Serum Lipid Concentrations Research Articles

Cheong-sang-bang-pung-san alleviated hepatic lipid accumulation by regulating lipid metabolism in vitro and in vivo.

Introduction: The occurrence of fatty liver disease, resulting from the accumulation of excessive fat within the liver, has been showing a significant and rapid increase. This study aimed to evaluate the therapeutic effects of Cheong-sang-bang-pung-san extract (CB) on fatty liver disease, and to elucidate the underlying mechanisms. Methods: We used a high-fat diet (HFD)-fed fatty liver mice and free fatty acid (FFA) induced HepG2 cell lipid accumulation model. The levels of serum, hepatic, and intracellular lipid content were assessed. Histopathological staining was used to evaluate the extent of hepatic lipid accumulation. Real-time polymerase chain reaction and Western blotting were conducted to examine the expression of factors associated with lipid metabolism. Results: We demonstrated that treatment with CB dramatically reduced body weight, liver weight, and fat mass, and improved the serum and hepatic lipid profiles in HFD-induced fatty liver mice. Additionally, CB alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including fatty acid uptake, triglyceride and cholesterol synthesis, and fatty acid oxidation, at the mRNA as well as protein levels. In free fatty acid-treated HepG2 cells, CB significantly reduced intracellular lipid accumulation by regulating lipid metabolism via the activation of AMP-activated protein kinase. Conclusion: These findings provide insights into the mechanisms underlying CB's effects on liver steatosis and position of CB as a potential therapeutic candidate for managing lipid metabolic disorders.

The Effect of Hyperlipidemia as a Risk Factor on Postoperative Complications in Patients Undergoing Anterior Cervical Discectomy and Fusion.

Retrospective cohort study. To analyze the effect of hyperlipidemia (HLD) on postoperative complications in patients who underwent anterior cervical discectomy and fusion (ACDF). ACDF represents the standard procedure performed for focal anterior nerve root or spinal cord compression with low complication rates. HLD is well known as a risk factor for major complications after vascular and transplant surgery, and orthopedic surgery. To date, there have been no studies on HLD as a risk factor for cervical spine surgery. Patients who underwent ACDF from 2010 through quarter 3 of 2020 were enrolled using the MSpine subset of the PearlDiver Patient Record Database. The patients were divided into single-level ACDF and multilevel ACDF groups. In addition, each group was divided into subgroups according to the presence or absence of HLD. The incidence of surgical and medical complications was queried using relevant International Classification of Disease and Current Procedural Terminology codes. Charlson Comorbidity Index was used as a broad measure of comorbidity. χ 2 analysis, with populations matched for age, sex, and Charlson Comorbidity Index, was performed. A total of 24,936 patients who underwent single-level ACDF and 26,921 patients who underwent multilevel ACDF were included. In the multilevel ACDF group, wound complications were significantly higher in the patients with HLD. Among medical complications, myocardial infarction, renal failure, and urinary tract infection/urinary incontinence were significantly higher in the patients with HLD in both groups. Revision surgery and readmission were significantly higher in the patients with HLD who underwent multilevel ACDF. In patients who underwent ACDF, several surgical and medical complications were found to be higher in patients with HLD than in patients without HLD. Preoperative serum lipid concentration levels and management of HLD should be considered during preoperative planning to prevent postoperative complications in patients undergoing ACDF.

Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.

We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.

