Lower Serum Lipid Research Articles

Low serum lipid levels as predictors of future suicide attempt in Parkinson's disease.

Low serum lipid levels as predictors of future suicide attempt in Parkinson's disease.

Tanyu Tongzhi Formula Delays Atherosclerotic Plaque Progression by Promoting Alternative Macrophage Activation via PPARγ and AKT/ERK Signal Pathway in ApoE Knock-Out Mice.

We previously demonstrated that the Tanyu Tongzhi Formula (TTF) significantly alleviated the clinical symptoms of patients with coronary heart disease and lowered serum lipid and inflammatory factor levels in patients with coronary heart disease and atherosclerosis model rats. However, the mechanism underlying TTF remains unknown. In this study, we examined the effect of TTF on atherosclerotic plaques in ApoE-/- mice and underlying mechanisms involved in macrophage polarization. Sixty male ApoE-/- mice were randomly divided into four groups. Mice in the control group were fed a regular diet, whereas experimental mice were fed a high-fat diet and received either saline (HFD group) or TTF at concentrations of 0.60 (TTF-L group) or 2.25 g/ml (TTF-H group) by daily oral gavage for 16 weeks. In the TTF-L and TTF-H groups, the levels of serum cholesterol, triglyceride, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were decreased, lipid content was significantly decreased, and percentage area of collagen/lipid increased in atherosclerotic plaque compared to in the HFD group. Moreover, we found TTF promoted the expression of alternative macrophage markers (Fizz1, Arg1, and Mrc) and suppressed the expression of M1 macrophage markers (TNF-α, IL-1β, and IL-6) by regulating peroxisome proliferator-activated receptor γ (PPARγ) expression and AKT/extracellular signal-regulated kinase (ERK) activation. We further investigated whether alternative macrophage was reduced when PPARγ was inhibited or the AKT/ERK signaling pathway was activated. TTF delayed atherosclerotic plaque progression by promoting alternative macrophage activation through increasing PPARγ expression and inhibiting AKT/ERK phosphorylation, providing a theoretical basis for its clinical application.

Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study

BackgroundThe cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs).MethodsGenetic variants strongly (p < 5 × 10–8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649).ResultsGenetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs.ConclusionsOur study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

Fructose-induced severe hypertriglyceridemia and diabetes mellitus: a cautionary tale.

SummaryDrinking fruit juice is an increasingly popular health trend, as it is widely perceived as a source of vitamins and nutrients. However, high fructose load in fruit beverages can have harmful metabolic effects. When consumed in high amounts, fructose is linked with hypertriglyceridemia, fatty liver and insulin resistance. We present an unusual case of a patient with severe asymptomatic hypertriglyceridemia (triglycerides of 9182 mg/dL) and newly diagnosed type 2 diabetes mellitus, who reported a daily intake of 15 L of fruit juice over several weeks before presentation. The patient was referred to our emergency department with blood glucose of 527 mg/dL and glycated hemoglobin (HbA1c) of 17.3%. Interestingly, features of diabetic ketoacidosis or hyperosmolar hyperglycemic state were absent. The patient was overweight with an otherwise unremarkable physical exam. Lipase levels, liver function tests and inflammatory markers were closely monitored and remained unremarkable. The initial therapeutic approach included i.v. volume resuscitation, insulin and heparin. Additionally, plasmapheresis was performed to prevent potentially fatal complications of hypertriglyceridemia. The patient was counseled on balanced nutrition and detrimental effects of fruit beverages. He was discharged home 6 days after admission. At a 2-week follow-up visit, his triglyceride level was 419 mg/dL, total cholesterol was 221 mg/dL and HbA1c was 12.7%. The present case highlights the role of fructose overconsumption as a contributory factor for severe hypertriglyceridemia in a patient with newly diagnosed diabetes. We discuss metabolic effects of uncontrolled fructose ingestion, as well as the interplay of primary and secondary factors, in the pathogenesis of hypertriglyceridemia accompanied by diabetes.Learning pointsExcessive dietary fructose intake can exacerbate hypertriglyceridemia in patients with underlying type 2 diabetes mellitus (T2DM) and absence of diabetic ketoacidosis or hyperosmolar hyperglycemic state.When consumed in large amounts, fructose is considered a highly lipogenic nutrient linked with postprandial hypertriglyceridemia and de novo hepatic lipogenesis (DNL).Severe lipemia (triglyceride plasma level > 9000 mg/dL) could be asymptomatic and not necessarily complicated by acute pancreatitis, although lipase levels should be closely monitored.Plasmapheresis is an effective adjunct treatment option for rapid lowering of high serum lipids, which is paramount to prevent acute complications of severe hypertriglyceridemia.

