Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-ß/NF-κb signaling pathway: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. AIM OF THE STUDY: This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. MATERIALS AND METHODS: The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. RESULTS: We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-ß, and NF-κB proteins in the liver of hyperlipidemic rats. CONCLUSION: QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-ß/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.

Chylous aqueous humor caused by hyperlipidemia: A case report and literature review.

RATIONALE: Generally, there is no lipoprotein in aqueous humor, and chyle usually exists transiently in the body. Therefore, persistent chylous aqueous humor is rare. PATIENT CONCERNS: We report a case of a 39-year-old man with persistent milky white appearance over the right eye. DIAGNOSES: The patient had a history of poorly controlled diabetes for the past 2 years and central retinal vein occlusion of the same eye for the past 2 weeks. The patient's right eye had a uniform milky appearance in the anterior chamber, transparent cornea, and no keratic precipitate in the posterior cornea. Color Doppler ultrasound of the affected eye showed no obvious inflammation in the vitreous cavity. Laboratory tests revealed severe chylemia. The patient was finally diagnosed as chylous aqueous humor. INTERVENTIONS AND OUTCOMES: After conventional hypolipidemia and hypoglycemia treatment and locally glucocorticoid treatment. The milky white changes in the anterior chamber improved considerably and finally disappeared. LESSONS: Although the impact of hyperlipidemia on the cardiovascular system and digestive system is well known, its impact on the eyes is often overlooked. We report a rare case of unilateral chylous aqueous humor caused by hyperlipidemia. Through the analysis of this special case, we recommend that ophthalmologists should pay attention to the impact of blood lipid change on eyes.

Exploring barriers and facilitators of primary care physicians towards optimising statin therapy in patients with hyperlipidaemia in the very high-risk group: a qualitative study in Singapore.

OBJECTIVES: To explore the perspectives of primary care physicians with regard to the barriers and facilitators towards optimising statin therapy in patients with hyperlipidaemia in the very high-risk group. DESIGN: Qualitative descriptive study. SETTING: Four polyclinics in a public primary care institution in Singapore. PARTICIPANTS: Seven men and five women working as primary care physicians were recruited for in-depth interviews. RESULTS: The major barriers to statin optimisation identified were patients' lack of knowledge and awareness, patients' fear of side effects, negative external influences on patients, poor doctor-patient relationship, time constraint during consultations, physicians' unfamiliarity with guidelines, low health literacy among the local population and lack of strong national policy. The major facilitators identified were patient education, providing continuity of care, improving electronic medical record systems' capabilities, physician education and public education. CONCLUSION: We identified several important barriers and facilitators of statin therapy optimisation in this study. This information offers insights into the development of a multipronged approach to address barriers across different levels with the aim of optimising statin use, reducing cardiovascular events and improving patient outcomes.

[Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats].

OBJECTIVE: To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. METHODS: Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. RESULTS: Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). CONCLUSION: Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling.

Rice bran, a by-product of rice milling, is abundant in bioactive molecules and is highly recognized for its health-promoting properties, particularly in improving metabolic conditions. Building on this knowledge, we aimed to optimize the extraction conditions to maximize the functional efficacy of rice bran extract (RBE) and further validate its impact on lipid metabolism. We found that the optimized RBE (ORBE) significantly suppressed high-fat diet-induced weight gain, hyperlipidemia, and hepatosteatosis in mouse models. ORBE treatment not only suppressed lipid uptake in vivo, but also reduced lipid accumulation in HepG2 cells. Importantly, we discovered that ORBE administration resulted in activation of AMPK and inhibition of STAT3, which are both crucial players in lipid metabolism in the liver. Collectively, ORBE potentially offers promise as a dietary intervention strategy against hyperlipidemia and hepatosteatosis. This study underlines the value of optimized extraction conditions in enhancing the functional efficacy of rice bran.

ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.

