Decreased Serum High-density Lipoprotein Research Articles

A Cross Sectional Study of Lipid Profile In Ultrasonography-diagnosed Fatty Liver

ABSTRACT: Objective: The aim of this study is to conduct a descriptive cross sectional study to observe the relationship of lipid profile with fatty liver, as diagnosed by ultrasonography. Methodology: Study population consisted of 105 persons (50 females & 55 males) who were having non-alcoholic fatty liver disease, as diagnosed by ultrasonography. Serum lipid profile reports of the study population was tabulated and compared with grade I, II & III of ultrasonography-diagnosed fatty liver. Result: Grade I (mild) non-alcoholic fatty liver disease was seen in 84.7 %, grade II (moderate) in 13.3 % and grade III (severe) in 1.9% cases. Mean age of the study population was 48.3 years ranging from 25 years (minimum) to 79 years (maximum). Dyslipidemia was found in more than two thirds of our study population. Total cholesterol, triglyceride and low-density lipoprotein were increased in 67.6%, 65.7% and 67.6% respectively. High-density lipoprotein was decreased in 60.9% cases. Mean value of total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein were 233.5 gm/dl, 215.5 gm/dl, 148.7 gm/dl and 32.5 gm/dl respectively. When lipid profiles were compared with fatty liver, significant positive correlation was seen between non-alcoholic fatty liver disease with increased serum cholesterol, increased triglyceride, increased low-density lipoprotein & decreased serum high-density lipoprotein. P value was <0.001 in all the cases. Different grades of non-alcoholic fatty liver disease and individual lipid components showed no significant correlation. Conclusion: This study showed more than two thirds of ultrasonography-diagnosed non-alcoholic fatty liver had abnormal lipid profile. So, safe and non-invasive ultrasonography is very useful for screening and early detection of dyslipidemia in patients.

Influence of inflammation on lipid profile in chronic rheumatic diseases

Chronic inflammatory rheumatic diseases are associated with an increased risk of cardiovascular disease. In this group of patients, inflammation causes various changes in lipid metabolism, which in a chronic course may contribute to an increased risk of atherosclerosis. The most frequent abnormality is decreased serum high-density lipoprotein cholesterol (HDL–C) and increased triglyceride (TG) levels. This imbalance may be due to increased production and secretion of very low-density lipoprotein cholesterol (VLDL–С) in the liver and decreased clearance of TG-rich lipoproteins. The mechanisms by which inflammation lowers HDL–C levels are still unclear. Additionally, there is a persistent increase in lipoprotein (a) (Lp[a]) due to its increased synthesis. Thus, systemic inflammation negatively affects lipoprotein function: LDL–C oxidation becomes more active since there is the decreased ability of HDL–C to prevent this pathway. Moreover, chronic inflammation adversely affects the reverse cholesterol transport mechanism. The greater the severity of the underlying disease is associated with the more pronounced disorders in lipid metabolism. In general, approaches to the correction of lipid metabolism in patients with inflammatory rheumatic diseases are similar to those in patients from the general population.

Urine 3-Nitrotyrosine and Serum HDL as Potential Biomarkers of Depression

Depression (MDD) is a leading psychiatric entity worldwide, with a high impact on individual life and public health. In recent years, efforts have been made to elucidate its biological underpinnings. MDD biomarker research provides promise for a better understanding of the biochemical processes involved in its pathogenesis. Oxidative and nitrosative stress (O&NS) and lipid disturbances are reported as major factors favoring the occurrence of depression. A total of 29 patients with MDD and 30 healthy volunteers were examined using the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), and the Beck Depression Inventory (BDI). Blood and urine were collected to search for potential MDD biomarkers. O&NS parameters and β-amyloid were assessed in the urine, while cholesterol fractions were assessed in the blood. The group of depressed patients was characterized by higher concentrations of urine superoxide dismutase (SOD), 3-nitrotyrosine (3-NT), catalase (CAT), reduced glutathione (GSH), tryptophan (TRY), and serum triglycerides (TGA), along with lower levels of serum high-density lipoprotein (HDL). Elevated urine 3-NT and decreased serum HDL, considered together, were found to have the greatest potential as markers of depression. The study supports the importance of oxidative stress and cholesterol disturbances in MDD. Further research is required to assess their clinical usefulness as markers.

Significance of Decreased Serum High-density Lipoprotein Cholesterol Levels in Patients with Gastric Cancer

Significance of Decreased Serum High-density Lipoprotein Cholesterol Levels in Patients with Gastric Cancer

Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.