The necessity for improving lipid testing reagents: A real world study

BackgroundWe investigated the interference of vitamin C (VitC), glycerol fructose, lipoprotein X (LpX) and lipemia on the analysis of serum lipids. MethodsSerum were collected from 44 patients with VitC infusion, serum lipid concentrations before and after VitC auto-oxidation were compared. Serum of 31 patients with glycerol fructose infusion were collected, triglycerides (TG) measured by glycerol blanking and non-blanking reagents were compared. Forty-four serum samples suspected to contain LpX were collected, LDL-C measured by reagents from five manufacturers were compared. Lipemia samples were collected, LDL-C measured using five different reagents were compared. The interference rate was considered unacceptable if it was greater than 1/2 total allowable error (TEa). ResultsIn patients with VitC infusion, the interference rates of TG and total cholesterol (TC) were −59% (−123%, −28%) and −15% (−21%, −11%), respectively. In patients with glycerol fructose infusion, the interference rate of TG was 13% (4%, 113%). LpX interference led to increased LDL-C results for most reagents. Lipemia caused great interference with LDL-C analysis. ConclusionVitC, glycerol fructose, LpX and lipemia significantly interfered with lipid assays. The reagent formulation should be improved to get reliable results.

Маркери психоемоційного стресу у жінок київського регіону в період російсько-української війни

War-related stress (WSR) leads to disruption of vital physiological functions, which can accelerate the development of age-related pathology and early mortality. Therefore, the study of the impact of SPV on the functioning of various body systems requires an in-depth analysis. The purpose of the study is to assess the level of psycho-emotional stress, anxiety, and depression and to investigate their influence on indicators of endothelial function, lipid, carbohydrate metabolism, autonomic nervous regulation of the cardiovascular system) in women of the Kyiv region during the Russian-Ukrainian war. 56 women aged 30-78 were examined (average age - 53.45 ± 1.6 years), who had been in the Kyiv region without permission since the beginning of the Russian-Ukrainian war (February 24, 2022). The control group consisted of 79 women aged 29-85 years, (average age - 56.46 ± 1.44 years), who were examined before the start of the Russian-Ukrainian war in 2018-2021. Anthropometric parameters, fasting plasma glucose level and standard oral glucose tolerance test (OGTT), serum lipid concentration, plasma cortisol level were determined. The function of the endothelium of microvessels was studied by the method of laser Doppler flowmetry in a sample with reactive post-occlusion hyperemia, the state of autonomic regulation of the cardiovascular system by the method of heart rhythm variability analysis. Psychoemotional state using the PLC-5 scale, Beck depression scale, Spielberger-Hanin test, the state of cognitive function was studied using the Montreal Cognitive Assessment (MoCA) A statistically significant increase in the level of cortisol, as an important marker of WSR, was revealed, compared to the control group. Excessive psycho-emotional stress of the body during the war is also evidenced by the predominance of the sympathetic link of autonomous nervous regulation in women. The development of endothelial dysfunction and the negative impact of WSR on lipid and carbohydrate metabolism were confirmed, which was combined with a decrease in mental performance indicators, an increase in the levels of personal and situational anxiety, and depression. An increase in the level of cortisol and the activity of the sympathetic link of the autonomic nervous system indicates the presence of chronic psychoemotional stress, which increases the levels of anxiety and depression, reduces the mental performance of women in war conditions and leads to the development of endothelial dysfunction, disorders of lipid and carbohydrate metabolism.

High dietary energy decreased reproductive performance through increasing lipid deposition in Yangzhou geese at late laying stage

Dietary metabolizable energy (ME) level could offer a well production performance through maintaining lipid homeostasis in poultry. In this study, a total of 540 geese (450 females and 90 males) at 64 wk of age with similar body weight (4,600 ± 382) were randomly divided into 5 groups with 3 replicates in each group and 30 females and 6 males (1♂:5♀) in each replicate. After 2 wk adaptation, the 5 groups were designed to provide diet with ME intakes of 9.65, 10.05, 10.70, 11.45, and 11.75 MJ/kg, respectively, according to production requirement. Body weight, egg production, hatchability, blood lipid, and fat deposition were recorded after 6 wk feeding. The expression of lipid synthesis-related genes, lipoprotein lipase (LPL) and fatty acid synthase (FASN), were determined by quantitative real-time PCR. Geese fed with high ME diet of 11.75 MJ/kg caused an increased liver and abdominal fat weight and low hatchability of set eggs. The ovarian weight and oviduct length were higher in geese fed dietary energy of 10.7 MJ/kg as compared to the 9.65 MJ/kg groups, whereas no significant difference was observed in geese fed dietary energy of 10.05 MJ/kg. Dietary energy level did not change the concentration of serum lipids at the late egg laying stage. The LPL expression exhibited linear and quadratic effect in response to dietary ME. The FASN expression showed quadratic effect and a relatively higher expression was exhibited in 10.05 and 11.45 MJ/kg than that of the 9.65 and 10.70 MJ/kg ME groups. According to the productivity, reproductive performance, and fat deposition, dietary ME of 10.13 to 10.28 MJ/kg could be suggested for breeding geese at their late laying stage.