While apolipoprotein E (apoE) expression by myeloid cells is recognized to control inflammation, whether such benefits can be communicated via extracellular vesicles is not known. Through the study of extracellular vesicles produced by macrophages derived from the bone marrow of Wildtype (WT-BMDM-EV) and ApoE deficient (EKO-BMDM-EV) mice, we uncovered a critical role for apoE expression in regulating their cell signaling properties. WT-BMDM-EV communicated anti-inflammatory properties to recipient myeloid cells by increasing cellular levels of apoE and miR-146a-5p, that reduced NF-κB signalling. They also downregulated cellular levels of miR-142a-3p, resulting in increased levels of its target carnitine palmitoyl transferase 1A (CPT1A) which improved fatty acid oxidation (FAO) and oxidative phosphorylation (OxPHOS) in recipient cells. Such favorable metabolic polarization enhanced cell-surface MerTK levels and the phagocytic uptake of apoptotic cells. In contrast, EKO-BMDM-EV exerted opposite effects by reducing cellular levels of apoE and miR-146a-5p, which increased NF-κB-driven GLUT1-mediated glucose uptake, aerobic glycolysis, and oxidative stress. Furthermore, EKO-BMDM-EV increased cellular miR-142a-3p levels, which reduced CPT1A levels and impaired FAO and OxPHOS in recipient myeloid cells. When cultured with naïve CD4+ T lymphocytes, EKO-BMDM-EV drove their activation and proliferation, and fostered their transition to a Th1 phenotype. While infusions of WT-BMDM-EV into hyperlipidemic mice resolved inflammation, infusions of EKO-BMDM-EV increased hematopoiesis and drove inflammatory responses in myeloid cells and T lymphocytes. ApoE-dependent immunometabolic signaling by macrophage extracellular vesicles was dependent on transcriptional axes controlled by miR-146a-5p and miR-142a-3p that could be reproduced by infusing miR-146a mimics & miR-142a antagonists into hyperlipidemic apoE-deficient mice. Together, our findings unveil a novel property for apoE expression in macrophages that modulates the immunometabolic regulatory properties of their secreted extracellular vesicles.

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

BACKGROUND: Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. METHODS: This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. RESULTS: In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia. CONCLUSION: The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

Nuclear FAK in endothelium: An intrinsic inhibitor of NF-κB activation in atherosclerosis.

BACKGROUND AND AIMS: Hyperlipidemia leads to the accumulation of oxidized low-density lipoprotein (oxLDL) within the vessel wall where it causes chronic inflammation in endothelial cells (ECs) and drives atherosclerotic lesions. Although focal adhesion kinase (FAK) is critical in proinflammatory NF-κB activation in ECs, it is unknown if hyperlipidemia alters FAK-mediated NF-κB activity in vivo to affect atherosclerosis progression. METHODS: We investigated changes in EC FAK and NF-κB activation using Apoe-/- mice fed a western diet (WD). Both pharmacological FAK inhibition and EC-specific FAK inhibited mouse models were utilized. FAK and NF-κB localization and activity were also analyzed in human atherosclerotic samples. RESULTS: ECs of hyperlipidemic mice clearly showed much higher levels of FAK activation in the cytoplasm, which was associated with increased NF-κB activation compared to normal diet (ND) group. On the contrary, FAK is mostly localized in the nucleus and inactive in ECs under healthy conditions with a low NF-κB activity. Both pharmacological and EC-specific genetic FAK inhibition in WD fed Apoe-/- mice exhibited a significant decrease in FAK activity and cytoplasmic localization, NF-κB activation, macrophage recruitment, and atherosclerotic lesions compared to the vehicle or FAK wild-type groups. Analyses of human atherosclerotic specimens revealed a positive correlation between increased active cytoplasmic FAK within ECs and NF-κB activation in the lesions. CONCLUSIONS: Hyperlipidemic conditions activate NF-κB pathway by increasing EC FAK activity and cytoplasmic localization in mice and human atherosclerotic samples. As FAK inhibition can efficiently reduce vascular inflammation and atherosclerotic lesions in mice by reversing EC FAK localization and NF-κB activation, these findings support a potential use for FAK inhibitors in treating atherosclerosis.

Acrochordons as a cutaneous sign of impaired carbohydrate metabolism, hyperlipidemia, liver enzyme abnormalities and hypertension: A case-control study.