Distribution and prevalence of cardiovascular risk factors in a aging population of thalassemia patients: looking at the heart of the problem

Abstract Background β-thalassemia major is a hereditary genetic disease hindered by many comorbidities due to transfusion-related iron. Since the introduction of chelation therapy life expectancy of these patients has increased from the 16 years of 1964 to 50 years today, with a marked improvement in the quality of life. Iron-related heart disease is still a leading complication but diabetes mellitus and hypogonadism may impact the cardiovascular risk in these patients, with an expected change in heart involvement with this unprecedentedly seen aging of these patients. Target This study aims to evaluate the distribution and prevalence of cardiovascular risk factors in a population of thalassemia major patients, and their relationship with observed cardiovascular events and potential modifying factors. Methods and results One-hundred fifty-nine patients older than 18 years of age with clinical and molecular diagnosis of β-thalassemia major and at least 15 years of follow-up were included in this study. Mean age was 40.9±8.4 years. Low serum lipid levels with low HDL levels were noted, with 17.6% having diabetes mellitus and 62% with hypogonadism; Splenectomy was reported in 70%. During the observed period 3.8% of patients had at least one episode of heart failure, 35.9% showed early signs of heart failure, 22% received diagnosis of diastolic dysfunction, 38% had a left ventricular ejection fraction &amp;lt;55% and 21.4% showed supraventricular arrhythmias. Cardiovascular risk was then assessed using two algorithms (CUORE and Pooled Cohort Risk Equation - PCRE) and was generally low but despite that patients with hypogonadism (who showed lower cardiac T2* value than those without; p&amp;lt;0.001) showed a statistically significant correlation with the occurrence of cardiovascular events. Discussion The β-thalassemia population has a relatively low mean age, but shows a particular metabolic profile in association with numerous comorbidities: an increased prevalence of diabetes mellitus, low HDL values and frequent hypogonadism which tends to be associated with increased iron deposition in myocardium. The cardiovascular risk estimated by specific algorithms (CUORE and PCRE) was generally low, mainly due to the young age of the cohort, but the prevalence of cardiac events was not negligible. Conclusions The chronic accumulation of iron in the heart and the specific metabolic profile, particularly observed in patients with hypogonadism, allows us to define Major Thalassemia patients as a population at high cardiovascular risk from many points of view (iron-related myopathy, atherosclerosis and arrhythmias), which requires a specific follow-up program, to prevent and to identify early signs of these serious complications. Funding Acknowledgement Type of funding sources: None.

P51 - Topic: AS08-Treatment/AS08b-Current treatment options -Lenalidomide: LENALIDOMIDE TREATMENT IS ASSOCIATED WITH LOWER SERUM LIPIDS

P51 - Topic: AS08-Treatment/AS08b-Current treatment options -Lenalidomide: LENALIDOMIDE TREATMENT IS ASSOCIATED WITH LOWER SERUM LIPIDS

885P Molecular response to induction chemotherapy and its correlation with treatment outcome in head and neck cancer patients by means of NMR-based metabolomics

The aim of this prospective study is to identify the biomarkers associated with the effects of induction chemotherapy (iCHT) in terms of the favorable/weaker response to the treatment in locally advanced head and neck squamous cells carcinomas (LA-HNSCC) as well as to correlate the metabolic and clinical response to iCHT with the patients' overal survival. The studied group consisted of 53 LA-HNSCC patients treated with iCHT. The treatment tolerance was measured by the Common Terminology Criteria for Adverse Events (CTCAE). The response to the treatment was evaluated by the clinical, fiberoptic and radiological examinations made before and after iCHT (the TNM Classification of Malignant Tumors was used for classifying the extent of cancer spread). Proton nuclear magnetic resonance (1H NMR) serum spectra of the samples collected before and after iCHT were acquired with a 400 MHz spectrometer and analyzed using the multivariate and univariate statistical methods. Treatment failure occured in 24 patients with median follow-up (FU) 24.6 months (since the ent of post-iCHT radiotherapy). The median FU for the remaining 29 patients was 88 months. The molecular response to iCHT involves an increase of the serum lipids which is accompanied by the simultaneous decrease of alanine, glucose and N-acetyl-glycoprotein (NAG). Furthermore, in males, the iCHT induced changes in the lipid signals and NAG significantly correlate with the regression of the primary tumor. The regression of the primary tumor after iCHT showed no correlation with the treatment failure and FU. Male patients with treatment failure showed significantly lower serum lipids (both, pre- and post-iCHT) compared to those with favorable outcome. The NMR-based metabolomic study of the serum spectra revealed that iCHT induces the marked changes in the LA-HNSCC patients’ metabolic profiles and makes it possible to stratify the patients according to their response to iCHT as well as to possibly predict the treatment failure. These effects are sex dependent. Further studies on a larger scale accounting for sex and the clinical and metabolic factors are warranted.