Demographic and Biochemical Parameters of Community Survey Participants with Metabolic Syndrome from Terai Region of Nepal

Introduction: The Metabolic Syndrome (MS) is a multifactorial disease associated with central obesity, hypertension, atherogenic dyslipidemia and impaired glucose tolerance. Low grade inflammatory and a prothrombotic state are also involved in MS. Aim: To explore the demographic and biochemical parameters of participants with MS in Terai region of Nepal using community based cross-sectional study. Materials and Methods: A cross-sectional study was carried out during September 2019-December 2019 in adult participants with central obesity (n=378) selected from three districts of Terai region of Nepal. International Diabetes Federation (IDF) criteria were used to define MS. The C-reactive protein-ultra sensitive, fibrinogen, and apolipoprotein-B were estimated as inflammatory, prothrombotic, and atherogenic dyslipidemia markers, respectively. Results: The MS was present in 283 participants with central obesity. The mean (±SD) age, height, weight, and BMI of the participants with MS were 46.36±12.52 years, 5.56±0.11 feet, 66.54±13.45 kg and 27.28±4.98 kg/m2, respectively. The mean (±SD) of biochemical factors were significantly different than their respective normal ranges: decreased serum High Density Lipoprotein (HDL) cholesterol in mg/dL (male: 34.50±9.93, p<0.001, female: 36.77±7.28, p<0.001), raised serum triglycerides level- 184.96±85.72 mg/dL (p<0.001), and impaired fasting serum glucose level 108.14±48.27 mg/dL (p=0.002). Significant increase in inflammatory (CRP-US: 1.12±2.17 mg/L, p<0.001), prothrombotic (fibrinogen: 3.42±1.04 gm/L, p<0.001) and atherogenic dyslipidemia marker (Apo-B: 149.35±59.13 mg/dL, p=0.003) from normal values were observed in subjects with MS. Conclusion: Lowered serum HDL cholesterol, increased triglycerides followed with impaired fasting glucose tolerance were observed as the major abnormal biochemical parameters and increased inflammatory and prothrombotic activities were present among participants with MS.

Orally administered octacosanol improves some features of high fructose-induced metabolic syndrome in rats.

We examined whether orally administered octacosanol, a long-chain aliphatic saturated alcohol, improves the features of high fructose-induced metabolic syndrome in rats. Five-week-old rats were fed a high fructose diet containing 60% fructose for 3 weeks. Then, the high fructose fed rats received a daily single oral administration of octacosanol (10 or 100 mg/kg body weight) with high fructose feeding for one week. Three- or four-week high fructose feeding increased insulin resistance, serum insulin, triglyceride, total cholesterol, free fatty acids, uric acid, and lipid peroxide concentrations, and hepatic triglyceride and cholesterol contents significantly and decreased serum high-density lipoprotein cholesterol and adiponectin concentrations significantly but did not affect blood pressure and hepatic lipid peroxide and reduced glutathione contents. Four-week high fructose feeding decreased hepatic ascorbic acid content significantly. Oral administration of octacosanol (10 or 50 mg/kg body weight) to high fructose-fed rats for the last 1-week fructose diet feeding attenuated these changes except serum insulin level and insulin resistance significantly and increased hepatic reduced glutathione content significantly. The higher dose of Oct decreased hepatic lipid peroxide content significantly. These results indicate that orally administered octacosanol improves dyslipidemia, hyperuricemia, hypoadiponectinemia, and oxidative stress associated with the features of high fructose-induced metabolic syndrome rats.

Efficacy of letrozole in treatment of male adolescents with idiopathic short stature

ObjectiveTo evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). MethodSeventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. ResultsHV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( P < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( t=2.78 and 2.20, all P < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( P>0.05), and both were higher than that in no intervention group (162±4 cm, P < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. ConclusionsLong term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.

Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation

Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population

IntroductionDyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.Material and methodsThis prospective cohort study comprised a population of 8698 men and women aged 35–65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.ResultsAfter 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19–2; P-value< 0.01; HR: 1.53; 95% CI: 1.18–1.98; P < 0.01; HR: 1.57; 95% CI: 1.27–2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12–6.57; P-value< 0.05).ConclusionIn the present study, TC baseline level was significantly associated with the risk of MI among men.

Echocardiographic findings in children with chronic kidney disease.