BACKGROUND: Acrochordons are common and benign skin tumours. A few studies with contradictory results have been reported regarding the abnormalities of carbohydrate and/or lipid metabolisms in patients with acrochordons. OBJECTIVES: We aimed to determine if the presence of acrochordons could be a marker of diabetes, hyperlipidemia, liver enzyme abnormalities and hypertension by comparing with a control group. METHODS: A total of 110 patients having two or more acrochordons and age- and gender-matched 110 controls were included in the study. Localization, size and the total number of acrochordons were recorded in the patient group. Fasting plasma glucose (FPG), serum lipids and liver enzyme levels were tested in patient and controls. All participants underwent a standard 2-h oral glucose tolerance test with 75 g glucose. Diabetes mellitus and impaired glucose intolerance were diagnosed according to the American Diabetes Association criteria. Arterial blood pressures were measured in two groups. RESULTS: A total of 56 patients and 10 controls were diagnosed with overt DM. Thirteen per cent of the patients and 9% of controls had an impaired glucose tolerance test. The difference was statistically significant for the diagnosis of DM and not significant for the impaired glucose tolerance. The mean levels of FPG, total cholesterol, LDL cholesterol, triglyceride, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and alkaline phosphatase were significantly higher in patients than those in controls. Furthermore, serum levels of HDL were less in patients. Patients with acrochordons had higher systolic and diastolic blood pressures than controls. CONCLUSIONS: The results of our study suggest that acrochordons may represent a cutaneous sign for impaired carbohydrate or lipid metabolism, liver enzyme abnormalities and hypertension.

Determination of lipemia acceptance thresholds for 31 immunoassay analytes.

BACKGROUND: Lipemia is one of common endogenous interferences that can compromises sample quality and potentially influence results of various laboratory methods. Determination of the lipemic index or triglyceride concentrations are used to define the degree of lipemia. This study was aimed to establish lipemic index (LI) and triglyceride thresholds above where significant interference exists for 31 immunoassay analytes measured on Roche Cobas 6000. MATERIALS AND METHODS: The study was carried out following CLSI C56-A and EP07-ED3:2018 guidelines using sample pools spiked with increasing concentrations of lipid emulsion solution, reaching 70 mmol/L. To define the LI and triglyceride thresholds, the bias from concentration in the native sample was calculated at different lipemia degree and compared with allowable error limits based on biological variation or state-of-the-art technology. RESULTS: No lipemia interference was observed for 27 out of 31 analytes even at the highest concentrations of lipid emulsion (LI ranging from 1737 to 2086 mg/dL, triglyceride concentration 60.34-73.99 mmol/L). However, progesterone, 25-OH vitamin D, testosterone, and estradiol were negatively affected by lipemia at 217 mg/dL (9.58 mmol/L), 222 mg/dL (10.66 mmol/L), 478 mg/dL (18.81 mmol/L), and 941 mg/dL (35.82 mmol/L) of the LI (triglyceride concentration), respectively. CONCLUSION: Most immunoassays evaluated in this study were found to be robust to lipemia interference. By using these thresholds, laboratories can report the immunoassay results from analyzing a lipemic patient sample in many cases.

A cross-sectional study exploring the relationship between the dietary inflammatory index and hyperlipidemia based on the National Health and Nutrition Examination Survey (2005-2018).

BACKGROUND: Hyperlipidemia is closely associated with dietary patterns and inflammation. However, the relationship between hyperlipidemia and the inflammatory potential of diets remains unexplored. The research was conducted to examine the relationship between hyperlipidemia and dietary inflammatory index (DII). METHODS: The data utilized in the research were acquired from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. The information on dietary intake was gathered by conducting 24-h dietary recall interviews. Restricted cubic spline (RCS) and Survey-weighted logistic regression were utilized to determine the association between DII and hyperlipidemia. Furthermore, stratification analysis was carried out. RESULTS: This study included 8982 individuals with and 3458 without hyperlipidemia. Participants with hyperlipidemia exhibited higher DII scores than those without hyperlipidemia. Following adjustment for gender, age, race, education level, marital status, poverty, drinking status, diabetes, hypertension, smoking status, body mass index (BMI), chronic kidney disease (CKD), cardiovascular disease (CVD), and hemoglobin (Hb), the association between the prevalence of hyperlipidemia and DII remained significant. The RCS data demonstrated that the hyperlipidemia prevalence did not exhibit an increase until the DII score was approximately 2.78. Stratification analysis revealed that the association between DII and hyperlipidemia persisted in all subgroups. CONCLUSIONS: DII was associated with hyperlipidemia, and the threshold DII score for the risk of hyperlipidemia was 2.78.

