis was significantly higher in ApoEKO and DKO mice. mRNA expression of genes related to kidney fibrosis was the highest in DKO mice. The mRNA expression of Zinc alpha2 Glycoprotein and heme oxygenase-1 were significantly decreased in DKO mice. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO mice, with DKO mice being the highest. Senescence associated beta-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin autophagy spatial coupling compartments (TASCCs, Sci Transl Med. 2019;11(476):eaav4754. J Clin Invest. 2019;129(11):4797- 4816.) formation was found in DKO mice. Conclusion: Mice at high risk for cardiovascular disease developed kidney fibrosis and aging even in the young mice after injury. Vulnerability to oxidative stress due to endothelial cell dysfunction promotes fibrosis and aging. Managing lifestyle-related diseases including hypertension from a young age is important for CKD prevention.

Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet.

Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia.

Epigenetic Age Acceleration in Mothers and Offspring 4-10 Years after a Pregnancy Complicated by Gestational Diabetes and Obesity.

A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4−10 years before study enrollment were included. Clinical data and whole blood samples were collected and quantified to obtain DNA methylation (DNAm) estimates using the Illumina MethylEPIC 850K array in mothers and offspring. DNAm age and age acceleration were evaluated using the Horvath and Hannum clocks. Multivariable linear regression models were performed to determine the association between EAA and leptin, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, and HOMA-IR. Mothers with a GDM and non-GDM pregnancy had strong correlations between chronological age and DNAm age (r > 0.70). Offspring of GDM mothers had moderate to strong correlations, whereas offspring of non-GDM mothers had moderate correlations between chronological age and DNAm age. Association analyses revealed a significant association between EAA and fasting insulin in offspring (FDR < 0.05), while HDL-C was the only metabolic marker significantly associated with EAA in mothers (FDR < 0.05). Mothers in the GDM group had a higher predicted epigenetic age and age acceleration than mothers in the non-GDM group. The association between EAA with elevated fasting insulin in offspring and elevated HDL-C in mothers suggests possible biomarkers that can better elucidate the effects of exposure to a GDM pregnancy and future cardiometabolic outcomes.

U-shaped relationship between apolipoprotein A1 levels and mortality risk in men and women.

Apolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels. To investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis. A prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively. In 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91-2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07-1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07-1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67-1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality. Both very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.

Association of Short-Term Exposure to PM2.5 with Blood Lipids and the Modification Effects of Insulin Resistance: A Panel Study in Wuhan.

Results of previous studies about the acute effects of fine particulate matter (PM2.5) on blood lipids were inconsistent. This study aimed to quantify the short-term effects of PM2.5 on blood lipids and estimate the modifying role of insulin resistance, reflected by the homeostasis model assessment of insulin resistance (HOMA-IR). From September 2019 to January 2020, the study recruited 70 healthy adults from Wuhan University for a total of eight repeated data collections. At each visit, three consecutive days were monitored for personal exposure to PM2.5, and then a physical examination was carried out on the fourth day. The linear mixed-effect models were operated to investigate the impact of PM2.5 over diverse exposure windows on blood lipids. With the median of the HOMA-IR 1.820 as the cut-off point, participants were assigned to two groups for the interaction analyses. We found the overall mean level (standard deviation, SD) of PM2.5 was 38.34 (18.33) μg/m3. Additionally, with a 10 μg/m3 rise in PM2.5, the corresponding largest responses in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), as well as high-density lipoprotein cholesterol (HDL-C), were -0.91% (95% confidence interval (CI): -1.63%, -0.18%), -0.33% (95% CI: -0.64%, -0.01%,), -0.94% (95% CI: -1.53%, -0.35%), and 0.67% (95% CI: 0.32%, 1.02%), respectively. The interaction analyses revealed that a significantly greater reduction in the four lipids corresponded to PM2.5 exposure when in the group with the lower HOMA-IR (&lt;1.820). In conclusion, short-term PM2.5 exposure over specific time windows among healthy adults was associated with reduced TG, TC, as well as LDL-C levels, and elevated HDL-C. Additionally, the association of PM2.5-lipids may be modulated by insulin resistance.

