Serum Low-density Lipoprotein Cholesterol Research Articles

Missing Regulation Between Genetic Association and Transcriptional Abundance for Hypercholesterolemia Genes

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels. One hypothesis is that genetically mediated variation in transcript abundance, detected via the analysis of expressed quantitative trait loci (eQTLs), is key to the biologic function of causal variants. Here, we investigate the hypothesis that non-coding GWAS risk variants affect the homeostatic expression of a nearby putatively causal gene for serum LDL-C levels. Methods: We establish a set of twenty-one expert-curated and validated genes implicated in hypercholesterolemia via dose-dependent pharmacologic modulation in human adults, for which the relevant tissue type has been established. We show that the expression of these LDL-C genes is impacted by eQTLs in relevant tissues and that there are significant genomic-risk loci in LDL-GWAS near these causal genes. We evaluate, using statistical colocalization, whether a single variant or set of variants in each genetic locus is responsible for the GWAS and eQTL signals. Results: Genome-wide association study results for serum LDL-C levels demonstrate that the 402 identified genomic-risk loci for LDL-C are highly enriched for known causal genes for LDL-C (OR 527, 95% CI 126–5376, p < 2.2 × 10−16). However, we find limited evidence for colocalization between GWAS signals near validated hypercholesterolemia genes and eQTLs in relevant tissues (colocalization rate of 26% at a locus-level colocalization probability > 50%). Conclusions: Our results highlight the complexity of genetic regulatory effects for causal hypercholesterolemia genes; we suggest that context-responsive eQTLs may explain the effects of non-coding GWAS hits that do not overlap with standard eQTLs.

Fermented Cassava Residue Meal Improves Meat Quality by Regulating Muscle Fiber and Enhancing Lipid Metabolism in Huanjiang Mini-Pigs

This research investigated the effects of cassava residue meal (CRM) and fermented CRM (FCRM) on the growth performance, serum lipid indicators, carcass traits, and meat quality of Huanjiang mini-pigs. One hundred twenty Huanjiang mini-pigs with similar BW (body weight, 8.85 ± 0.64 kg) were divided into three dietary treatment groups: the CON group with a basal diet; the CRM group with a diet containing 5% CRM; and the FCRM group with a diet containing 5% FCRM. The feeding trial was conducted for 30 days. The findings revealed that dietary CRM and FCRM did not influence the growth performance and diarrhea rate of Huanjiang mini-pigs (p > 0.05). Dietary FCRM supplementation increased serum total cholesterol level compared to the CON group while decreasing serum cholinesterase level compared to the CON and CRM groups (p < 0.05). The level of serum low-density lipoprotein-cholesterol was higher (p < 0.05) in the CRM and FCRM groups in regard to the CON group. In addition, CRM and FCRM supplementation reduced (p < 0.05) the backfat thickness and carcass yield of Huanjiang mini-pigs. The meat quality analysis showed that dietary CRM and FCRM improved the meat quality by increasing the intramuscular fat content and redness (a*) value and decreasing the lightness (L*) value. Moreover, the MyHC-IIx expression in the longissimus thoracis (LT) muscle was upregulated (p < 0.05) in the CRM group, while MYHC-IIb expression displayed an increasing trend (p = 0.076) in the FCRM group relative to the CON group. The fatty acid composition in the LT muscle also revealed that the C20:0 level was lower in the CRM and FCRM groups, while the ∑SFA and ∑SFA/∑UFA were reduced (p < 0.05) in the FCRM group relative to the CON group. In summary, dietary CRM and FCRM supplementation improved the meat quality of Huanjiang mini-pigs without affecting growth performance and diarrhea rate. Notably, FCRM exhibited better effects on meat quality than CRM.

Association of LDL-cholesterol with prognosis in patients admitted for acutely decompensated heart failure.