Associations of breastfeeding duration with serum lipid values from infancy until age 20 years - the STRIP study.

The effect of breastfeeding duration on childhood lipid levels has remained controversial. In this study, we aimed to establish the long-term associations of breastfeeding duration with future levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol. In addition, we report lipid levels at the age of seven months depending on the child receiving any breastmilk. The sample comprised 999 children participating in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP). Serum lipid profile was studied at the ages of seven months and 13 months, and annually thereafter until the age of 20 years. Duration of breastfeeding was inquired, and infants were divided into those who received or did not receive any breast milk at the age of seven months (n=533 and n=466, respectively). In addition, breastfeeding duration groups (any breastfeeding for 0-4 months, 4-6 months, 6-9 months, and >9 months) were formed. At the age of seven months infants who at that time received breast milk had higher serum HDL cholesterol (0.95±0.21mmol/l vs. 0.90±0.19 mmol/l; p=0.0018), non-HDL cholesterol (3.38±0.78 mmol/l vs. 3.01±0.67 mmol/l; p<0.001) and total cholesterol levels (4.33±0.80 mmol/l vs. 3.91±0.69 mmol/l; p<0.001) than their peers who did not receive breast milk. From two to 20 years of age serum lipid levels showed no consistent differences between the breastfeeding duration groups. Our long-term data showed that duration of breastfeeding has no consistent associations with serum lipid concentrations in healthy individuals aged two to 20 years. www.clinicaltrials.gov, unique identifier NCT00223600.

Male Infertility in Patients with Post-Traumatic Stress is Associated with Increased Serum Lipid Concentration

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can occur after experiencing or witnessing life-threatening events such as combat operations, terrorist attacks, accidents or violent physical attacks, rape, etc. Its prevalence is high and it very often occurs in comorbidity with other psychiatric and physical disorders. PTSD patients often exhibit dysregulated lipid metabolic profiles. The aim of the research was to determine the biochemical concentration of lipids (TC, TG, HDL, and LDL) in men with post-traumatic stress disorder, veterans of the war in Kosovo, who are being treated for infertility. Our study included 72 male patients with primary and secondary infertility. Patients with PTSD were permanent residents of the Dukagjin region (the cities of Pejë, Istog, Deçan, Klinë) in the Republic of Kosovo. Serum lipid concentrations were determined on the COBAS INTEGRA 400 plus apparatus. To determine male fertility, we analyzed the parameters of human ejaculation according to the latest manual (6th, WHO 2021). Criteria that must be met to confirm the diagnosis of PTSD. The following instruments were used in the research: ITQ (International Trauma Questionnaire). In patients with PTSD, the mean TC values were higher (6.38 ± 1.20) than the without PTSD group (5.28 ± 0.37) (p=0.018), the concentration of bad cholesterol, LDL was higher in PTSD patients than without PTSD patients (4.16 ± 0.31 vs. 3.65 ± 0.49) (p= 0.016), TG also had higher concentrations (2.43 ± 0.64 ) than without PTSD patients (1.78 ± 0.45), (p = 0.036). HDL in PTSD patients (1.17 ± 0.40) was significantly lower in without PTSD patients (2.47 ± 0.50) (p = 0.021). BMI had no statistically significant differences between the two groups; with PTSD and non-PTSD (26.2 vs 25.6) (p=0.430). In conclusion, biochemical analyzes of the lipid profile of PTSD patients will help clinicians to reduce the possibility of vascular disease in this population during the treatment of male infertility.