EFEITO DO EXERCÍCIO AERÓBICO SOBRE A FUNÇÃO MOTORA DOS MEMBROS EM PACIENTES DIABÉTICOS

ABSTRACT Introduction: Gestational Diabetes is a group of metabolic disorders that result in glucose intolerance during pregnancy. Among the range of treatments are diet, continuous use of medication, and psychological monitoring. Since it is a multidisciplinary treatment, a proper protocol is vital for a favorable outcome. In addition, there are questions about the benefits of physical activity as a complementary therapy. Objective: To verify the impact of adding exercise to the hospital protocol for patients with gestational diabetes, both on the risks of type 2 diabetes in pregnant women and on the obesity of their offspring. Methods: Sixty pregnant women diagnosed with Gestational Diabetes were randomly divided into control and intervention groups. Both groups received specific treatment and intervention, and the experimental group practiced controlled moderate-intensity physical activity (125-146bpm). Morning blood samples were collected from both groups to check fasting glucose and insulin levels, indicators of lipid metabolism, low and high-density lipoprotein cholesterol, apolipoprotein B. The Brog scale measured the fatigue level. In addition, the premature rupture of membranes, postpartum hemorrhage, neonatal asphyxia, macrosomia, and others was checked. Results: The peripheral blood total cholesterol levels were 5.93, 5. 38, low-density lipoprotein cholesterol levels were 2.95 before versus 2.64 after, and apolipoprotein B levels were 1.84 versus 1.59 in the control group, high-density lipoprotein cholesterol content increased from 1.74 to 1.88, blood cholesterol, and apolipoprotein B levels after the intervention in the experimental group were lower than those in the control group, with an elevation of high-density lipoprotein cholesterol. Conclusion: Aerobic exercise proved to be more appropriate for patients with gestational diabetes in the later stages of pregnancy and may also be adapted for bedridden patients refractory to traditional drugs. Evidence Level II; Therapeutic Studies - Investigating the result.

Clinical, Nutritional, and Functional Evaluation of Chia Seed-Fortified Muffins.

Health-protective functional foods are gaining popularity in the world of nutrition because they promote excellent health while decreasing pharmaceutical burdens. Chia seeds (CS) (Salvia hispanica L.), the greatest vegetative source of α-linolenic acid, bioactive proteins, and fibers, are among the top unconventional oilseeds shown to have bounteous benefits against various non-communicable diseases. Purposely, this study was designed to integrate roasted CS powder into white-flour-based ordinary bakery goods to improve their nutritional and nutraceutical profiles. CS efficacy in normal and hyperlipidemic Sprague-Dawley rats resulted in mitigating blood glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol while elevating high-density lipoprotein cholesterol, hematocrit, hemoglobin, red blood cell counts, and platelets. The nutritional profiling of chia-fortified muffins indicated significant increases of 47% in fat, 92% in fiber, 15% in protein, and 62% in minerals. The farinographic experiments of CS-blends revealed generally improved dough quality features with a significant rise in the degree of softening as fortification levels increased. A marketable recipe for CSF-muffins with several degrees of fortification demonstrated a significant rise in fat, 92% rise in fiber, 15% rise in protein, and 62% rise in minerals. Sensorial evaluation by trained taste panelists revealed a maximum appraisal of the 15% chia-fortified muffins due to aroma, appearance, and overall acceptability, and were forwarded for being acceptable for commercialization.

Traditional Chinese Medicine Formula Jian Pi Tiao Gan Yin Reduces Obesity in Mice by Modulating the Gut Microbiota and Fecal Metabolism.

The current study employed the high-fat diet (HFD) induced murine model to assess the relationship between the effect of Jian Pi Tiao Gan Yin (JPTGY) and the alterations of gut microbiota and fecal metabolism. C57BL/6 mice were used to establish an animal model of obesity via HFD induce. Serum biochemical indicators of lipid metabolism were used to evaluate the pharmacodynamics of JPTGY in obese mice. Bacterial communities and metabolites in the feces specimens from the controls, the Group HFD, and the JPTGY-exposed corpulency group were studied by 16s rDNA genetic sequence in combination with liquid chromatography-mass spectrometry (LC-MS) based untargeted fecal metabolomics techniques. Results revealed that JPTGY significantly decreased the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and elevated high-density lipoprotein cholesterol (HDL-C). Moreover, JPTGY could up-regulate the abundance and diversity of fecal microbiota, which was characterized by the higher phylum of proteobacteria. Consistently, at the genus levels, JPTGY supplementation induced enrichments in Lachnospiraceae NK4A136 group, Oscillibacter, Turicibacter, Clostridium sensu stricto 1, and Intestinimonas, which were intimately related to 14 pivotal fecal metabolins in respond to JPTGY therapy were determined. What is more, metabolomics further analyses show that the therapeutic effect of JPTGY for obesity involves linoleic acid (LA) metabolism paths, alpha-linolenic acid (ALA) metabolism paths, glycerophospholipid metabolism paths, arachidonic acid (AA) metabolism paths, and pyrimidine metabolism paths, which implied the potential mechanism of JPTGY in treating obesity. It was concluded that the linking of corpulency phenotypes with intestinal flora and fecal metabolins unveils the latent causal link of JPTGY in the treatment of hyperlipidemia and obesity.

