low density lipoprotein
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2022 ◽  
Vol 11 ◽  
Tao He ◽  
Xu Li ◽  
Jiayuan Li ◽  
Zhu Wang ◽  
Yuan Fan ◽  

BackgroundThe aim of this study was to investigate the status of serum lipids during endocrine therapy.MethodsWe retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy.ResultsFor premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p<0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p<0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p<0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years.ConclusionsTAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.

2022 ◽  
Vol 10 (1) ◽  
Nikki L. Raftopulos ◽  
Tinashe C. Washaya ◽  
Andreas Niederprüm ◽  
Antonia Egert ◽  
Mariam F. Hakeem-Sanni ◽  

Abstract Background Prostate cancer growth is driven by androgen receptor signaling, and advanced disease is initially treatable by depleting circulating androgens. However, prostate cancer cells inevitably adapt, resulting in disease relapse with incurable castrate-resistant prostate cancer. Androgen deprivation therapy has many side effects, including hypercholesterolemia, and more aggressive and castrate-resistant prostate cancers typically feature cellular accumulation of cholesterol stored in the form of cholesteryl esters. As cholesterol is a key substrate for de novo steroidogenesis in prostate cells, this study hypothesized that castrate-resistant/advanced prostate cancer cell growth is influenced by the availability of extracellular, low-density lipoprotein (LDL)-derived, cholesterol, which is coupled to intracellular cholesteryl ester homeostasis. Methods C4-2B and PC3 prostate cancer cells were cultured in media supplemented with fetal calf serum (FCS), charcoal-stripped FCS (CS-FCS), lipoprotein-deficient FCS (LPDS), or charcoal-stripped LPDS (CS-LPDS) and analyzed by a variety of biochemical techniques. Cell viability and proliferation were measured by MTT assay and Incucyte, respectively. Results Reducing lipoprotein availability led to a reduction in cholesteryl ester levels and cell growth in C4-2B and PC3 cells, with concomitant reductions in PI3K/mTOR and p38MAPK signaling. This reduced growth in LPDS-containing media was fully recovered by supplementation of exogenous low-density lipoprotein (LDL), but LDL only partially rescued growth of cells cultured with CS-LPDS. This growth pattern was not associated with changes in androgen receptor signaling but rather increased p38MAPK and MEK1/ERK/MSK1 activation. The ability of LDL supplementation to rescue cell growth required cholesterol esterification as well as cholesteryl ester hydrolysis activity. Further, growth of cells cultured in low androgen levels (CS-FCS) was suppressed when cholesteryl ester hydrolysis was inhibited. Conclusions Overall, these studies demonstrate that androgen-independent prostate cancer cell growth can be influenced by extracellular lipid levels and LDL-cholesterol availability and that uptake of extracellular cholesterol, through endocytosis of LDL-derived cholesterol and subsequent delivery and storage in the lipid droplet as cholesteryl esters, is required to support prostate cancer cell growth. This provides new insights into the relationship between extracellular cholesterol, intracellular cholesterol metabolism, and prostate cancer cell growth and the potential mechanisms linking hypercholesterolemia and more aggressive prostate cancer.

Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 231
Ji Eun Kim ◽  
Ji Yeon Lee ◽  
Chang-Ho Kang

Hyperglycemia due to uncontrolled glucose regulation is widely known as cause of diabetes, non-alcoholic fatty liver disease (NAFLD), and other complications. NAFLD refers to a condition in which fat is excessively accumulated, whether inflamed or not, and has caused serious medical problems in recent years. The aim of this study was to explore the antihyperglycemia effects of Limosilactobacillus fermentum MG4295 (L. fermentum MG4295) in high-fat diet (HFD)-induced in vivo. We demonstrated the suitability of L. fermentum MG4295 as a probiotic by observing its stability, survivability, and proliferation under simulated gastrointestinal conditions, and safety, antibiotic susceptibility, hemolysis, and enzyme activity. The potential antihyperglycemic activity of L. fermentum MG4295 was investigated in an HFD and sugar-water-induced mouse model. Administration of this strain for 12 weeks showed an improved trend in glucose tolerance, insulin, alanine amino transferase, total cholesterol, low-density lipoprotein cholesterol, and glucagon-like peptide-1. Histopathological analysis revealed that L. fermentum MG4295 significantly reduced the histopathological scores of hepatic steatosis, inflammation, and hepatocellular hypertrophy in liver tissues and lipid content in adipose tissues. Administration of L. fermentum MG4295 upregulated IRS-1, AKT, and GLUT4 and downregulated G6Pc and PEPCK expression in liver and/or muscle tissues. Our results suggest that L. fermentum MG4295 can improve hyperglycemia. Furthermore, it can be used as a dietary functional supplement to manage blood glucose.