Myofibroblasts: A New Factor Affecting the Hyperlipidemia-Induced Elastic Abnormality of Corpus Cavernosum in Rabbits Detected by 2-D Shear Wave Elastography.

OBJECTIVE: Two-dimensional shear wave elastography (2-D SWE) has been proven to detect hyperlipidemia-induced elastic abnormality in the corpus cavernosum. This study investigated cytological factors affecting the elasticity of the corpus cavernosum in rabbits with hyperlipidemia using single-cell RNA sequencing (scRNA-seq). METHODS: Male New Zealand white rabbits were randomly divided into a hyperlipidemia group (high-cholesterol diet) and a control group (standard diet). Penile 2-D SWE was performed to detect the elastic abnormality in the corpus cavernosum. ScRNA-seq was performed to observe cellular changes in the corpus cavernosum of rabbits with hyperlipidemia. Immunohistochemistry, immunofluorescence and histological examinations were conducted to verify the results of scRNA-seq. RESULTS: Two-dimensional SWE revealed that the Young's modulus of the corpus cavernosum was significantly greater in the hyperlipidemia group than that in the control group (p < 0.001). Histological findings revealed extracellular matrix accumulation within the corpus cavernosum, with stronger staining of collagen types I and Ⅲ. ScRNA-seq revealed that fibroblasts, smooth muscle cells, and endothelial cells were the major cell types in the corpus cavernosum. A novel subtype of fibroblasts (myofibroblast) was discovered in the hyperlipidemia group, which was verified by immunofluorescence staining and gene ontology analysis. Fibroblasts, smooth muscle cells and endothelial cells were three cellular sources for myofibroblasts. CONCLUSION: Myofibroblasts are activated and proliferate and secrete large amounts of collagen fibers in the corpus cavernosum during hyperlipidemia, leading to abnormal Young's modulus detected by 2-D SWE and their recognition as a new factor affecting the hyperlipidemia-induced elastic abnormality of the corpus cavernosum.

Acute effects of daily step count on postprandial metabolism and resting fat oxidation: a randomized controlled trial.

To examine the effects of daily step count on same-day fat oxidation and postprandial metabolic responses to an evening high-fat mixed meal (HFMM). Ten healthy participants (5 females, 30 ± 7 yr) completed four different daily step counts-2,000 (2 K), 5,000 (5 K), 10,000 (10 K), and 15,000 (15 K) steps-on separate days in randomized order. On experimental days, participants ate the same meals and walked all steps on an indoor track at a pace of 100 steps/min in three roughly equal bouts throughout the day. After the final walking bout, participants' resting energy expenditure (REE), respiratory exchange ratio (RER), and fat oxidation rate (FATOX) were measured. Blood samples were obtained before (BL) and 30-, 60-, 90-, 120-, and 240-min following consumption of an HFMM (960 kcal; 48% fat) to measure triglycerides (i.e., postprandial lipemia; PPL), nonesterified fatty acids (NEFAs), insulin, and glucose. Two-way ANOVAs indicated condition effects where PPL was significantly higher after 2 K versus 10 K (+23 ± 8 mg/dL, P = 0.027), and NEFAs were significantly higher after 15 K versus 2 K (+86 ± 23 µmol/L; P = 0.006). No differences were found for insulin, glucose, or REE among conditions (all P > 0.124). Similarly, RER (P = 0.054; ηp2 = 0.24) and FATOX (P = 0.071; ηp2 = 0.23) were not significantly different among conditions. In young adults, 10 K steps elicited the greatest decrease in PPL, an established cardiovascular disease risk factor. NEFA levels were highest after the 15 K condition, likely due to alterations in adipose tissue lipolysis or lipoprotein lipase activity with increased activity.NEW & NOTEWORTHY This randomized controlled trial demonstrated that walking 10,000, compared with 2,000, steps/day significantly reduced postprandial lipemia (PPL), an independent predictor of cardiovascular disease (CVD) following same-day evening meal consumption. These experimental data support walking 10,000 steps/day to lower CVD risk.