The association of low-density lipoprotein cholesterol (LDL-C) levels and prognosis in patients with heart failure (HF) remains uncertain. This study aimed to evaluate the prognostic significance of LDL-C in patients admitted for acutely decompensated HF and establish a safety cut-off value in this population. This retrospective, observational study included 167 consecutive patients admitted for acute HF. LDL-C levels were measured on hospital admission, and patients were categorized according to their estimated cardiovascular (CV) risk. The primary endpoint was all-cause mortality at 1-year, while secondary endpoints included HF hospitalizations, major thrombotic events, and net clinical benefit. During the follow-up period, 14.4% of patients died. Higher LDL-C levels were independently associated with improved survival, with a 4-fold increase in survival probability for each 1mg/dL increase in serum LDL-C. The minimum LDL-C value not associated with increased mortality risk was 88mg/dL. Patients with LDL-C below this cut-off had a significantly higher risk of mortality and a tendency for higher HF hospitalization risk. The net clinical benefit endpoint was also influenced by LDL-C levels, with LDL-C below 88mg/dL associated with an increased risk of events. In patients admitted for acutely decompensated HF, higher LDL-C levels were associated with reduced risk of mortality. An LDL-C value below 88m/dL was associated with increased mortality, suggesting the need for a more liberal LDL-C target in this specific patient population. These findings highlight the importance of considering LDL-C levels in the management and risk assessment of patients with HF.

High-selenium exposure is associated with modulation of serum lipid metabolism.

At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia.

Relationship between Heated Tobacco Product Use and Low-Density Lipoprotein Cholesterol in Korean Adults: A Cross-Sectional Study Using Korea National Health and Nutrition Examination Survey 2018-2021 (VII-1 and VIII).

The use of heated tobacco products (HTPs) among Korean adults has been steadily increasing since they were first introduced in 2017. It is known that smoking combustible cigarettes (CCs) adversely affects the serum lipid profile and increases the risk of cardiovascular disease. However, the health impacts of HTPs remain under- researched. This study, therefore, aims to explore the effects of HTP use on serum lipid levels. This study involved 10,309 participants, selected from the Korea National Health and Nutrition Examination Survey VII-1 and VIII conducted between 2018 and 2021. Participants were categorized based on their smoking status: "HTPs ever user" included dual, triple, and past HTP users; "current HTPs only user" for those exclusively using HTPs; "current CCs only user" for those exclusively smoking CCs; and "never smoker." Logistic regression analysis was used to assess the impact of smoking type on serum lipid concentrations. The analysis revealed that the "HTPs ever user" group had a higher odds ratio (OR) for elevated total cholesterol compared to the "never smoker" group (OR, 1.40; 95% confidence interval [CI], 1.03-1.92). The likelihood of having high low-density lipoprotein (LDL)-cholesterol was greatest in the "current HTPs only user" group when compared to "never smokers" (OR, 1.71; 95% CI, 1.01-2.89). The findings indicate that exclusive use of HTPs is linked to an increased level of serum LDL-cholesterol. Further longitudinal studies are necessary to fully determine the health risks associated with HTPs.

Holy Basil (Ocimum sanctum L.) Flower and Fenofibrate Improve Lipid Profiles in Rats with Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD): The Role of Choline Metabolism.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to choline metabolism. The present study investigated the effect of holy basil (Ocimum sanctum L.) flower water extract (OSLY) on MASLD with choline metabolism as an underlying mechanism. Rats with high-fat diet (HFD)-induced MASLD received 250-1000 mg/kg bw of OSLY, fenofibrate, or fenofibrate + 1000 mg/kg OSLY combination. Biochemical parameters, choline metabolites, and one-carbon gene transcription were analyzed. OSLY and fenofibrate independently reduced serum LDL cholesterol (p < 0.02), liver cholesterol (p < 0.001), and liver triglyceride levels (p < 0.001) in HFD-fed rats. Only OSLY reduced signs of liver injury and increased serum HDL. Fenofibrate influenced choline metabolism by decreasing liver glycerophosphocholine (GPC; p = 0.04), as well as increasing betaine (p < 0.001) and the betaine:choline ratio (p = 0.02) in HFD-fed rats. Fenofibrate (vs. HFD) increased the expression of one-carbon metabolism genes Mthfd1l, Pemt, Smpd3, and Chka (p < 0.04). The OSLY treatment decreased liver GPC (500 mg dose; p = 0.03) and increased Smpd3 expression (1000 mg dose; p = 0.04). OSLY and fenofibrate showed weak synergistic effects on lipid and choline metabolism. Collectively, OSLY and fenofibrate independently improve lipid profiles in MASLD rats. The benefits of fenofibrate are partially mediated by choline/one-carbon metabolism, while those of OSLY are not mediated by this pathway. Holy basil flower extract merits further development as an alternative medicine for MASLD.

Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner

BackgroundPulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.MethodsA high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.ResultsPC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.ConclusionThese findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.

Acupoint thread-embedding at fat layer for abdominal obesity: a randomized controlled trial

To observe the clinical efficacy of acupoint thread-embedding at fat layer for abdominal obesity and its effects on glucose and lipid metabolism. Ninety-six patients with abdominal obesity were randomly divided into an acupoint embedding group (48 cases, 3 cases dropped out) and a sham embedding group (48 cases, 3 cases dropped out). Both groups received lifestyle interventions as basic treatment. The acupoint embedding group underwent thread-embedding at Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), and bilateral Liangmen (ST 21), Fenglong (ST 40), and Pishu (BL 20), with the thread implanted in the fat layer. The sham embedding group followed the same acupoint selection and procedure but without catgut implantation. Both groups were treated once every two weeks for 12 weeks, for a total of six treatments. Waist circumference, body weight, body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were measured, and appetite was assessed using the visual analogue scale (VAS) before and after treatment and at 12 weeks after treatment completion (follow-up) in the two groups. Visceral fat area (VFA) and subcutaneous fat area (SFA) at abdomen were measured, and blood glucose and lipid metabolism markers, including fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) index, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), leptin, tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6), were also tested before and after treatment in the two groups. Clinical efficacy was evaluated two weeks after treatment completion. After treatment and at follow-up, the waist circumference, body weight, BMI, WHR, WHtR, and appetite VAS scores in the acupoint embedding group were decreased compared to those before treatment (P<0.01). In the sham embedding group, waist circumference, body weight, BMI, WHtR, and appetite VAS score were also reduced after treatment compared to those before treatment (P<0.01). Except for body weight after treatment, the acupoint embedding group showed lower waist circumference, body weight, BMI, WHR, and WHtR values after treatment and at follow-up compared to the sham embedding group (P<0.01, P<0.05). Additionally, the appetite VAS score in the acupoint embedding group was lower than that in the sham embedding group after treatment (P<0.01). Both groups showed a reduction in abdominal VFA and SFA after treatment compared to those before treatment (P<0.01, P<0.05). In the acupoint embedding group, serum FBG, FINS, HOMA-IR index, TC, TG, LDL-C, leptin, TNF-α, and IL-6 levels were decreased compared to those before treatment (P<0.01), while HDL-C level was increased (P<0.01). In the sham embedding group, serum FBG and HOMA-IR index were decreased compared to those before treatment (P<0.01, P<0.05). After treatment, the abdominal SFA in the acupoint embedding group was lower than that in the sham embedding group (P<0.01). Additionally, the acupoint embedding group had lower levels of serum FINS, HOMA-IR index, TC, LDL-C, leptin, TNF-α, and IL-6 compared to the sham embedding group (P<0.05, P<0.01). The total effective rate in the acupoint embedding group was 82.2% (37/45), which was significantly higher than 15.6% (7/45) in the sham embedding group (P<0.01). The acupoint catgut embedding at fat layer could effectively reduce the obesity severity in patients with abdominal obesity, decrease abdominal fat accumulation, suppress appetite, improve glucose and lipid metabolism, reduce inflammatory responses, and has a sustained effect.