Associations between Endothelial Lipase and Apolipoprotein B-Containing Lipoproteins Differ in Healthy Volunteers and Metabolic Syndrome Patients.

The association between serum levels of endothelial lipase (EL) and the serum levels and composition of apolipoprotein B (apoB)-containing lipoproteins in healthy subjects and patients with metabolic syndrome (MS) remained unexplored. Therefore, in the present study, we determined the serum levels and lipid content of apoB-containing lipoproteins using nuclear magnetic resonance (NMR) spectroscopy and examined their association with EL serum levels in healthy volunteers (HVs) and MS patients. EL was significantly negatively correlated with the serum levels of cholesterol in large very low-density lipoprotein (VLDL) particles, as well as with total-cholesterol-, free-cholesterol-, triglyceride-, and phospholipid-contents of VLDL and intermediate-density lipoprotein particles in MS patients but not in HVs. In contrast, EL serum levels were significantly positively correlated with the serum levels of apoB, triglycerides, and phospholipids in large low-density lipoprotein particles in HVs but not in MS patients. EL serum levels as well as the serum levels and lipid content of the majority of apoB-containing lipoprotein subclasses were markedly different in MS patients compared with HVs. We conclude that EL serum levels are associated with the serum levels and lipid content of apoB-containing lipoproteins and that these associations are markedly affected by MS.

Pseudohyponatremia: Mechanism, Diagnosis, Clinical Associations and Management.

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]S, making any inadvertent correction treatment potentially detrimental.

Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside.

High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) ± 400 mg/kg·bw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) ± 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR.

Serum lipids concentration on prognosis of high-grade glioma.

To investigate the effect of serum lipids concentration on the prognosis of high-grade glioma patients undergoing postoperative radiotherapy. Retrospective analysis of the patients with high-grade glioma who received postoperative Intensity Modulated Radiotherapy between 13 May 2013 and 12 September 2018 was performed. The patients were grouped according to the average values of serum total cholesterol, LDL, and HDL concentration in peripheral blood (before surgery, 6months after therapy). Cox proportional hazards model was performed to determine whether the total cholesterol concentration, LDL concentration, and HDL concentration in peripheral blood before therapy and their changes after therapy were factors influencing the prognosis. The results of COX regression analysis showed that the independent prognostic factors of high-grade glioma patients were pathological grade, the extent of resection, serum cholesterol concentration pre-surgery, and the change of LDL concentration from pre-surgery to post-therapy. The prognosis of patients with high serum total cholesterol concentration before therapy was worse than those of patients with low total cholesterol concentration. The 5-year survival rate and the median survival time of patients with high serum total cholesterol concentration before therapy were 4.9% and 23.6months, but the low cholesterol concentration group were 19.6% and 24.5months, respectively. Besides, the average serum LDL concentration in high-grade glioma patients gradually increased after therapy. The 5-year survival rate of patients and the median survival time with elevated LDL concentration after therapy is 11.8% and 20.4months, but the reduced LDL concentration group was 16.7% and 28.4months, respectively. The total cholesterol and LDL concentration increased significantly after therapy in Grade IV patients while Grade III patients did not. The cholesterol concentration before therapy and LDL concentration change from pre-surgery to post-therapy are the factors that affect the prognosis of high-grade glioma patients who have undergone postoperative radiotherapy. In the final analysis, the high serum cholesterol pre-surgery and the increased in serum LDL concentration from pre-surgery to post-therapy were associated with worse survival of patients.

