Plasma HDL Research Articles

Non-alcoholic Fatty Liver Disease in Asian Indian Adolescents and Young Adults

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the youth. The aim of the study was to conduct a metabolic risk factor profiling of NAFLD in adolescents and young adults in Chennai city in south India. Materials and Methods: The study participants included adolescents (n = 188) and young adults (n = 201). Ultrasonographic examination of the abdomen was done using a high-resolution B mode ultrasonography system. Based on the intensity of echogenicity, various grades of fatty liver were classified. Anthropometry, fasting plasma glucose, serum insulin, total cholesterol, triglycerides, and HDL and LDL cholesterol were estimated. χ2 analysis was performed to compare frequencies and t-tests on continuous or measurable data. Odds ratio (OR) was used as an indicator for strength of association. Results: From the total of 389 study participants, 70 had NAFLD which includes 48 with grade I, 21 with grade II, and one participant with grade III NAFLD. About 80% of the participants with NAFLD were adults (≥20 years) and more males were affected (70%) than females (30%). Generalized obesity was present in 90% of the participants with NAFLD. After adjusting for age and gender, obesity [OR: 5.88; 95% confidence interval (CI): 2.53–13.69; P-value: <0.001] and hyperglycemia [OR: 4.20; 95% CI: 1.75–10.08; P-value: <0.001] were significantly associated with NAFLD. Conclusion: With the higher prevalence rates of NAFLD noted in the study participants, prevention modalities should be adopted in the community by reducing obesity, healthy diet, and increased physical activity.

Effects of different ratios of crude protein and non-fibrous carbohydrates on growth, metabolism, physiology, nutrient utilization and muscle cellularity of Lophiosilurus alexandri, a carnivorous freshwater fish

The aim of this research was to evaluate the effects of different ratios of crude protein/non-fibrous carbohydrates (CP/NFC) on growth, metabolism, physiology, nutrient utilization efficiency and muscle cellularity of juvenile Lophiosilurus alexandri. Treatments consisted of isoenergetic diets (4500 kcal/kg) with CP/NFC ratios of 0.78; 1.02; 1.26 and 1.60, delivered for 75 days. Polynomial regression analysis showed that the different CP/NFC ratios affected weight gain and specific growth rate with estimated maximum values of 1.27 and 1.25, respectively. Feed conversion rate and the hepatosomatic index had minimum values with CP/NFC ratios of 1.33 and 1.02, respectively. Muscle and liver glycogen levels were maximized with CP/NFC content of 0.87 and 1.26, respectively. The CP/NFC ratio of 1.20 maximized the deposition of lipids in the muscle while that of 1.11 maximized the concentration of total soluble proteins in the same tissue. Plasma total cholesterol, non-HDL cholesterol and triglycerides increased linearly with increasing dietary CP/NFC ratio. Ratios estimated at 0.99, 0.94, 0.93 and 0.98 minimize the concentrations of HDL, total protein, alanine aminotransferase and creatinine in fish plasma, respectively. Nucleus diameter of hepatocytes increased linearly with increasing dietary CP/NFC ratio, while percentage of liver tissue nuclei decreased linearly. Hypertrophic muscle fibers were influenced by diets with the estimated ratio of 1.21 CP/NFC maximizing the occurrence of these fibers. Fish body crude protein increased linearly with increasing CP/NFC ratios in the diet. Fish body content of mineral matter, total phosphorus and visceral fat were minimized with the ratios of 1.34, 1.38 and 1.12, respectively. There were no effects of CP/NFC ratios on the viscerosomatic index, feed intake, carcass yield, the enzymes aspartate aminotransferase and gamma-glutamyl transferase, percentages of cytoplasmic and capillary sinusoids in liver tissue, and body dry matter, crude energy, total lipids, viscera dry matter. It is concluded that diets containing CP/NFC within 1.11–1.33 improve productive performance and nutrient use efficiency of fish. The different CP/NFC ratios also interfere with some plasma and metabolic variables that, associated with performance results, indicate a better physiological state of juvenile L. alexandri with an initial average weight of 30 g.