Effect of Vitamin D Supplementation on Serum Lipid Profile in Patients With Cardiovascular Risk

Abstract Introduction Existing evidence suggests vitamin D may benefit serum lipid profiles and, thus, cardiovascular health. The present study aimed to evaluate the effect of oral daily vitamin D supplementation on lipid profile among patients with cardiovascular risk. Material and Methods A total of 154 patients were included in the study, aged over 18 years, with at least one cardiovascular risk factor. Blood samples were collected at baseline and a 6-month follow-up. About 100 patients received vitamin D supplements in addition to the statin treatment, and 54 benefited from oral vitamin D treatment only. Results The serum level of vitamin D showed a significant increase after 6 months of treatment: from a mean basal level of 18.5 ng/ml (± 9.0) to a mean level at 6 months of 43.1 ng/ml (± 9.5) – p&lt;0,0001. In the group treated only with vitamin D supplements, a significant improvement was observed in the total cholesterol and LDL cholesterol levels, even if the patients did not benefit from statin treatment. Among patients who also received statins, differences were observed in changes in serum LDL cholesterol, HDL cholesterol, and triglycerides, in that the decreases observed were more pronounced than those who received only vitamin supplementation D. Conclusion Vitamin D supplementation appeared to have a beneficial effect on lipid profile. Vitamin D supplementation may be useful in dyslipidemia patients at high risk of cardiovascular diseases.

Impact of Controlling Serum Low-Density Lipoprotein Cholesterol and Triglycerides on Long-Term Clinical Outcomes in Diabetic Patients Who Have Undergone Percutaneous Coronary Intervention.

We investigated whether patients with diabetes who had good control of both low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) would be associated with better long-term clinical outcomes after percutaneous coronary intervention (PCI). Using our PCI registry (Fu-Registry), the 1,006 cases with diabetes were divided into 4 groups: Group 1, LDL-C ≥100 mg/dL and TG ≥175 mg/dL; Group 2, LDL-C <100 mg/dL and TG ≥175 mg/dL; Group 3, LDL-C ≥100 mg/dL and TG <175 mg/dL; and Group 4, LDL-C <100 mg/dL and TG <175 mg/dL. The primary endpoint during the follow-up period (median follow up of 1,984 days) was defined as major adverse cardiac events (MACEs). Additionally, all coronary events were defined as a secondary endpoint. The incidence rates of MACEs were as follows: Group 1, 38%; Group 2, 26%; Group 3, 31%; and Group 4, 27% (P=0.074), and the rates tended to be higher in Group 1. All coronary events were as follows: Group 1, 66%; Group 2, 56%; Group 3, 58%; and Group 4, 51% (P=0.032). In patients with diabetes who underwent PCI, the LDL-C and TG levels in Group 4 met secondary prevention targets for coronary artery disease and these patients showed better long-term clinical outcomes compared with those in other groups.

Characterization of tea polysaccharides from Tieguanyin oolong tea and their hepatoprotective effects via AMP-activated protein kinase-mediated signaling pathways.

In the present study, we succeeded in extracting tea polysaccharide (TPS) from Tieguanyin oolong tea, and the TPS was characterized. TPS is an acidic heteropolysaccharide containing rhamnose, arabinose, galactose, glucose (Glc), xylose, mannose, galacturonic acid, and guluronic acid. We found that TPS supplementation partially reversed the elevated levels of serum alanine aminotransferase, total cholesterol, and low-density lipoprotein cholesterol in high-fat diet (HD)-induced nonalcoholic fatty liver disease (NAFLD) mice (p<0.05), and hepatic steatosis and impaired Glc tolerance were also ameliorated. After HD intervention, the activity of Adenosine 5'-monophosphate-activated protein kinase (AMPK) and its downstream genes, including Sirtuin 1 (SIRT1), sterol regulatory element-binding protein-1c (SREBP1c), acetyl-coenzyme A carboxylase 1 (ACC1), and adipose triglyceride lipase (ATGL), was significantly inhibited (p<0.05). TPS can increase the expression of these genes. The hepatoprotective effects of TPS in AMPK-/- mice almost completely disappeared. Moreover, the expression levels of SIRT1, SREBP1c, ACC1, and ATGL did not significantly change after TPS supplementation (p>0.05). Therefore, our findings suggest that TPS protects the liver from hepatic glucolipid metabolism disorders in HD-induced NAFLD mice by activating AMPK-mediated signaling pathways.

Effect of synbiotic supplementation on obesity and gut microbiota in obese adults: a double-blind randomized controlled trial.