DIABETES MELLITUS AND ASSOCIATED HYPERTENSION, A TOXIC COMBINATION FOR CARDIOVASCULAR RISK

Objective: The coexistence of hypertension in diabetic patients greatly enhances their likelihood of developing CVD. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, inflammation, retinopathy, and “diabetic cardiomyopathy”. We aimed to assess the impact of type 2 diabetes mellitus associated with high blood pressure over these cardiovascular risk factors. Design and method: We performed a transversal study, lasting 12 months, in which 100 patients with essential hypertension, and type 2 diabetes, with medium age 60.7 ± 9.3 years were evaluated in comparison with 100 patients with only hypertension. We evaluate these patients for: BMI; waist circumference; IMT by carotid ultrasonography; microalbuminuria in a spot morning urine; fundus oculi, LVMI for left ventricular hypertrophy by echocardiography. Serum PCR and lipid concentrations were measured. Results: The diabetic hypertensive subjects significantly had higher BMI (p = 0.01) and waist circumference statistically significant (p = 0.005). Patients with hypertension and diabetes had a greater left ventricular mass index (66% vs 51%, P = 0.04). Mean value for IMT was 1.1 ± 0,3 mm for diabetic patients and 0.93 ± 0,2 mm for the other group (P &lt; 0.001) and its prevalence was high in diabetics (75% vs 64%, P = 0.1). Prevalence of microalbuminuria was significantly high in diabetics (44% vs 14%, P &lt; 0.001). PCR as marker of inflammation was prevalently high in people with diabetes and hypertension (32% vs 16%, P = 0.013) Also, prevalence of retinopathy was significantly high in people with diabetes and hypertension compare to other group (27% vs 12%, P = 0.012). There was strong relation between LVMI, microalbuminuria, IMT and PCR. Waist circumference had correlation with IMT and microalbuminuria. Conclusions: DM is an independent risk factor for the increased LV mass and impaired diastolic function regardless of association with hypertension or not. Central obesity is associated with an increased risk for cardio metabolic diseases such as atherosclerosis and diabetic nephropathy. Atherosclerosis is characterized by chronic inflammation affecting the arterial intimae. Thus, individuals with type 2 diabetes and hypertension had increased risk for CVD.

Involvement of glyphosate in disruption of biotransformation P450 enzymes and hepatic lipid metabolism in chicken

The current study investigated the potentially harmful consequences of pure glyphosate or Roundup® on CYP family members and lipid metabolism in newly hatched chicks. On the sixth day, 225 fertilized eggs were randomly divided into three treatments: (1) the control group injected with deionized water, (2) the glyphosate group injected with 10 mg pure glyphosate/Kg egg mass and (3) the Roundup group injected 10 mg the active ingredient glyphosate in Roundup®/Kg egg. The results of the study revealed a reduction in hatchability in chicks treated with Roundup®. Moreover, change of Lipid concentration in serum and the liver-treated groups. Additionally, increased liver function enzymes and increased oxidative stress in the glyphosate and Roundup® groups. Furthermore, liver tissues showed histological changes and several lipid deposits in glyphosate-treated groups. Hepatic CYP1A2 and CYP1A4 expressions were significantly increased (p < .05) after glyphosate exposure, and suppression of CYP1C1 mRNA expression was significant (p < .05) after Roundup® exposure. The pro-inflammatory cytokines genes IFN-γ and IL-1β expression were significantly increased (p < .05) after Roundup® exposure. In addition, there were significant differences in the levels of expression genes which are related to lipid synthesis or catabolism in the liver. In conclusion, in ovo glyphosate exposure caused disruption of biotransformation, pro-inflammatory and lipid metabolism in chicks.

Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

Targeted microbiome metabolomics reveals flaxseed oil supplementation regulated the gut microbiota and farnesoid X receptor pathway in high-fat diet mice

Flaxseed oil (FSO) rich in n-3 polyunsaturated fatty acids (PUFAs) can protect against obesity and insulin resistance, but the underlying mechanism is unknown. An integrative multiomics of the microbiome and targeted metabolomics approach was performed to investigate the possible pathway for flaxseed oil supplementation on reducing serum total cholesterol, triglyceride and epididymal adipose in high-fat diet mice. FSO ameliorated the gut microbial dysbiosis by increasing the community diversity and the abundance of Clostridiales and Ruminococcaceae. These effects were associated with the regulation of bile acid (BAs) in the feces. FSO reduced the concentrations of conjugated BAs, such as cholic acid, tauro-α-murocholic acid, and tauro-ursodesoxycholic acid in feces, which in turn inhibit the intestinal farnesoid X receptor (FXR)-fibroblast growth factor (FGF) 15 signaling pathway. Further analysis revealed that FSO activated FXR in the liver and regulated downstream gene expression (SHP, SREBP-1c, and CPT-1a), which promoted lipolysis and inhibited lipogenesis. The results of this study suggest that FSO modulates serum lipid concentrations by regulating the gut microbiota, FXR-FGF15 signaling and BA metabolism.

Hypolipidemic and insulin sensitizing effects of salsalate beyond suppressing inflammation in a prediabetic rat model.

Background and aims: Low-grade chronic inflammation plays an important role in the pathogenesis of metabolic syndrome, type 2 diabetes and their complications. In this study, we investigated the effects of salsalate, a non-steroidal anti-inflammatory drug, on metabolic disturbances in an animal model of prediabetes-a strain of non-obese hereditary hypertriglyceridemic (HHTg) rats. Materials and Methods: Adult male HHTg and Wistar control rats were fed a standard diet without or with salsalate delivering a daily dose of 200mg/kg of body weight for 6weeks. Tissue sensitivity to insulin action was measured ex vivo according to basal and insulin-stimulated 14C-U-glucose incorporation into muscle glycogen or adipose tissue lipids. The concentration of methylglyoxal and glutathione was determined using the HPLC-method. Gene expression was measured by quantitative RT-PCR. Results: Salsalate treatment of HHTg rats when compared to their untreated controls was associated with significant amelioration of inflammation, dyslipidemia and insulin resistance. Specificaly, salsalate treatment was associated with reduced inflammation, oxidative and dicarbonyl stress when inflammatory markers, lipoperoxidation products and methylglyoxal levels were significantly decreased in serum and tissues. In addition, salsalate ameliorated glycaemia and reduced serum lipid concentrations. Insulin sensitivity in visceral adipose tissue and skeletal muscle was significantly increased after salsalate administration. Further, salsalate markedly reduced hepatic lipid accumulation (triglycerides -29% and cholesterol -14%). Hypolipidemic effects of salsalate were associated with differential expression of genes coding for enzymes and transcription factors involved in lipid synthesis (Fas, Hmgcr), oxidation (Pparα) and transport (Ldlr, Abc transporters), as well as changes in gene expression of cytochrome P450 proteins, in particular decreased Cyp7a and increased Cyp4a isoforms. Conclusion: These results demonstrate important anti-inflammatory and anti-oxidative effects of salsalate that were associated with reduced dyslipidemia and insulin resistance in HHTg rats. Hypolipidemic effects of salsalate were associated with differential expression of genes regulating lipid metabolism in the liver. These results suggest potential beneficial use of salsalate in prediabetic patients with NAFLD symptoms.

Enhanced Hypoglycemic Bioactivity via RAS/Raf-1/MEK/ERK Signaling Pathway by Combining Capsaicin and QUERCETIN from Chili Peppers.

This research work is designed and conducted to explore the joint effect of capsaicin and quercetin and the potential mechanism for the regulation of hyperglycemia. Insulin-resistance HepG2 cell model and high-fat diet combined with streptozotocin-induced type 2 diabetes mouse model are applied for the investigation. The results illustrate that capsaicin and quercetin can exert hypoglycemic effects via reducing the concentrations of serum lipids of total cholesterol, triglyceride and low-density lipoprotein cholesterol, decreasing hepatic enzyme activities of phosphoenolpyruvate, carboxykinase, and glucose-6-phosphatase, as well as improving the histopathological morphology of liver and pancreas tissues. After administration with capsaicin and quercetin, the relative protein expression abundance of Ras, Raf-1, MEK1/2, and ERK1/2 is obviously attenuated compared to diabetic mice. Capsaicin and quercetin at a ratio of 3:1 are generally determined as the optimal combination. Capsaicin and quercetin present in the chili pepper fruit can act in a synergistic way to alleviate hyperglycemia. This study provides supporting data for the discovery of novel anti-diabetic components and for the valorization of chili pepper industry.