Cardiovascular diseases (CVD) are considered major cause of morbidity and mortality among children with chronic kidney disease (CKD). This study aims to determine the incidence of CVD in children with CKD, to analyze risk factors and early predictors for late onset atherosclerosis. Thirty-five CKD children [25 on regular hemodialysis (HD) and 10 on conservative management] were evaluated clinically. Left ventricular (LV) functions and carotid artery intima-media thickness (c-IMT) were assessed using conventional echocardiography, pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI). There was decreased E/A ratio and increased E/E' ratio in 66% and 77% of patients, respectively signifying diastolic cardiac dysfunction. There was a significant correlation between increased A' value (peak late diastolic annular velocity) and both increased serum cholesterol and anemia (P = 0.009, 0.004 respectively). Serum high density lipoprotein (HDL) significantly correlated negatively with inter-ventricular septal thickness and LV end-diastolic dimensions (P = 0.05, 0.02, respectively) and positively with E' value (peak early diastolic annular velocity) (P = 0.04). Abnormal c-IMT correlated significantly with HD duration (correlation coefficient = 0.428, P = 0.01) and with both increased serum cholesterol and decreased serum HDL (P = 0.021, 0.031, respectively). Diastolic dysfunction and abnormal LV dimensions are present in patients with CKD even those on conservative management. TDI appears to be more impressive than PWD in assessing early myocardial dysfunction. Increased c-IMT and dyslipidemia are prevalent in patients with CKD and more prevalent in patients on HD.

Associations Between the Apolipoprotein E ε4 Allele and Reduced Serum Levels of High Density Lipoprotein a Cognitively Normal Aging Han Chinese Population.

Background: Previous studies have confirmed that APOE genotype is associated with lipid metabolism, but related studies are inconsistent. Therefore, we conducted this cross-sectional study to explore the associations between apolipoprotein E (APOE) genotypes and serum levels of fasting blood sugar, triglycerides, total cholesterol, high density lipoprotein, and low density lipoprotein in a cognitively normal aging Han Chinese population.Methods: One hundred sixty-nine community elders with normal cognitive function were included in the study. Based on multiplex amplification refractory mutation system polymerase chain reaction (PCR), these subjects were divided into three groups: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of fasting blood sugar, triglycerides, total cholesterol, high density lipoprotein, and low density lipoprotein with APOE genotypes were assessed.Results: The results of Mann-Whitney analysis showed that the concentration of high density lipoprotein (HDL) in APOE E2 and E3 groups was higher than that in E4 groups (p < 0.05). Logistic regression analysis also suggested that a lower level of high density lipoprotein was associated with the E4 allele (adjusted odds ratio 0.164, 95% confidence interval 0.031~ 0.876, P = 0.034).Conclusion: APOE E4 is associated with decreased serum high density lipoprotein concentration in healthy elderly. However, the above conclusions need to be further verified.

Association between decreased HDL levels and cognitive deficits in patients with bipolar disorder: a pilot study

BackgroundCognitive deficits are common in patients with bipolar disorder (BD). Abnormal high density lipoprotein (HDL) levels have been implicated in cognitive deficits associated with ageing and neurodegenerative disorders. The present study aimed to investigate serum HDL levels, cognitive deficits and their association in patients with BD.MethodsThirty-seven patients with BD and 37 gender- and age-matched healthy controls (HCs) were recruited in a case–control study. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum HDL levels were measured using enzymatic colourimetry.ResultsThere was no difference in serum HDL levels between patients with BD and HCs after adjusting for gender, age, education and body mass index (BMI). Cognitive test scores in patients with BD were significantly lower than those in HCs except for the visuospatial/constructional index after adjusting for confounding variables. Serum HDL levels were positively correlated with RBANS total score and language score in patients with BD. Stepwise multiple regression analysis showed that serum HDL levels were significantly correlated with RBANS total score and subscale scores on immediate memory and language in patients with BD after adjusting for confounding factors.ConclusionsOur findings suggest that patients with BD had poorer cognitive performance than HCs except for the visuospatial/constructional domain, and decreased serum HDL levels were correlated with cognitive deficits, especially in immediate memory and language domains in patients with BD.