Synbiotics, combining specific probiotics and selected prebiotics, may benefit health issues like obesity, but evidence remains inconsistent. This study aimed to verify the effect of a pre-screened synbiotics combination [containing Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup), galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS)] on obesity in the population. In a randomized, double-blind, placebo-controlled trial, 80 individuals with obesity consumed daily synbiotics (containing MN-Gup 1 × 1011 CFU/day, GOS 0.7 g/day, and XOS 0.7 g/day) or placebo for 12 weeks. Body composition, blood lipids, serum hormone, bile acids, and gut microbiota were measured pre-and post-intervention. Synbiotics supplementation significantly decreased body fat percentage, waist, and serum low-density lipoprotein cholesterol (LDL-C), increased peptide YY, cholecystokinin, oxyntomodulin, GSH (glutathione peroxidase) in individuals with obesity. Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria and bile acids chenodeoxycholic acid (CDCA). Bifidobacterium and Romboutsia were significantly positively correlated with CDCA. A more favorable effect was observed in individuals with obesity and abnormal LDL-C compared to those without dyslipidemia. Twelve-week synbiotics intervention reduced body fat percentage, waist, and serum LDL-C, especially in individuals with obesity and abnormal LDL-C. The possible mechanisms may be related to changes in gut microbiota, bile acids and gut hormones. Chictr.org.cn, identifier ChiCTR2200064156.

Long-Term Propolis Intake-Induced Liver Lipid Remodeling in Mice: Effects on Phospholipid-to-Glycerolipid Metabolism and Free Fatty Acid-Mediated Thermogenesis.

Research on the patterns and mechanisms of liver lipid remodeling regulated by propolis is limited. In the present study, the nine-month experimental duration has shed light on the positive influences of propolis on lipid metabolism and thermogenesis capacity in the livers of mice. Eight major compounds in propolis were characterized using UPLC-QTOF-MS technology. Propolis significantly lowered serum triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C), but it also led to increased insulin (INS) levels. Lipidomics change trend analysis of 1671 lipid components across 42 categories revealed that the level of glycerophospholipids (GPs) decreased while glycerolipids (GLs) and fatty acids (FAs) increased in the liver. The expression levels of eight key genes involved in the conversion of GP to GL pathways in the liver were enhanced in the propolis group. Molecular docking results elucidated the high binding affinities between the eight components of propolis and eight receptors involved in lipid metabolism, indicating that primary compounds of propolis possess potent capabilities for phospholipid remodeling and lipolysis. These results imply that propolis could facilitate the browning of the liver adipose tissue, promote the conversion of GPs to DGs and FFAs, enhance the consumption of FFAs through thermogenic pathways, and thereby exert lipolytic and hepatoprotective functions.

Interplay between lipid profile and anthropometric measures as indicators of cardiometabolic risk in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with cardiometabolic risk factors. Women with PCOS have a two-fold increased risk of developing type 2 diabetes and substantially elevated risk for cardiovascular disease (CVD) events later in life. PCOS patients may require more comprehensive metabolic screening to identify populations at higher risk of developing CVD and dyslipidemia. It is recommended to evaluate lipid profile, glucose tolerance and of women with PCOS every 2-3 years. Simple, short, and easy methods for the assessment of CVD risk in women with PCOS may be useful tools for implementing CVD prevention strategies by doctors or nutritionists. The aim of this study was to investigate the usefulness of anthropometric indices in the assessment of cardiometabolic risk based on lipid profile in patients with PCOS. The study involved 49 of Caucasian women aged 18-39 who were diagnosed with PCOS based on the Rotterdam criteria and divided into two groups with normal lipid profile (N=14) and dyslipidemia (N=35). Biochemical parameters were tested in the morning while fasting. Anthropometric parameters such as Body Mass Index (BMI), Body Adiposity Index (BAI), Waist-to-Hip Ratio (WHR), and Waist-to-Height Ratio (WHtR) were calculated, while the Percent of Body Fat was measured using a body analyzer. The study demonstrated that women with dyslipidemia were older than the control group, 33 years (27-37) vs 24 years (21-26), p<0.01. Neither BMI nor BAI (%) correlated with total cholesterol (p=0.63 and p=0.27). Other lipid parameters, such as serum HDL cholesterol (R=-0.68, p<0.01; R=-0.58, p<0.01), LDL cholesterol (R=0.34, p=0.02; R=0.37, p=0.01), non-HDL cholesterol (R=0.40, p<0.01; R=0.42, p<0.01), and triglycerides (R=0.56, p<0.01; R=0.51, p<0.01) correlated with BMI and BAI (%). ROC analysis demonstrated a high predictive value for age in identifying dyslipidemia. ROC analysis demonstrated poor predictive value for BMI, BAI, WHR, WHtR in identifying dyslipidemia. Analysis of simple and rapid parameters used to assess body fat, such as BMI, BAI, WHR, and WHtR, has shown that they are poor predictors of dyslipidemia in women with PCOS. In young women with PCOS, age appears to be a more reliable predictor of dyslipidemia.