Oregano essential oil ( Origanum vulgare ) dietary supplementation improved growth performance, body protein retention and muscle hyperplasia of the Neotropical catfish Lophiosilurus alexandri

The use of essential oils (EO's) as feed additive has been explored as tool to improve fish growth and health. The aim of this study was to evaluate the oregano essential oil (OEO) (Origanum vulgare) dietary supplementation for the catfish Lophiosilurus alexandri. Four diets supplemented with different OEO levels (0.0, 1.0, 2.0 and 4.0 g kg−1) were evaluated in a feed trial conducted with fish of 15.7 ± 1.8 g and 9.5 ± 0.45 cm for 13 weeks. Were evaluated growth performance, biochemical parameters, intestinal histomorphometry, whole-body composition and muscle growth. Polynomial analysis showed that weight gain, length gain and specific growth rate were improved in fish fed with OEO supplemented diets, being 2.37, 2.56 and 2.33 g kg−1 the respective levels that maximize these variables. Plasma glucose, cholesterol, triglycerides, LDL and HDL increased with OEO levels between 1.80–2.47 g kg−1. Intestinal histomorphometry was not affected by OEO. Body protein content and hyperplasic muscle fibres were maximized with 2.10 and 2.25 g kg−1 OEO, respectively. Body moisture, total lipids, ash and hypertrophic muscle fibres were not affected by OEO. In conclusion, dietary supplementation with 2.10–2.56 g kg−1 OEO improves growth performance, body protein retention and muscle growth of L. alexandri.

Changes in plasma HDL and its subcomponents HDL2b and HDL3 regulate inflammatory response by modulating SOCS1 signaling to affect severity degree and prognosis of sepsis.

To explore if SOCS1 is regulated by plasma HDL and its subcomponents HDL2b and HDL3 to affect inflammatory reaction then to influence the severity degree and prognosis of sepsis. One hundred sepsis patients in ICU and 85 normal control persons from October 2018 to October 2019 in our hospital were enrolled. Adult male C57BL/6 mice were used to establish sepsis model by CLP method. HDL, CRP, and WBC count of human were measured using an auto-analyzer. Plasma HDL, IL-1β, and TNF-α proteins levels of mice were measured with ELISA. Microfluidic chip was used for plasma HDL2b and HDL3 detections. SOCS1 in liver and spleen of mice were measured by qRT-PCR. The relationship between plasma HDL//HDL2b and inflammatory indices/SOCS1 in liver/spleen was analyzed with spearman correlation coefficient method. The sepsis patients/mice were divided into non-survival and survival groups. The sepsis patients were divided into severe and mild sepsis patients based on the SOFA score or divided into high and low score groups according to the APACHE II score. The sepsis mice were divided into high and low score group based on the modified sepsis severity score criterion. Plasma HDL and HDL2b levels were significantly declined (P<0.01), while HDL3 was normal in both sepsis patients and mice (P>0.05). Plasma HDL and HDL2b were negatively associated with the serum CRP concentration and positively correlated with the prognosis and severity in sepsis patients (P<0.05). Moreover, the downregulated plasma HDL but not HDL2b was negatively related to increased SOCS1 mRNA levels in liver and spleen of mice, which were positively connected with TNF-α and IL-1β protein levels (P<0.05). Plasma HDL is downregulated in sepsis, which may facilitate inflammatory reaction then activate the SOCS1 signaling to regulate the severity and affect prognosis of sepsis. The decline of plasma HDL2b content could aggravate the severity and poor prognosis of sepsis through facilitating inflammatory reaction. The plasma HDL3 is not involved in sepsis. The more and further explorations may be needed.

Expression of Genes Encoding Nuclear Factors PPARγ, LXRβ, and RORα in Epicardial and Subcutaneous Adipose Tissues in Patients with Coronary Heart Disease.