Urinary metabolomics analysis of the protective effects of Daming capsule on hyperlipidemia rats using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Hyperlipidemia is recognized as one of the most important risk factors for morbidity and mortality due to cardiovascular diseases. Daming capsule, a Chinese patent medicine, has shown definitive efficacy in patients with hyperlipidemia. In this study, serum biochemistry and histopathology assessment were used to investigate the lipid-lowering effect of Daming capsule. Furthermore, urinary metabolomics based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was conducted to identify the urinary biomarkers associated with hyperlipidemia and discover the underlying mechanisms of the antihyperlipidemic action of Daming capsule. After 10weeks of treatment, Daming capsule significantly lowered serum lipid levels and ameliorated hepatic steatosis induced by a high-fat diet. A total of 33 potential biomarkers associated with hyperlipidemia were identified, among which 26 were robustly restored to normal levels after administration of Daming capsule. Pathway analysis revealed that the lipid-lowering effect of Daming capsule is related to the regulation of multiple metabolic pathways including vitamin B and amino acid metabolism, tricarboxylic acid cycle, and pentose phosphate pathway. Notably, the study demonstrates that metabolomics is a powerful tool to elucidate the multitarget mechanism of traditional Chinese medicines, thereby promoting their research and development.

Recombinant Human GLP-1 Beinaglutide Regulates Lipid Metabolism of Adipose Tissues in Diet-Induced Obese Mice

GLP-1 analogs are a novel class of injectable glucose-lowering agents with benefits of weight loss and improved cardiovascular outcomes. Adipose tissues are important regulators of lipid metabolism, but the role of GLP-1 in lipid metabolism of adipose tissues remains to be elucidated. The aim of this study was to determine the action of recombinant human GLP-1 (rhGLP-1) Beinaglutide (BN) in the insulin sensitivity and lipid metabolism of adipose tissues. We have shown that, after 6 weeks of BN treatment, high fat diet (HFD) induced obese mice displayed lower body weight, fat mass, and serum lipid levels. In addition, BN promoted the activity of insulin signaling in the white adipose tissues (WAT) in vivo and in vitro. Furthermore, by applying mass spectrometry-based lipidomic assay combined with RNA sequencing (RNA-seq), we have found that the BN treatment caused significant changes in content and composition of different lipid classes, including glycerolipids, glycerophospholipids and sphingolipids, as well as expression of genes in lipid metabolic pathways in the adipose tissues, particular in the subcutaneous WAT. Taken together, our data demonstrate that rhGLP-1 BN could resist HFD-induced obesity and lipid storage by targeting the composition of major lipid classes and the expression of genes in lipid metabolism of adipose tissues.

Pregnancy and lactation after Roux-en-Y gastric bypass worsen nonalcoholic fatty liver disease in obese rats and lead to differential programming of hepatic de novo lipogenesis in offspring.

Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.

Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study.

Simple SummaryCholesterol plays an important role in cell structure and cell proliferation. Altered lipid metabolism have been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development using large-scale, nationally representative data from the Korean National Health Insurance Service. During a median of 7.3 years follow-up, 26,891 incident HCCs were identified. The incidence of HCC gradually decreased according to the increase of total-cholesterol and LDL-cholesterol. This inverse association was consistent across subgroups stratified by the presence of liver cirrhosis or viral hepatitis. This large nationwide population-based study suggests that low lipid profile is an independent risk factor and preclinical marker for HCC.Background and Aims: Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development. Methods: Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009. Results: During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis. Conclusions: Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.