Lactobacillus johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids

Aim: Strains with high bile salt hydrolase (BSH) activity have the potential to regulate cholesterol metabolism. This study aimed to assess the alleviating effect of Lactobacillus johnsonii (L. johnsonii ) CCFM1376, a strain with high BSH activity, on mice with hypercholesterolemia and explore the mechanism of its effect through the modulation of bile acid metabolism. Methods: The BSH activity was measured using the ninhydrin method. C57BL/6J mice were given a high-cholesterol diet to induce hypercholesterolemia with simultaneous gavage of L. johnsonii CCFM1376 for 8 weeks. The biochemical parameters in the serum and liver of hypercholesterolemic mice were measured to assess the alleviating effect of L. johnsonii CCFM1376 on hypercholesterolemia. Bile acid content in the mouse liver, serum, distal ileum contents, and feces was determined using liquid chromatograph mass spectrometer (LC-MS). RNA was extracted from mouse ileum and liver, and the expression levels of relative genes implicated in bile acid metabolism were measured by quantitative real-time PCR (qPCR). Results: Compared to the model group, the group treated with L. johnsonii CCFM1376 exhibited significantly reduced levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), along with a significant increase in high density lipoproteins cholesterol (HDL-C) level. Moreover, hepatic levels of TC and LDL-C in the CCFM1376 group also decreased significantly. Furthermore, the content and amount of unconjugated bile acids in the hepatic-enteric circulation of the L. johnsonii CCFM1376 group significantly increased, and the total bile acid content in the feces also significantly increased. In the L. johnsonii CCFM1376 group, the relative expression levels of ileal farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were downregulated, while the relative expression level of CYP7A1 was upregulated. Conclusion: These results indicated L. johnsonii CCFM1376 improves hypercholesterolemia in mice by regulating the composition of bile acids. This provides a reference for probiotic strategy to regulate cholesterol metabolism.

Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder.

The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients. We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot. Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p<0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p<0.001), and 2.38 (1.48-3.83, p<0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795mmol/L with potential benefits to prevent relapse in NMOSD. In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.

Gender-specific effects of 3-month nutrition intervention on lipid profiles and insulin sensitivity