The nuclear factors PPARγ, RORα, and LXRβ are involved in transcriptional control of adipogenesis and implicated in glucose and lipid metabolism. In adipose tissues, they regulate inflammation. This study focuses on expression of the PPARG, RORA, and LXRβ (NR1H2) genes in epicardial and subcutaneous adipose tissues in patients with coronary heart disease as well as with concomitant abdominal obesity. In patients with coronary heart disease and abdominal obesity, PPARG mRNA level in subcutaneous adipose tissue was reduced in comparison with control group. In patients with total coronary occlusions, LXRβ mRNA level in epicardial adipose tissue was reduced, and it positively correlated with plasma HDL cholesterol. Thus, in cases of concomitant abdominal obesity and chronic total coronary occlusions, coronary heart disease is characterized by down-regulated expression of the genes of various transcriptional adipogenesis-regulating factors in adipose tissue.

Dried mulberry fruit ameliorates cardiovascular and liver histopathological changes in high-fat diet-induced hyperlipidemic mice

Background and aimMetabolic disease encompasses most contemporary non-communicable diseases, especially cardiovascular and fatty liver disease. Mulberry fruits of Morus alba L. are a favoured food and a traditional medicine. While they are anti-atherosclerotic and reduce hyperlipidemic risk factors, studies need wider scope that include ameliorating cardiovascular and liver pathologies if they are to become clinically effective treatments. Therefore, the present study sought to show that freshly dried mulberry fruits (dMF) might counteract the metabolic/cardiovascular pathologies in mice made hyperlipidemic by high-fat diet (HF). Experimental procedureC57BL/6J mice were fed for 3 months with either: i) control diet, ii) HF, iii) HF+100 mg/kg dMF, or iv) HF+300 mg/kg dMF. Body weight gain, food intake, visceral fat accumulation, fasting blood glucose, plasma lipids, and aortic, heart, and liver histopathologies were evaluated. Adipocyte lipid accumulation, autophagy, and bile acid binding were also investigated. Results and conclusionHF increased food intake, body weight, visceral fat, plasma total cholesterol (TC) and low-density lipoprotein (LDL), TC/HDL ratio, blood glucose, aortic collagen, arterial and cardiac wall thickness, and liver lipid. Both dMF doses prevented hyperphagia, body weight gain, and visceral fat accumulation, lowered blood glucose, plasma TG and unfavourable TC/HDL and elevated plasma HDL beyond baseline. Arterial and cardiac wall hypertrophy, aortic collagen fibre accumulation and liver lipid deposition ameliorated in dMF-fed mice. Clinical trials on dMF are worthwhile but outcomes should be holistic commensurate with the constellation of disease risks. Here, dMF should supplement the switch to nutrient-rich from current energy-dense diets that are progressively crippling national health systems.

Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos.

Recent in vivo tracer studies demonstrated that targeted mass spectrometry (MS) on the Q Exactive Orbitrap could determine the metabolism of HDL proteins 100s-fold less abundant than apolipoprotein A1 (APOA1). In this study, we demonstrate that the Orbitrap Lumos can measure tracer in proteins whose abundances are 1000s-fold less than APOA1, specifically the lipid transfer proteins phospholipid transfer protein (PLTP), cholesterol ester transfer protein (CETP), and lecithin-cholesterol acyl transferase (LCAT). Relative to the Q Exactive, the Lumos improved tracer detection by reducing tracer enrichment compression, thereby providing consistent enrichment data across multiple HDL sizes from 6 participants. We determined by compartmental modeling that PLTP is secreted in medium and large HDL (alpha2, alpha1, and alpha0) and is transferred from medium to larger sizes during circulation from where it is catabolized. CETP is secreted mainly in alpha1 and alpha2 and remains in these sizes during circulation. LCAT is secreted mainly in medium and small HDL (alpha2, alpha3, prebeta). Unlike PLTP and CETP, LCAT’s appearance on HDL is markedly delayed, indicating that LCAT may reside for a time outside of systemic circulation before attaching to HDL in plasma. The determination of these lipid transfer proteins’ unique metabolic structures was possible due to advances in MS technologies.