Anti-Diabetic and Hypolipidemic Effect of Coccinia Indica in Glucocorticoid Induced Insulin Resistance

This study explores the anti-diabetic, insulin sensitizing and hypolipidemic activity of Coccinia indica (C.indica) leaf extract (ethanolic) in glucocorticoid induced insulin resistance (IR). A 12 day study with 5 groups of 30 male Wistar albino rats, with 6 rats in each was conducted. The rats in all the groups except group 1 received dexamethasone (8mg/kg/i.p.) from 7th to 12th day to induce IR. The groups 1 and 2 received 2% gum acacia orally for 12 days whereas the groups 3 &amp; 4 received oral ethanolic extract of C.indica leaf in the dose of 1 and 2 gm/kg, respectively. The standard control (group 5) received metformin (1gm/kg) orally for 12 days. Fasting serum glucose, insulin and lipid levels were estimated at the beginning and end of the study. The insulin sensitivity indices (homeostatic model assessment of insulin resistance and sensitivity, fasting glucose to insulin ratio, hepatic &amp; atherogenic indices) were calculated. The body weight was monitored on alternate days. The liver weight, volume and histopathology were also done. Compared to group 2 rats, the group’s 3 &amp; 4 demonstrated significant(p&lt;0.05) dose dependent lowering of serum glucose, insulin and lipids as well as lowered IR, improved insulin sensitivity and reduced hepatic steatosis. Additionally, group 2 rats had low body weight and hepatomegaly. This extract demonstrated significant anti-diabetic, hypolipidemic and insulin sensitizing activity. Hence it can be used as an effective alternative for treating type2 diabetes mellitus.

The Role of BMI and Blood Pressure in the Relationship Between Total Cholesterol and Disability in Chinese Centenarians: A Cross-Sectional Study.

Background: Lower serum lipid metabolism might be associated with the decline of activity of daily living in the extreme longevity group. However, studies on models and possible paths of this correlation between total cholesterol (TC) and disability in centenarians are scarce. The aim of this study was to verify this correlation and explore the mediating effect of BMI and blood pressure on this relationship in Hainan centenarians.Methods: We conducted a cross-sectional analysis of 1002 centenarians from the China Hainan Centenarians Cohort Study (CHCCS). Data on demographics, anthropometry data, lifestyle, and TC levels were collected through interviews, physical examinations, and laboratory tests. The Barthel index and Lawton index, measuring the disability status, were used to estimate the activity of daily living (ADL) and instrumental activity of daily living (IADL). A multivariable logistic regression model was used to explore the correlation between disability and TC levels. Mediation analyses were used to explore the both direct and indirect effects of TC level on disability.Results: After adjusting for covariates, with 1 mmol/L increment in TC, the adjusted odds ratios (ORs) of ADL severe disability and ADL moderate & severe disability were 0.789(95%CI: 0.650–0.959) and 0.822(95%CI: 0. 0.699–0.966), respectively. There was a significant declining trend in the prevalence of different types of disability with increment in TC. The correlation was more pronounced among Hainan female centenarians. In the analysis of mediating effect among the female population, BMI significantly mediated the effect of TC levels on different types of disability. BMI and SBP, as chain mediators, multiply and chain mediated the effect of TC levels on IADL.Conclusion: Low TC levels might be correlated with a higher frequency of disability in female centenarians, and this correlation might be mediated by BMI and blood pressure.

Polysaccharides from fermented Momordica charantia L. with Lactobacillus plantarum NCU116 ameliorate metabolic disorders and gut microbiota change in obese rats.

Obesity is a chronic disease characterized by overweight resulting from fat accumulation, along with disturbance of metabolism and gut microbiota. Fermentation, as a green processing method, is beneficial for improving the nutrition capacity of food components. Polysaccharides are considered as one of the important components in food and are also potential supplements for anti-obesity treatment. This study aimed to investigate the anti-obesity effects of polysaccharides from fermented and non-fermented Momordica charantia L. with Lactobacillus plantarum NCU116 (FP and NFP) on obese rats by serum metabolomics and gut microbiota analysis. Metabolomics results revealed that abnormal lipid metabolism was formed due to obesity. The supplement of FP and NFP improved the glycerophospholipids, glycosphingolipids, and amino acid metabolism of the obese rats, which alleviated the hypercholesterolemia and overweight in rats. Furthermore, the disorder of gut microbiota was ameliorated by FP and NFP. FP promoted the growth of beneficial bacteria, such as phylum Firmicutes, Actinobacteria, and genera Anaerostipes, Coprococcus, Lactobacillus, and Bifidobacterium. FP also reduced several harmful bacteria belonging to the phylum Proteobacteria and genera Helicobacter. The positive correlation of the weight loss and lowering of serum lipids with the increased beneficial bacteria further elucidated that the anti-obesity effect of FP in obese rats is associated with the regulation of gut microbiota and serum metabolites. The results of this study could provide information for developing probiotic products in the future that may have beneficial effects on the prevention or treatment of obesity.