Current status of the reference system for measurement of serum high- and low-density lipoprotein cholesterol

Decreased serum high-density lipoprotein cholesterol (HDL-C) and increased low-density lipoprotein cholesterol (HDL-C) concentrations are important risk factors for cardiovascular diseases. Achieving accurate and comparable HDL-C and LDL-C results is the primary requirement for the prevention and treatment of cardiovascular diseases, in which reference system including reference method, reference materials and standardization programs are needed. The current reference method for HDL-C and LDL-C measurement is the β-quantification method developed by the United States Center for Disease Control and Prevention (CDC), a multi-step procedure involving ultracentrifugation, chemical precipitation, and cholesterol analysis by CDC reference method. This method uses a large amount of serum and is technically demanding which limited its application in standardization. The reduced volume β-quantification method uses a small volume of serum sample, is simple and high through put and is more applicable. However, both methods are sensitive to serum matrix. Commutability of reference materials should be evaluated when they are used to calibrate routine methods. Fresh (non-frozen) serum samples should be used for a split sample comparison between reference and direct methods. In addition, development of reference measurement procedure based on ultracentrifugation and preparation of commutable reference materials are the important work in lipoprotein standardization. Key words: Cholesterol,HDL; Cholesterol,LDL; Ultracentrifugation; Reference standards; Reproducibility of results

A systematic review of randomized controlled trials investigating the efficacy and safety of testosterone therapy for female sexual dysfunction in postmenopausal women.

The clinical sequelae of oestrogen deficiency during menopause are undoubted. However, the pathophysiological role of testosterone during the menopause is less clear. Several randomized, placebo-controlled clinical trials suggest that testosterone therapy improves sexual function in postmenopausal women. Some studies suggest that testosterone therapy has additional effects, which include increased bone mineral density and decreased serum high-density lipoprotein (HDL) cholesterol. Furthermore, the long-term safety profile of testosterone therapy in postmenopausal women is not clear. This article will provide a concise and critical summary of the literature, to guide clinicians treating postmenopausal women.

Aldose reductase C-106T polymorphism is associated with the risk of essential hypertension

Aldose Reductase (AR), encoded by AKR1B1, is a member of NADPH-dependent aldo-keto reductase superfamily. The C-106T polymorphism of AKR1B1 is closely related to the diabetic complications. Our previous studies have indicated that the expression of AR was increased in spontaneously hypertensive rats, suggesting the effect of AR in hypertension. Here we investigated whether AKR1B1 C-106T polymorphism was associated with essential hypertension (EH). AKR1B1 C-106T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the direct sequencing methods. 383 healthy subjects and 383 essential hypertensive patients were recruited in this study. The polymorphism of AKR1B1 C-106T in EH and normal tensive (NT) groups was in agreement with Hardy-Weinberg equilibrium. -106T allele of AKR1B1 C-106T variants was more frequent in EH patients compared with normal tensive subjects, indicating that -106T allele was a risk factor of EH (OR=1.841, 95%CI=1.366–2.481). In male patients, C-106T polymorphism was associated significantly with decreased serum high density lipoprotein cholesterol and higher systolic blood pressure levels. Our results suggest that -106T allele of AKR1B1 C-106T polymorphism may be associated with increased risk for EH in Chinese Han population.

Relationship between vascular function indexes, renal arteriolosclerosis, and renal clinical outcomes in chronic kidney disease.

Hypertension contributes critically to the development of renal arteriolosclerosis in chronic kidney disease (CKD), but the impact of vascular function indexes including central blood pressure on renal arteriolosclerosis has not been investigated. We determined whether vascular function indexes were related to renal arteriolosclerosis and renal clinical outcomes in CKD. This cross-sectional study was implemented in our hospital. Subjects were in-patients with CKD aged ≥20 years who underwent a renal biopsy. Vascular function indexes included central systolic blood pressure (SBP), cardio-ankle vascular index (CAVI), and renal resistive index. Central SBP was measured non-invasively using an automated device. Arteriolosclerosis was assessed histologically. Renal clinical outcomes included estimated glomerular filtration rate using serum creatinine (eGFRcreat) or cystatin C (eGFRcys), and the urinary albumin-creatinine ratio. Among vascular function indexes, central SBP was weakly correlated with renal arteriolosclerosis (n = 55). Renal arteriolosclerosis was increased in hypertensive or hyperuricaemic patients, and negatively correlated with serum high-density lipoprotein (HDL) cholesterol and eGFRcys, which were independent risk factors for renal arteriolosclerosis in a stepwise multivariate regression analysis. Of the vascular function indexes, CAVI showed the strongest correlation with all renal clinical outcomes. Central SBP was correlated with only urinary albumin-creatinine ratio, while renal resistive index was correlated with eGFRcreat and urinary albumin-creatinine ratio. Decreased serum HDL cholesterol was independently and most closely associated with renal arteriolosclerosis. Of the vascular function indexes, CAVI had the greatest impact on renal clinical outcomes, although it was not associated with renal arteriolosclerosis.

Decreased serum HDL at initial diagnosis correlates with worse outcomes for triple-negative breast cancer but not non-TNBCs.