Human apolipoprotein C1 transgenesis reduces atherogenesis in hypercholesterolemic rabbits

Background and aimsApolipoprotein (apo) C1 is a 6.6 kDa protein associated with HDL and VLDL. ApoC1 alters triglyceride clearance, and it also favors cholesterol accumulation in HDL, especially by inhibiting CETP in human plasma. Apart from studies in mice, which lack CETP, the impact of apoC1 on atherosclerosis in animal models expressing CETP, like in humans, is not known. This study aimed at determining the net effect of human apoC1 on atherosclerosis in rabbits, a species with naturally high CETP activity but with endogenous apoC1 without CETP inhibitory potential. MethodsRabbits expressing a human apoC1 transgene (HuApoC1Tg) were generated and displayed significant amounts of human apoC1 in plasma. ResultsAfter cholesterol feeding, atherosclerosis lesions were significantly less extensive (−22%, p < 0.05) and HDL displayed a reduced ability to serve as CETP substrates (−25%, p < 0.05) in HuApoC1Tg rabbits than in WT littermates. It was associated with rises in plasma HDL cholesterol level and PON-1 activity, and a decrease in the plasma level of the lipid oxidation markers 12(S)-HODE and 8(S)HETE. In chow-fed animals, the level of HDL-cholesterol was also significantly higher in HuApoC1Tg than in WT animals (0.83 ± 0.11 versus 0.73 ± 0.11 mmol/L, respectively, p < 0.05), and it was associated with significantly lower CETP activity (cholesteryl ester transfer rate, −10%, p < 0.05; specific CETP activity, −14%, p < 0.05). ConclusionsConstitutive expression of fully functional human apoC1 in transgenic rabbit attenuates atherosclerosis. It was found to relate, at least in part, to the inhibition of plasma CETP activity and to alterations in plasma HDL.

Discovery of Nonlipogenic ABCA1 Inducing Compounds with Potential in Alzheimer's Disease and Type 2 Diabetes.

Selective liver X receptor (LXR) agonists have been extensively pursued as therapeutics for Alzheimer's disease and related dementia (ADRD) and, for comorbidities such as type 2 diabetes (T2D) and cerebrovascular disease (CVD), disorders with underlying impaired insulin signaling, glucose metabolism, and cholesterol mobilization. The failure of the LXR-focused approach led us to pursue a novel strategy to discover nonlipogenic ATP-binding cassette transporter A1 (ABCA1) inducers (NLAIs): screening for ABCA1-luciferase activation in astrocytoma cells and counterscreening against lipogenic gene upregulation in hepatocarcinoma cells. Beneficial effects of LXRβ agonists mediated by ABCA1 include the following: control of cholesterol and phospholipid efflux to lipid-poor apolipoproteins forming beneficial peripheral HDL and HDL-like particles in the brain and attenuation of inflammation. While rare, ABCA1 variants reduce plasma HDL and correlate with an increased risk of ADRD and CVD. In secondary assays, NLAI hits enhanced cholesterol mobilization and positively impacted in vitro biomarkers associated with insulin signaling, inflammatory response, and biogenic properties. In vivo target engagement was demonstrated after oral administration of NLAIs in (i) mice fed a high-fat diet, a model for obesity-linked T2D, (ii) mice administered LPS, and (iii) mice with accelerated oxidative stress. The lack of adverse effects on lipogenesis and positive effects on multiple biomarkers associated with T2D and ADRD supports this novel phenotypic approach to NLAIs as a platform for T2D and ADRD drug discovery.