Dyslipidemia and insulin resistance are pivotal in diabetes mellitus and cardiovascular disease (CVD) pathogenesis, underscoring the necessity for lifestyle interventions(1). Previous research has highlighted the efficacy of dietary modifications in improving metabolic parameters and reducing CVD risk(2,3). However, understanding the gender-specific responses to such interventions remains underexplored. This study aims to investigate the gender-specific effects of a 3-month nutrition intervention, aimed at improving lipid profiles and insulin sensitivity in patients with dyslipidemia and insulin resistance.107 patients (pts), 53 men (49,5%), 54 women (50,5%), mean age 44,6 ± 11,3, mean BMI 33,1 ± 6,8, with dyslipidemia and insulin resistance were studied, 58 pts (54,2%) were with obesity. During the intervention, participants were provided with a dietary plan consisting of 3 meals, each of which contained vegetables (starchy and non-starchy), carbohydrates (whole grains, fruits, berries), proteins (poultry, fish, seafood, eggs, legumes, dairy products) and fats (olive oil, flax seeds, tree nuts). Pts were restricted on red and processed meat, butter, milk, trans fat, sugar, white flour products, and alcohol. The dietary intervention durated 12 weeks, during which pts maintained selfreported diet records to monitor their dietary intake. No pharmaceutical interventions were employed throughout this duration. Statistical analysis were based on using paired t-test with assessment of the dynamics of clinical indicators with 95% CI and calculation of the standardized effect size based on mean comparison.Among women after 12 weeks the mean reduction in serum low-density lipoprotein cholesterol (LDL-C) was −0.79 mmol/L (from 4.16 ± 0.85 to 3.37 ± 0.72) or -18.9%; triglycerides −0.33 mmol/L (from 1.51 ± 0.77 to 1.18 ± 0.45) or -21,85%; Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index decreased on -2,23 or -43,47% (from 5.13 ± 4.59 to 2.9 ± 2.56), insulin level dropped by 35,25% (from 17.87 ± 12.76 to 11.57 ± 7.89).Among men the reduction in values was the following: for LDL-C -0,85 mmol/L or -18,44% (from 4.16 ± 1.08 to 3.76 ± 0.88); for triglycerides -0,68 mmol/L or 33,66% (from 2.02 ± 1.07 to 1.34 ± 0.52); for HOMA-IR index -2,03 or -38,01% (from 5.34 ± 4.34 to 3.31 ± 2.74), for insulin -8,17 or -39,78% (from 20.54 ± 15.26 to 12.37 ± 8.66).The dynamics for these indicators are statistically significant (p &lt; 0.05).Dietary intervention led to significant reductions in serum LDL-C, triglycerides, HOMA-IR index, and insulin levels among both women and men, highlighting the effectiveness of dietary modification in improving lipid profiles and insulin sensitivity.

Serum megalin levels in type-2 diabetes mellitus with and without cardiovascular disease.

Low-density lipoprotein receptor-related protein-2 (LRP2), also called megalin, is a multi-ligand receptor of the LDL receptor gene family mediating reabsorption of ligands like Apo-A1. Type 2 diabetes mellitus (T2DM) may possibly disrupt megalin functions as it is found to be regulated by insulin. This might cause cardiovascular complications due to derangement in lipoprotein metabolism. The current study was carried out to assess the serum megalin levels among T2DM individuals with cardiovascular complications in the Indian population. This was a cross-sectional study involving 80 patients with T2DM. 40 T2DM patients with known cardiovascular disease were selected as cases and 40 of those without evidence of cardiovascular disease were selected as controls. Demographic details, DM duration and class of oral hypoglycemic agents (OHA) used were collected from medical records while details of lipid profile, fasting glucose, serum creatinine and urea were collected from laboratory information system. Serum megalin levels were estimated using left-over samples by ELISA. The study groups showed no statistical significance in baseline laboratory parameters except for serum creatinine and low density lipoprotein cholesterol (LDL-c). Mean serum megalin levels were statistically insignificant between cases and controls (0.91 ± 0.78 ng/mL vs. 0.85 ± 0.69 ng/mL, P 0.74).The subgroup analysis of serum megalin levels based on OHA consumption among cases was also statistically insignificant (P 0.056). Pearson's correlational analysis was statistically insignificant between serum megalin and lipid profile parameters among cases (P > 0.05). Serum megalin alone may not serve as a biomarker for cardiovascular disease.

CYP2C19 loss-of-function variants are independent risk factors for premature cerebral infarction: a hospital based retrospective study