Protective effect of garlic juice on renal function and lipid profile in rats fed with high-fat diet

Background: Hyperlipidemia is one of the most challenging clinical disorders and is known to be a causative factor in a number of related conditions. Garlic has traditionally been used to lower serum lipids in hyperlipidemia patients. The present study evaluates the renoprotective role of garlic against induced changes in rat kidneys as a result of a high-fat diet (HFD). Materials and Methods: Twenty adult male Wistar rats were arranged into 4 groups: Group 1 (control) were fed a normal rat diet; Group 2 were fed an HFD (butter in a dose of 20g/100g food); Group 3 were fed fresh garlic juice (GJ) in their diet (6g/100g food); and Group 4 were fed with butter and GJ in their diet (HFD + GJ). The experimental period was 8 weeks. Serum lipid profiles and renal function tests were carried out and evaluated. Results: The HFD significantly increased body weight, total serum cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), uric acid, creatinine, and blood urea nitrogen (BUN), and decreased total protein and albumin, as compared to the control. In the HFD + GJ group, normal body weight was restored; serum levels of total cholesterol, creatinine, BUN, and albumin were similar to the control, and serum levels of triglyceride, LDL-C, uric acid, and total protein were partially restored to the levels of the control. Conclusions: The incorporation of GJ into an HFD resulted in improved lipid profile and kidney function. Hence, the consumption of GJ may be a useful supplement for renal protection in hyperlipidemic patients.

Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia

BackgroundReduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (“statins”) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease.MethodsA double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59 mmol/L (> 99.9 mg/dL). BUDCA was administered in two divided doses each day for 28 days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations.ResultsA total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000 mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (P = 0.0004) and LDL cholesterol by 10.4% (P = 0.0006), but no significant changes in triglyceride and HDL cholesterol concentrations.ConclusionsBUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid.Trial registrationThe study was registered on Clinicaltrials.gov (NCT03381287).

Effects of chitooligosaccharide supplementation on laying performance, egg quality, blood biochemistry, antioxidant capacity and immunity of laying hens during the late laying period

The effects of chitooligosaccharide (COS) supplementation in laying hen diets on egg production, egg quality, blood biochemistry, antioxidant capacity and immunity during the late laying period were investigated in this 10-week trial. A total of 3000 Fengda No.1 laying hens, 52 weeks of age, were randomly allocated to three treatment groups, each of which included five replicates of 200 hens. Treatments consisted of the basal diet only or the basal diet supplemented with COS at 75 or 125 mg/kg. Hens fed with both COS supplemented diets had improved hen-day egg production, egg mass and feed conversion ratio than control birds. The higher level of COS supplementation exerted positive effects on eggshell strength and eggshell thickness, but significantly decreased yolk colour. Addition of 125 mg/kg COS was also found to significantly increase serum albumin content and significantly decrease serum cholesterol level. Dietary supplementation with COS significantly decreased serum triglyceride level compared with birds fed the control diet. Moreover, COS significantly increased total antioxidative capacity and significantly decreased malondialdehyde level in serum, but had no significance on the activities of antioxidant enzymes. The only change in blood immune response compounds observed in this study was a significantly increased concentration of C3 when laying hens were fed COS supplemented diets. In conclusion, COS could improve laying performance and egg quality in hens during the late laying period. Inclusion of COS in the diet might be beneficial to hens’ health by lowering serum lipids, enhancing antioxidant activity and slightly enhancing immune ability. HIGHLIGHTS COS improved laying performance and egg quality in hens during the late laying period. Inclusion of COS in the diet might be beneficial to hens’ health by lowering serum lipids, enhancing the antioxidant activity and slightly enhancing immune ability. The optimum concentration of COS is 75 mg/kg in the basal diet in order to achieve an increased egg production, egg quality and health condition.