PREVALENCE OF DYSLIPIDEMIA IN CHRONIC KIDNEY DISEASE

BACKGROUND: Chronic kidney disease (CKD) is a worldwide health problem with increasing incidence and prevalence. The annual mortality rate of patients undergoing dialysis is more than 20%. The leading causes of morbidity and mortality in CKD are cardiovascular diseases, primarily atherosclerotic coronary artery disease. Dyslipidemia is a common complication of CKD. It is a signicant risk factor for the development of cardiovascular disease. Alteration in lipid prole correlates with declining glomerular ltration rate (GFR) and degree of proteinuria. AIM: Ÿ To identify the altered lipid prole in patients with chronic kidney disease. Ÿ To note the alterations in different lipoprotein fractions in chronic kidney disease patients. Ÿ To note the difference in lipid prole in CKD patients on conservative management and maintenance hemodialysis. MATERIALS AND METHODS: A Hospital-based observational Prospective study was conducted in the Department of Medicine, Santhiram medical college, and general hospital for six months. Chronic kidney disease patients who are non-diabetic were taken for the study with informed and written consent taken from the patient. RESULTS: Plasma triglycerides(153.14±54.37mg/dl) were elevated, and plasma HDL (36±43.5mg/dl) was decreased in CKD patients. There is no signicant elevation of total cholesterol levels. On comparing lipid proles of CKD patients on conservative management and hemodialysis, there was a signicant increase in triglycerides in the hemodialysis group. CONCLUSION: Signicant elevation of triglycerides and VLDL was observed in patients of CKD on hemodialysis. Further, a reduced HDL cholesterol level was also observed in both conservative and hemodialysis groups of CKD patients. Dyslipidemia observed in Uremic patients may contribute to accelerated atherosclerosis and further progression of chronic renal failure.

Clinical implications of intermittent Ramadan fasting on stable plaque psoriasis: a prospective observational study.

IntroductionPsoriasis is a chronic immune-mediated inflammatory disease. Environmental factors including diet have been supposed to play a role in its pathogenesis. Fasting in Ramadan consists of intermittent fasting in which participating Muslims refrain from eating and drinking from dawn up to sunset.AimTo validate the possible clinical consequences of Ramadan fasting for patients with psoriasis.Material and methodsThe study was conducted in Ramadan 2019. It included patients over 18 years who were diagnosed with stable chronic plaque psoriasis. PASI and BSA scores, body mass index and biochemical tests (including blood lipids, fasting blood glucose) were compared before and after a month of Ramadan fasting.ResultsThe study included 121 psoriasis patients. The mean PASI score was 4.36 ±3.22 at the beginning of the study, which was reduced to 3.51 ±1.26 at the end of the study. The difference was statistically significant (p = 0.001). There was no difference in the change of weight. We found a statistically significant difference in fasting plasma glucose, HDL and triglycerides. Only mild adverse events were noted during the study period.ConclusionsRamadan intermittent fasting has beneficial effects on severity of the disease in psoriasis patients with a reduction in PASI score and no serious health hazards. Thus, Ramadan intermittent fasting could be considered during treatment of psoriasis patients.

Borage oil intake by overweight young adults: no effect on metabolic rate; beneficial effects on plasma triglyceride and HDL cholesterol readings.

Some research has raised the possibility that gamma linolenic acid (GLA) can increase resting metabolic rate (RMR), which can help with weight control. However, in overweight young adults with a family history of obesity, no effect on RMR was seen after a 6 weeks treatment with borage oil (880 mg GLA per day) or evening primrose oil (540 mg GLA per day). On the other hand, borage oil did lower plasma triglyceride readings and raise HDL cholesterol readings (mean starting values in normal range for triglycerides, borderline low for HDL). No effect was seen for body mass index, plasma total cholesterol, LDL cholesterol, or glucose. Thus, in the type of subjects studied here, borage oil, a source of GLA, did not show promise as a weight control aid, but could help prevent undesirable readings for two blood lipid measures.