Victoria A. Metelskaya ◽  
Svetlana A. Shalnova ◽  
Elena B. Yarovaya ◽  
Vladimir A. Kutsenko ◽  
Sergey A. Boytsov ◽  

This study aimed to describe the dyslipidemia prevalence and pattern among adult populations from different regions (n = 13) of the Russian Federation (RF). Randomly selected samples (n = 22,258, aged 25–64) were studied according to the ESSE-RF protocol. Lipoprotein parameters were estimated by routine methods. Statistical analyses were performed using R software (v.3.5.1). The overall dyslipidemia prevalence was 76.1% (76.9/75.3% for men/women). In women, total cholesterol (TC) and low-density lipoprotein (LDL)-C levels gradually increased with age (from 4.72 to 5.93 and from 2.76 to 3.79 mmol/L, respectively); in men, they reached a maximum by 45–54 (5.55 and 3.55 mmol/L, respectively) and then decreased. No differences in high-density lipoprotein (HDL)-C in men of different ages were found, but slight decreases in HDL-C and apo AI were observed in women by 55–64 years. No pronounced associations between education and lipid levels in men were observed; higher-educated women showed significantly better lipoprotein profiles. Similar associations between lipids and income level were detected. Women from rural areas had higher TC and triglycerides than urban residents. Regardless of sex, rural residents had higher HDL-C and apo AI, and reduced apo B/apo AI. Conclusion: Information on the peculiarities of dyslipidemia prevalence and lipoprotein profile depending on sex, age, residential place, and socioeconomic status is useful for assessing the global ASCVD risk, and for risk modeling based on national data.

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 523
Xiang Li ◽  
Yan Xin ◽  
Yuqian Mo ◽  
Pavel Marozik ◽  
Taiping He ◽  

Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5–2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.

2022 ◽  
Jinchun He ◽  
Yaodong Wang ◽  
Yanpei Zhang ◽  
Zhijie He

Abstract (1) Background: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH. (2) Methods: In this retrospective, controlled not matched analysis, a total of 103 patients with FH and 106 non-FH controls were recruited into the study from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age. (3) Results: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp(a)) and non-HDL-C levels were significantly higher in patients with FH compared to the control (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses. (4) Conclusions: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention.

Weili Zheng ◽  
Michael Chilazi ◽  
Jihwan Park ◽  
Vasanth Sathiyakumar ◽  
Leslie J. Donato ◽  

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

2022 ◽  
Jin-Ming Zhang ◽  
Ming-Jie Chen ◽  
Jiong-Hui He ◽  
Ya-Ping Li ◽  
Zhi-Cai Li ◽  

Abstract LRP1, the low-density lipoprotein receptor 1, would be a novel candidate epilepsy gene according to our bioinformatic results and the animal study. In this study, we explored the role of LRP1 in Epilepsy and whether Beta-hydroxybutyrate, the principal ketone body of the ketogenic diet can treat epilepsy caused by LRP1 deficiency. UAS/GAL4 system was used to establish different genotype models. Flies were given Standard, High-sucrose, and ketone body food randomly. The bang-sensitive test was performed on flies and seizure-like behavior was assessed. Morphologic alteration of LRP1 defect in the brain was detected under GPF expression flies. We established global, astrocytic, and neuronal LRP1 knockdown flies. Whole body and glia LRP1 defect flies had a higher seizure rate compared to the control group in the behavior test. Ketone body decreased the seizure rate in behavior test in all LRP1 defect flies, compared to Standard and High sucrose diet. In morphologic experiments, we found that LRP1 deficiency caused partial loss of the ellipsoidal body and partial destruction of the fan-shaped body. Overexpression of glutamate transporter gene Eaat1 could mimic the ketone body effect on LRP1 deficiency flies. This study demonstrated that LRP1 defect globally or in astrocytes or neurons could induce epilepsy. The ketone body efficaciously rescued epilepsy caused by LRP1 knockdown. The results support screening for LRP1 mutations as discriminating conduct for individuals who require clinical attention and further clarify the mechanism of the ketogenic diet in Epilepsy, which could help Epilepsy patients making a precise treatment case by case.

2022 ◽  
Vol 8 ◽  
Younan Yao ◽  
Jin Liu ◽  
Bo Wang ◽  
Ziyou Zhou ◽  
Xiaozhao Lu ◽  

Background: The prognostic value of elevated lipoprotein(a) [Lp(a)] in coronary artery disease (CAD) patients is inconsistent in previous studies, and whether such value changes at different low-density-lipoprotein cholesterol (LDL-C) levels is unclear.Methods and Findings: CAD patients treated with statin therapy from January 2007 to December 2018 in the Guangdong Provincial People's Hospital (NCT04407936) were consecutively enrolled. Individuals were categorized according to the baseline LDL-C at cut-off of 70 and 100 mg/dL. The primary outcome was 5-year all-cause death. Multivariate Cox proportional models and penalized spline analyses were used to evaluate the association between Lp(a) and all-cause mortality. Among 30,908 patients, the mean age was 63.1 ± 10.7 years, and 76.7% were men. A total of 2,383 (7.7%) patients died at 5-year follow-up. Compared with Lp(a) &lt;50 mg/dL, Lp(a) ≥ 50 mg/dL predicted higher all-cause mortality (multivariable adjusted HR = 1.19, 95% CI 1.07–1.31) in the total cohort. However, when analyzed within each LDL-C category, there was no significant association between Lp(a) ≥ 50 mg/dL and higher all-cause mortality unless the baseline LDL-C was ≥ 100 mg/dL (HR = 1.19, 95% CI 1.04–1.36). The results from penalized spline analyses were robust.Conclusions: In statin-treated CAD patients, elevated Lp(a) was associated with increased risks of all-cause death, and such an association was modified by the baseline LDL-C levels. Patients with Lp(a) ≥ 50 mg/dL had higher long-term risks of all-cause death compared with those with Lp(a) &lt;50 mg/dL only when their baseline LDL-C was ≥ 100 mg/dL.

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