Acute insulin response following exercise and its association to lipid changes in sedentary African-American women

Sedentary African-American (AA) women are at increased risk of hypertension, dyslipidemias, metabolic syndrome, and impaired insulin response to exercise. The purpose of the study was to determine the effects of a single bout of aerobic exercise on fasting serum insulin and glucose concentrations following 1464 kJ (350 kcal) of exercise and to determine if this response was associated with serum lipid concentrations in overweight AA women. Premenopausal AA women (n = 11, mean ± SD, age = 32.5 ± 4.8 yr., BMI = 29.8 ± 4.8 kg·m-2, % fat = 35.6 ± 6.3, VO2peak = 21.5 ± 3.6 ml·kg-1·min-1, total cholesterol = 4.8 ± 0.6 mmol·L-1, triglycerides = 0.60 ± 0.2 mmol·L-1, HDLC = 3.3 ± 0.5 mg·dL-1) performed 1464 kJ (350 kcal) of treadmill exercise at 60%-70%VO2peak. Fasting plasma insulin and glucose concentrations were collected 24-h prior to, and immediately, 24-h, and 48 h following exercise. Fasting insulin concentration increased immediately following exercise (Baseline=77.1 ± 10.42 vs. Immediately=117.4 ± 15.28 μU·mL-1, 95%CI= 32.71, 47.89; P&lt;0.05). The change in insulin concentration from 24-h pre- to 24-h post-exercise was correlated with BMI (r= 0.51), VO2peak (r= -0.47), and the change in lipoprotein lipase activity (r=0.37) (P&lt;0.05 for all). In conclusion, in sedentary AA women, the insulin response immediately following exercise may be elevated, and is not suppressed below pre-exercise concentrations during the 48-h following exercise. The insulin response 24-h following exercise is modestly associated with markers of lipoprotein metabolism.

The Effect of the Saffron Intervention on NAFLD Status and Related Gene Expression in a Rat Model.

According to the worldwide increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the present study aimed to investigate the mechanism effects of saffron consumption on preventing NAFLD in a rat model. In an experimental study, 12 rats were randomly divided into 2 groups to be evaluated in the prevention phase for 7 weeks. In the prevention phase, the animals were randomly assigned to either fed HFHS + 250 mg/kg saffron (S) or fed with HFHS. Afterward, parts of the liver were excised for histopathologic examination. Plasma concentrations of ALT, AST, GGT, ALP, serum lipids, insulin concentrations, plasma glucose, hs-CRP, and TAC were measured. Moreover, Also, the gene expression of 6 target genes was evaluated, including FAS, ACC1, CPT1 ،PPARα ،DGAT2, and SREBP 1-c at the beginning and end of the study. Also, the differences among groups were evaluated by the Mann-Whitney test for non-normal data and the independent t test for normal data. The prevention phase groups have a significant elevation in body weight ( P = 0.034) and food intake (P = 0.001) of the HFHS group versus HFHS + 250 mg/kg S group. Also, there was a significant difference between groups 1 and 2 for ALT (P = 0.011) and AST (P = 0.010), and TG (P = 0.040). The HFHS group had higher plasma levels of FBS (P = 0.001), insulin (P = 0.035), HOMA-IR (P = 0.032), and lower TAC (P = 0.041) versus the HFHS+ S group. Also, the difference between HFHS + 250 mg/kg S and HFHS for PPARα gene expression was significant (P = 0.030). The present study showed that consumption of saffron could prevent developing NAFLD in rats at least partially through modulation in gene expression of PPARα.