Review on impact of drinking on cardiovascular system and cardiovascular risk factors

The habitual mild intake of alcohol (510 g/day) and the incidence of coronary artery disease are known to be inversely related (CAD). This link includes many physiologically plausible mechanisms, including alcohol's amount of the drug effects on HDL cholesterol, plasma fibrinogen, and platelet aggregation. However, such a preventive impact against atheroma must be weighed against known negative regulation of blood pressure and triglycerides, as well as the potential negative consequences of episodic or binge drinking on a variety of other cardio -vascular final and risk factors. An alcoholic binge may worsen both silent myocardial ischaemia and angina in those who already have CAD. When people go through withdrawal after binge drinking, they experience a lot of symptoms. Blood operating pressure, together with increased platelet activation and changes in the balance of fibrinolytic factors, may explain the observed link between episodic excessive drinking and ischemic stroke. This has been observed in young men in particular, and it extends to an increase in both subarachnoid and intracerebral haemorrhage following binge drinking. Acute elevations in hypertension have been seen in males who drink mostly on weekends, compared to longer-term pressure effects in habitual daily drinkers, according to intervention studies in men. However, we have not been able to replicate the findings of unfavorable effects of binge drinking on the lipid profile that were reported in both animal and human research. Binge drinking may produce cerebrovascular spasms as well as ventricular and supraventricular arrhythmias, including atrial fibrillation. Alcohol-induced arrhythmia is thought to be the cause of alcohol-related sudden coronary mortality in those who already have CAD. As a result, future research into potential protective effects of alcohol against CAD must carefully examine the implications of drinking patterns for the connection. Co-timing of drinking with meals, cigarette smoking, and illegal drug use all have modifying effects that must be examined. Without this crucial knowledge, public health recommendations on alcohol and coronary artery disease would be restricted in breadth and possibly in effective.

Angiopoietin-like 3 inhibition of endothelial lipase is not modulated by angiopoietin-like 8

High plasma triglyceride (TG) levels and low HDL-C levels are risk factors for atherosclerosis and cardiovascular disease. Both plasma TG and HDL-C levels are regulated in part by the circulating inhibitor, angiopoietin-like 3 (ANGPTL3). ANGPTL3 inhibits the phospholipase, endothelial lipase (EL), which hydrolyzes the phospholipids of HDL, thus decreasing plasma HDL levels. ANGPTL3 also inhibits LPL, the lipase primarily responsible for the clearance of TGs from the circulation. Previous studies have shown that ANGPTL3 requires complex formation with the related ANGPTL protein, angiopoietin-like 8 (ANGPTL8), to efficiently inhibit LPL, but the role of ANGPTL8 in EL inhibition is not known. In this study, we characterized inhibition and binding of EL by ANGPTL3 and investigated the role of ANGPTL8 in EL inhibition. We found that inhibition of EL by ANGPTL3 was dose dependent and temperature dependent. Interestingly, this inhibition was diminished when EL was bound to endothelial cells or in the presence of heparin. Unlike previous findings with LPL, we found that ANGPTL8 did not significantly alter the binding or the inhibition of EL by ANGPTL3. In addition, we found that a common ANGPTL8 variant, which encodes an R59W mutation, altered the ability of ANGPTL3 to bind and inhibit LPL but not EL. Together, our data indicate that ANGPTL8 is not necessary for EL inhibition. We conclude that ANGPTL8 is specific for the regulation of TG-rich lipoproteins through the LPL pathway and that therapeutically targeting ANGPTL8 for the treatment of hypertriglyceridemia or cardiovascular disease may have different outcomes than targeting ANGPTL3.