IMPACT OF PLASMA HDL CHOLESTEROL LEVELS, MEASURED ONE YEAR BEFORE ACUTE MYOCARDIAL INFARCTION, ON MORTALITY AFTER THE ACUTE EVENT

Introduction: Although epidemiological studies demonstrated that HDL cholesterol (HDL-C) levels are associated with higher cardiovascular risk, pharmacological interventions for elevated HDL-C levels have failed to show a risk reduction. Objective: To evaluate patients admitted for acute myocardial infarction (AMI) to determine whether HDL-C levels measured up to 1 year before the event have an impact on post-event mortality. Methods: A retrospective cohort study was conducted using data from the database of the Curitiba (Brazil) city hall. This study included 1,363 patients hospitalized from 2008 to 2015, with a diagnosis of infarction and available HDL-C values measured up to 1 year before the coronary event. The mean HDL-C levels obtained in this period and at 6 and 12 months after discharge were correlated with hospital mortality. Results: HDL-C levels of ≤35 mg/dL resulted in lower mortality than values of ≥50 mg/dL. This indicates that the mortality risk of patients with HDL-C levels of ≥50 mg/dL was 30% higher than ≤35 mg/dL, regardless the age and the total follow up. The survival rate at 6 and 12 months of follow-up for patients with HDL-C levels of ≥50 mg/dL was reduced in relation to other quartiles, with higher evidence of mortality at 12 months. Conclusions: The patients with higher HDL-C levels in the year preceding an AMI presented worse prognosis than those with lower HDL-C levels after the acute event. This reinforces the paradoxical effect of HDL-C on cardiovascular risk and the results of recent intervention studies.

Phycochemical and Biological Activities From Different Extracts of Padina antillarum (Kützing) Piccone.

Seaweeds are non-vascular, photosynthetic that inhabit the coastal regions commonly within rocky intertidal or submerged reef-like habitats and have been one of the richest and most promising sources of bioactive primary and secondary metabolites with antimicrobial properties. They selectively absorb elements like Na, K, Ca, Mg, I, and Br from the seawater and accumulate them in their thalli. Padina antillarum (Kützing) Piccone is a member of Phaeophycota and has remarkable phycochemistry as well as bioactivity. The phycochemical tests of the different extracts showed the presence of alkaloids, terpenoids, saponins, tannins, steroids, and phenols. The relative percentage of Oxirane, tetradecyl (C16H32O), and Cyclononasiloxane (C18H54O9Si9) are higher while Tetrasiloxane (C16H50O7Si8) is lowest in Gas Chromatography – Mass Spectrometry analysis. FRAP, %inhibition, the total antioxidant value of P. antillarum was higher in methanolic extract. Hexane, chloroform extracts showed no zone of inhibition against Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Staphylococcus epidermidis. The methanolic extract of P. antillarum exhibits a maximum zone of inhibition against S. epidermidis (18.66 ± 0.09). Antifungal activity of the P. antillarum in hexane extract exhibited no zone of inhibition against Aspergillus niger and Penicillium notatum while the chloroform extract yields maximum zone (37 ± 0.012, 21.66 ± 0.03). Diabetes mellitus is one of the most familiar chronic diseases associated with carbohydrate metabolism. It is also an indication of co-morbidities such as obesity, hypertension, and hyperlipidemia which are metabolic complications of both clinical and experimental diabetes. The treatment of P. antillarum methanol extract in mice reduced the body weight loss, low level of triglycerides, and elevated HDL cholesterol level as compared to diabetic mice.