ObjectiveCytochrome P450 2C19 (CYP2C19) plays an vital role in the course of cardiovascular and cerebrovascular diseases by affecting lipid metabolism. Triglyceride-glucose (TyG) is a comprehensive index composed of triglyceride and blood glucose, has relationship with some diseases. There was no research report on the association CYP2C19 polymorphisms, TyG with premature cerebral infarction (CI) (onset ≤ 65 years old) susceptibility.MethodsThis study retrospectively analyzed 1953 CI patients aged ≤ 65 years old from December 2018 to March 2024, and 1919 age-matched individuals with non-CI as controls. The relationship between CYP2C19 polymorphisms, TyG and premature CI risk were analyzed.ResultsThe proportion of hypertension, and diabetes mellitus in patients with premature CI was higher than those in controls. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and TyG levels in patients with premature CI were significantly higher than those in controls (all p < 0.05). The patients had lower CYP2C19 *1 allele frequency (63.3% vs. 69.6%, p < 0.001) and higher CYP2C19 *2 allele frequency (31.3% vs. 25.4%, p < 0.001) than controls. Logistic regression analysis showed that smoking history (odds ratio (OR): 1.193, 95% confidence interval (CI): 1.002–1.422, p = 0.048), hypertension (OR: 3.371, 95% CI: 2.914–3.898, p < 0.001), diabetes mellitus (OR: 1.911, 95% CI: 1.632–2.237, p < 0.001), CYP2C19 intermediate metabolizer (IM) + poor metabolizer (PM) phenotypes (OR: 1.424, 95% CI: 1.243–1.631, p < 0.001), and dyslipidemia (OR: 1.294, 95% CI: 1.077–1.554, p = 0.006) were independent risk factors for premature CI.ConclusionsHistory of smoking, hypertension, diabetes mellitus, dyslipidemia, and CYP2C19 IM + PM phenotypes were independently associated with premature CI susceptibility.

SHR-1918, a monoclonal antibody against angiopoietin-like 3, in healthy subjects: a randomized, double-blind, placebo-controlled, phase 1 study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) are important risk factors for atherosclerotic cardiovascular disease. Angiopoietin-like 3 (ANGPTL3) is involved in the regulation of lipid metabolism and can increase serum TG and LDL-C levels by reducing their clearance. SHR-1918 is an ANGPTL3 monoclonal antibody developed to inhibit ANGPTL3 activity, thereby reducing the level of TG and LDL-C. Purpose This phase 1 single ascending dose study aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1918 in healthy subjects. Methods Six dose cohorts were planned, including 100, 300, 450, 750, 900 (optional), and 1200 (optional) mg. For each cohort, 12 healthy subjects were enrolled and randomized (9:3) to receive single subcutaneous SHR-1918 or placebo. Subjects were observed for seven days post-dose and followed up to Day 148 for the 100 mg cohort and Day 190 for the other dose cohorts. The primary endpoints were safety and tolerability. Results A total of 72 subjects were enrolled in the six dose cohorts from 100 to 1200 mg (SHR-1918, n = 54; placebo, n = 18). SHR-1918 was well-tolerated at tested doses. Treatment-emergent adverse events (TEAEs) were reported in 49 (90.7%) subjects in the SHR-1918 group and 17 (94.4%) subjects in the placebo group. The most common TEAEs were upper respiratory tract infection (25.9% with SHR-1918 vs. 27.8% with placebo), protein urine present (22.2% vs. 22.2%), and blood uric acid increased (16.7% vs. 16.7%). All TEAEs were mild or moderate in severity. There were no serious adverse events or TEAEs leading to death. Serum concentration of SHR-1918 generally increased with increasing doses. Maximum serum concentration was reached 8.0 to 10.0 days after injection, and mean t½ was 29.4 to 53.3 days across the dose range. SHR-1918 exposure exhibited in a slightly greater-than-dose-proportional manner from 100 to 1200 mg. Serum LDL-C and TG levels markedly and rapidly decreased in all SHR-1918 dose cohorts and remained under the baseline value up to the end of follow-up period for the higher doses, whereas those in the placebo group were above baseline at most follow-up visits (Figure 1 and 2). In the 750 to 1200 mg cohorts, the largest decline in LDL-C from baseline ranged from -46.5% to -49.1%, and the maximum decrease in TG ranged from -67.4% to -82.8%. On Day 85, there remained to be 36.9% to 39.0% reduction in LDL-C and 59.9% to 79.1% reduction in TG for the higher doses. Anti-drug antibody was not detected in SHR-1918-treated subjects. Conclusions SHR-1918 was well-tolerated and showed promising efficacy in healthy subjects. A phase 2 study has initiated to evaluate SHR-1918 in hyperlipidemic patients (NCT06109831).Serum LDL-C after SHR-1918 injectionSerum TG after SHR-1918 injection