Regional Variation in Genetic Control of Atherosclerosis in Hyperlipidemic Mice

Atherosclerosis is a polygenic disorder that often affects multiple arteries. Carotid arteries are common sites for evaluating subclinical atherosclerosis, and aortic root is the standard site for quantifying atherosclerosis in mice. We compared genetic control of atherosclerosis between the two sites in the same cohort derived from two phenotypically divergent Apoe-null (Apoe−/−) mouse strains. Female F2 mice were generated from C57BL/6 (B6) and C3H/He (C3H) Apoe−/− mice and fed 12 weeks of Western diet. Atherosclerotic lesions in carotid bifurcation and aortic root and plasma levels of fasting lipids and glucose were measured. 153 genetic markers across the genome were typed. All F2 mice developed aortic atherosclerosis, while 1/5 formed no or little carotid lesions. Genome-wide scans revealed 3 significant loci on chromosome (Chr) 1, Chr15, 6 suggestive loci for aortic atherosclerosis, 2 significant loci on Chr6, Chr12, and 6 suggestive loci for carotid atherosclerosis. Only 2 loci for aortic lesions showed colocalization with loci for carotid lesions. Carotid lesion sizes were moderately correlated with aortic lesion sizes (r = 0.303; P = 4.6E-6), but they showed slight or no association with plasma HDL, non-HDL cholesterol, triglyceride, or glucose levels among F2 mice. Bioinformatics analyses prioritized Cryge as a likely causal gene for Ath30, Cdh6 and Dnah5 as causal genes for Ath22. Our data demonstrate vascular site-specific effects of genetic factors on atherosclerosis in the same animals and highlight the need to extend studies of atherosclerosis to sites beyond aortas of mice.

Factors affecting egg consumption in young consumers

Factors affecting egg consumption in young consumers

Abstract 15859: Fibroblast Growth Factor 23 and Myocardial Infarction in the Boston Puerto Rican Health Study

Background: FGF-23 is an endocrine regulator of phosphate metabolism as well as also a potent biomarker that mediates cardiovascular remodeling, with markedly elevated plasma concentration associated with the occurrence of morbid cardiovascular events such as myocardial infarction. This association usually indicates risk of developing further adverse cardiovascular events in individuals that are already susceptible to repeat morbid cardiovascular outcomes. This cross-sectional epidemiological study aims at investigating the risk association between FGF-23 and individuals in the 8 th year cohort of the Boston Puerto Rican Health Study (BPRHS) that have self-reported clinical cardiovascular disease in the form of myocardial infarction. Methods: FGF-23 plasma concentration was measured by ELISA in 496 participants of the fourth wave of the Boston Puerto Rican Health Study (BPRHS). Multivariate logistic regressions were used to analyze the cross-sectional association of plasma FGF-23 quartile distribution with self-reported clinical diagnosis of myocardial infarction (MI). Results: The crude model for the association between FGF-23 and MI showed increased risk across the 2 nd , 3 rd and 4 th quartiles, OR (95% CI); 1.27 (0.48-3.34), 1.13 (0.42-3.04), and 3.13 (1.33-7.33), respectively. The relationship with the highest vs lowest quartile remained significant after adjusting for age, sex and BMI, OR (95% CI); 2.91 (1.15-7.36). With further adjustment for diabetes, smoking, plasma total cholesterol, HDL cholesterol and triglycerides, results were attenuated, and the latter comparison was no longer statistically significant, OR (95% CI); 2.15 (0.79-5.79). The test for trend across the quartiles yielded a p value of 0.03. Conclusion: Within this population of older Puerto Rican adults, FGF-23 was not significantly associated with increased likelihood of self-reported history of myocardial infarction. Longitudinal studies, using clinical parameters that objectively measure the progression of cardiovascular disease are needed to assess the prognostic value of FGF-23 for future cardiovascular outcomes.

Chronic Disruption of the Late Cholesterol Synthesis Leads to Female-Prevalent Liver Cancer.