Intermittent Fasting Improves Lipid Metabolism Through Changes in Gut Microbiota in Diet-Induced Obese Mice.

BackgroundThe mechanism of how intermittent fasting (IF) improves metabolism is not fully understood. Our study aimed to explore the effect of IF on lipid metabolism in obese mice, specifically on the intestinal flora.Material/MethodsDiet-induced obese (DIO) mice were subjected to ad libitum (AL) feeding or IF (alternate-day fasting) for 30 days. We examined the lipid metabolism, fat distribution, gene expression of lipid metabolism, and intestinal flora in the mice.ResultsDespite having access to the same high-fat diet as the AL-fed groups, IF mice displayed pronounced weight loss, and their lipid metabolism significantly improved, mainly reflected in lower serum lipid levels and ameliorated liver steatosis. IF also reduced metabolic endotoxemia in DIO mice. The 16S ribosomal deoxyribonucleic acid gene amplicon sequencing suggested that IF did not change the community richness but had a tendency to increase community diversity in the intestinal flora. In addition, IF significantly reduced the ratio of Firmicutes to Bacteroidetes and increased the relative abundance of Allobaculum in the intestinal flora.ConclusionsIF can improve fat metabolism, reduce fat accumulation, promote white fat conversion to beige, and improve gut microbiota.

Disruption of the ERLIN-TM6SF2-APOB complex destabilizes APOB and contributes to non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by excess lipid accumulation in the liver without significant consumption of alcohol. The transmembrane 6 superfamily member 2 (TM6SF2) E167K missense variant strongly associates with NAFLD in humans. The E167K mutation destabilizes TM6SF2, resulting in hepatic lipid accumulation and low serum lipid levels. However, the molecular mechanism by which TM6SF2 regulates lipid metabolism remains unclear. By using tandem affinity purification in combination with mass spectrometry, we found that apolipoprotein B (APOB), ER lipid raft protein (ERLIN) 1 and 2 were TM6SF2-interacting proteins. ERLINs and TM6SF2 mutually bound and stabilized each other. TM6SF2 bound and stabilized APOB via two luminal loops. ERLINs did not interact with APOB directly but still increased APOB stability through stabilizing TM6SF2. This APOB stabilization was hampered by the E167K mutation that reduced the protein expression of TM6SF2. In mice, knockout of Tm6sf2 and knockdown of Tm6sf2 or Erlins decreased hepatic APOB protein level, causing lipid accumulation in the liver and lowering lipid levels in the serum. We conclude that defective APOB stabilization, as a result of ERLINs or TM6SF2 deficiency or E167K mutation, is a key factor contributing to NAFLD.

A study of lipid profile in maintenance hemodialysis patients

With increasing prevalence of Chronic Kidney Disease (CKD), CKD related cardiovascular diseases (CVD), end stage renal disease (ESRD) and the consequent financial burden of renal replacement therapy (RRT), the importance of CKD and its risk factors needs to be considered. Hence, lipid profile was studied in maintenance hemodialysis (MHD) subjects.An observational study consisting 100 patients diagnosed as ESRD on MHD of age group 18-70 years of both sex were selected from Nephrology unit, KIMS, Hubballi. Serum lipid profile was estimated by enzymatic method, urea by GLDH- Urease method, serum creatinine by Jaffe’s method.A significant patients had low serum lipid levels with mean ± standard deviation of Total cholesterol (mg/dl) 131.93±49.75, Triacylglyceride (mg/dl) 107.53±52.36, HDL-C (mg/dl) 28.93±10.06 &amp; LDL-C (mg/dl) 82.23±42.89 and serum creatinine (mg/dl) 8.28± 2.45 &amp; Blood urea (mg/dl) 110.51± 37.58ESRD patients are at higher risk and it is expected to have serum lipids as per NCEP-ATP-III guidelines. In contrast to this, where these levels are associated with increased risk of CVD, decrease values in dialysis patients are strongly correlated with increased morbidity including a higher risk of cardiovascular events and death. This observation is referred as “reverse epidemiology/risk factor–paradox”. It may be due to superimposed factors like inflammation and/or malnutrition that lead to lower cholesterol levels. In addition, chronic renal failure per se, primarily affects the metabolism of HDL-C and Triacylglyceride rich lipoproteins. Despite conflicting reports, hypercholesterolemia paradoxically appears to be associated with more favorable outcome in ESRD patients.