This study aimed to evaluate the associations between metabolic syndrome (MS) and its components at initial diagnosis and outcomes of breast cancer including triple-negative breast cancer (TNBC) and non-TNBC. A cohort of 1,391 patients was reviewed between January 2004 and July 2008 (including 394 TNBC and 855 non-TNBC cases). MS and its components including body mass index (BMI), serum high-density lipoprotein (HDL) and triglycerides (TG) and their relationships with clinical outcomes were analyzed and then compared between groups. The incidences of MS and its components including BMI, the levels of HDL and TG were not differently distributed between the 2 groups (all p's >0.05). However, more TNBC than non-TNBC patients presented with hypertension and elevated serum glucose (20.3% vs. 14.9% and 16.0% vs. 10.8%, p = 0.018 and p = 0.012, respectively). TNBC patients had poorer 5-year relapse-free survival (RFS) than non-TNBC patients (72.8% vs. 84.2%, p<0.0001). Only in the TNBC group, patients with low high-density lipoprotein (HDL) demonstrated worse RFS and overall survival (OS; p<0.0001). Multivariate analysis identified that low HDL was an independent worse prognostic factor for both RFS (hazard ratio [HR] = 3.266, 95% confidence interval [95%CI], 2.087-5.112, p<0.0001) and OS (HR = 3.071, 95%CI, 1.732-5.445, p<0.0001) in TNBC patients. Decreased level of HDL may predict worse outcomes both in terms of RFS and OS for TNBC patients but not for non-TNBC patients. Further investigations are warranted to detect the underlying mechanisms.

1,3-Dichloro-2-propanol induced hyperlipidemia in C57BL/6J mice via AMPK signaling pathway

1,3-Dichloro-2-propanol (1,3-DCP) is a well-known contaminant that has been detected in a wide range of foods. Dietary intake represents the greatest source of exposure to 1,3-DCP. In the study, we first found 1,3-DCP could induce hyperlipidemia in C57BL/6J mice below 1mg/kg/day. We investigated serum lipid profile, liver total cholesterol (TC) and triglyceride (TG), histopathology of Liver and adipose tissue. The results showed 1,3-DCP dose dependently increased serum TG, TC and low-density lipoprotein cholesterol (LDL-C), decreased serum high-density lipoprotein cholesterol (HDL-C), increased relative liver weight, liver TG and TC, relative adipose tissue weight and enlarged the size of adipose cells. Because AMPK signal pathway is important in the process of lipid metabolism, we further investigated the effects of 1,3-DCP on AMPK signaling pathway in murine models. The results showed that 1,3-DCP (0.1–1mg/kg/day) decreased p-AMPK/tAMPK ratio, p-ACC/tACC ratio, PPARα expression, but increased FAT, SREBP1, HMGCR and FAS expression. These observations indicated that 1,3-DCP induced hyperlipidemia in C57BL/6J mice at least partially through regulating AMPK signaling pathway.

Dimethyl dimethoxy biphenyl dicarboxylate attenuates hepatic and metabolic alterations in high fructose-fed rats

High fructose consumption is currently linked to metabolic disorders including insulin resistance and dyslipidemia as well as hepatic steatosis. Dimethyl dimethoxy biphenyl dicarboxylate (DDB) is a hepatoprotectant with antioxidant and anti-inflammatory properties. The aim of this study therefore is to evaluate the effect of DDB on high fructose-induced metabolic disturbances and hepatic steatosis in a rat model. Male Wistar rats were allocated into three groups: control, fructose-fed (10% in drinking water and 10% in diet), and fructose-fed DDB (300 mg/kg, orally)-treated groups. Rats were fed a high-fructose diet for 6 weeks, while DDB was administered for an additional 2 weeks. High-fructose consumption elevated serum glucose and insulin levels and impaired oral glucose tolerance test, revealing insulin resistance. It also increased serum triglycerides and alanine aminotransferase as well as visceral fat content and decreased serum high-density lipoprotein. Additionally, histopathological examination revealed that high fructose intake induced hepatic steatosis. These alterations were associated with increased serum uric acid as well as hepatic content of malondialdehyde and nitric oxide (NO) in addition to overexpression of inducible NO synthase (iNOS). DDB administration significantly ameliorated the high fructose-induced hepatic and metabolic alterations. In conclusion, DDB ameliorates high fructose-induced metabolic disorders and hepatic steatosis in rats. Such protection is, at least in part, due to the inhibition of lipid peroxidation, decrease in iNOS overexpression, and reduction of elevated uric acid.