Simple SummaryHepatocellular carcinoma is a disease with a variety of molecular triggers and is usually reported to prevail in males. However, after the menopause, the disease is also increasing in the female population. Herein, we discovered that chronic depletion of cholesterol synthesis due to the knock-out of the gene Cyp51 from this pathway leads to female prevalent hepatocarcinogenesis in aging mice. There is a high similarity between our mouse model and the situation in humans. Multiple deregulated pathways of hepatocarcinogenesis are shared. A female-dependent metabolic reprogramming leading to this type of liver cancer is exposed for the first time and reflects on deregulated cholesterol synthesis as the metabolic trigger. These data are of crucial importance. Despite the higher overall prevalence of hepatocellular carcinoma in males, we need tools and biomarkers to further stratify patients and offer better diagnosis and treatment options to both sexes.While the role of cholesterol in liver carcinogenesis remains controversial, hepatocellular carcinoma generally prevails in males. Herein, we uncover pathways of female-prevalent progression to hepatocellular carcinoma due to chronic repression of cholesterogenic lanosterol 14α-demethylase (CYP51) in hepatocytes. Tumors develop in knock-out mice after year one, with 2:1 prevalence in females. Metabolic and transcription factor networks were deduced from the liver transcriptome data, combined by sterol metabolite and blood parameter analyses, and interpreted with relevance to humans. Female knock-outs show increased plasma cholesterol and HDL, dampened lipid-related transcription factors FXR, LXRα:RXRα, and importantly, crosstalk between reduced LXRα and activated TGF-β signalling, indicating a higher susceptibility to HCC in aging females. PI3K/Akt signalling and ECM-receptor interaction are common pathways that are disturbed by sex-specific altered genes. Additionally, transcription factors (SOX9)2 and PPARα were recognized as important for female hepatocarcinogenesis, while overexpressed Cd36, a target of nuclear receptor RORC, is a new male-related regulator of ECM-receptor signalling in hepatocarcinogenesis. In conclusion, we uncover the sex-dependent metabolic reprogramming of cholesterol-related pathways that predispose for hepatocarcinogenesis in aging females. This is important in light of increased incidence of liver cancers in post-menopausal women.

Blood plasma levels of biomarkers of liver status and lipid profile among nail technicians occupationally exposed to low-level mixture of volatile organic compounds

PurposeNail technicians (NTs) are exposed to a low-level mixture of volatile organic solvents (VOCs), yet the health hazards related to such exposure are unknown. This study thus aimed to compare the blood plasma levels of selected biomarkers related to liver status and lipid profile among occupationally exposed NTs and unexposed controls. Associations between out-of-normal-range levels of such biomarkers and occupational exposure to VOCs mixture have also been investigated.MethodsThe study enrolled 145 female NTs and 152 unexposed controls. Biochemical analyses were performed using spectrophotometric assays and obtained data were analyzed using general linear model and Poisson regression modelling adjusted to multiple confounders.ResultsCompared to controls, NTs presented significantly increased plasma activities of ALT (2.04 ± 0.63 ln-U/l vs. 1.25 ± 0.71 ln-U/l; p < 0.0001) and AST (2.73 ± 0.25 ln-U/l vs. 2.08 ± 0.95 ln-U/l; p < 0.0001), and significantly increased plasma levels of TG (4.38 ± 0.53 ln-mg/dl vs. 4.21 ± 0.42 ln-mg/dl; p < 0.05) and TC/HDL ratio (1.18 ± 0.36 vs. 1.02 ± 0.27; p < 0.0005). Plasma levels of HDL were significantly lower among NTs (4.02 ± 0.29 ln-mg/dl vs. 4.21 ± 0.26 ln-mg/dl; p < 0.0001). Moreover, NTs were found to present significantly increased risk of occurrence of clinically relevant plasma HDL levels below 3.91 ln-mg/dl (i.e., 50 mg/dl; RR = 1.58, 95% CI 1.07–2.32, p < 0.05), as well as increased risk of clinically relevant TC/HDL ratio above the normal range limit of 3.5 (RR = 1.68, 95% CI 1.19–2.35, p < 0.005), as compared to unexposed controls.ConclusionNail technicians are subject to adverse changes in selected plasma biomarkers related to liver functions, some of which may be of clinical relevance.

Association study of genetic variants at TTC32-WDR35 gene cluster with coronary artery disease in Chinese Han population.

BackgroundTTC32‐WDR35 gene cluster has been genome‐wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.MethodsWe performed a case‐control study enrolling 935 CAD cases and 935 age‐sex‐frequency‐matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.ResultsThis study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54‐0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42‐0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.ConclusionsSNP rs721932 at TTC32‐WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.