The association of serum Klotho concentrations with hyperlipidemia prevalence and lipid levels among US adults: a cross-sectional study.

BACKGROUND: Klotho has anti-oxidative and anti-inflammatory properties. However, little is known about whether high Klotho concentrations were associated with reduced hyperlipidemia risk and improved plasma lipid levels. METHODS: Participants with complete data on serum Klotho and plasma lipid concentrations from the 2007-2016 National Health and Nutrition Examination Survey were included. Weighted regression models were fitted to explore the association of Klotho concentrations with hyperlipidemia risk and plasma lipid levels while restricted cubic spline models were applied to explore the dose-response relationship. Additionally, we assessed the mediating effects of C-reaction protein (CRP) on the foregoing association. RESULTS: Individuals in the fourth and fifth quintile of serum Klotho had an adjusted odds ratio (OR) of 0.77 (95%CI: 0.65, 0.93) and 0.67 (95%CI: 0.65, 0.93) for hyperlipidemia. Doubling of serum Klotho concentrations was associated with decreased hyperlipidemia risk (OR = 0.81; 95%CI: 0.68, 0.95) and triglyceride levels (13.25 mg/dL; 95%CI: 4.02, 22.47), with a monotonic dose-response relationship. Individuals in the fourth and fifth quintile of serum Klotho had a 0.07 (95%CI: 0.002, 0.13), 0.08 (95%CI: 0.02, 0.15) and 0.05 (95%CI: -0.03, 0.12) mg/dL decreased CRP levels, with a marginally significant trend (Ptrend = 0.05). CONCLUSIONS: Higher Klotho concentrations were associated with reduced hyperlipidemia risk and triglyceride levels. Klotho supplementation maybe a promising method to intervene and prevent hyperlipidemia, but the underlying mechanism should be further explored.

Determination of chemical composition and investigation of potential of triphala powder in hypercholesterolemia in men in controlled randomized trial.

Hypercholesterolemia is a condition with elevated cholesterol and lipid profile. It is the leading reason behind myocardial infarction and coronary heart disease. It is observed in young people as well due to a sedentary lifestyle. Triphala powder has a hypolipidemic and anti-hypercholesterolemia effect. This study was designed to investigate the effect of triphala powder against hypercholesterolemia. This study also examined Triphala powder's chemical composition. Total phenolic and flavonoid content were examined. Encapsulated 400 mg and 600 mg Triphala powder were given to treatment groups I and II. Lipid profile parameters were measured and compared at 0 weeks and 10th weeks in all groups. All results were analyzed using ANOVA in IBM SPSS Statistics 20. Results of proximate analyses have shown that Okra pod powder contains moisture 12.27%, ash 11.25%, nitrogen-free extract 45.93%, crude protein 13.37%, crude fat 2.95% and crude fiber 14.23%. Mineral analysis showed that iron and manganese are major minerals in triphala powder. Triphala powder showed a significant reduction in lipid profile parameters in hypercholesterolemia. All results are taken significantly at p<0.05.

[Hypercholesterolemia and cardiovascular risk]. / Hypercholesterinämie und kardiovaskuläres Risiko.

Pharmacological reduction of LDL-cholesterol (LDL-C) is a major treatment strategy in limiting atherosclerotic cardiovascular (ASCVD) risk. Statins remain the primary therapeutic cornerstone in ASCVD prevention. Furthermore, ezetimibe, bempedoic acid, and PCSK9 inhibition have recently also shown to reduce cardiovascular risk. Unfortunately, a treatment gap remains between guideline-recommended LDL-C goals and what is achieved in real-world practice. An important reason for this is the limited use of novel and effective non-statin lipid-lowering therapies. In order to achieve LDL-C treatment goals and, ultimately, reduction of cardiovascular events, a combination lipid-lowering therapy needs to be considered as the standard of care for patients at very high cardiovascular risk.

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype-phenotype relationship for variants reported to date.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. METHODS: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. RESULTS: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6-7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype-phenotype correlation or SpliceAI-predicted data. CONCLUSIONS: This study reported two novel LPL variants and yielded new insights into the genotype-phenotype relationship as it pertains to LPL frameshift coding sequence variants.