Reduced Lipid Levels Research Articles

Efficacy and adverse reaction to different doses of atorvastatin in the treatment of type II diabetes mellitus

Background: Type II diabetes mellitus (T2DM), a persistent metabolic disorder, is primarily characterized by insulin resistance, relative insulin deficiency and dyslipidemia. Here, we aimed to investigate whether different doses of atorvastatin (ATV) affect rats with T2DM. A total of 110 Sprague–Dawley rats were successfully established as T2DM models. Methods: First, the total cholesterol, triglyceride (TG), high-/low-/very-low-density lipoprotein cholesterol (HDL-c/LDL-c/VLDL-c), alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), apolipoprotein Al (ApoA1) and apolipoprotein B (ApoB) levels in rat serum were analyzed. In addition, cholesteryl ester transfer protein (CETP) and retinol-binding protein 4 (RBP4) were also measured. Then, the incidence of adverse reactions was noted. Finally, the pathological study of liver and pancreatic tissues was performed. Results: Rats administered ATV at the doses of 40 and 80 mg/(kg·day) showed down-regulated TG, LDL-c, ApoB, CETP and RBP4 levels yet up-regulated HDL-c and ApoAl levels. Rats administered ATV at a dose of 80 mg/(kg·day) exhibited a higher incidence of adverse reactions and higher ALT and AST levels but lower BUN and Cr levels, which might affect liver and kidney function. Rats administered ATV at the doses of 40 and 80 mg/(kg·day) demonstrated significantly improved liver injury and pancreatic injury induced by T2DM. Conclusion: These data revealed that ATV could improve the lipid metabolism in T2DM rats and 40 mg/(kg·day) may serve as the optimal dose for the reduction of lipid levels and the incidence of adverse effects.

FAX2 Mediates Fatty Acid Export from Plastids in Developing Arabidopsis Seeds.

Vegetable oils are mainly stored in the form of triacylglycerol (TAG) in oilseeds. Fatty acids (FAs), one of the building blocks for TAG assembly, are synthesized in plastids and then exported to the endoplasmic reticulum for storage oil synthesis. A recent study demonstrated that the export of FAs from plastids was mediated by a FAX (FA export) family protein. However, the significance of FAs export from plastid during seed oil accumulation has not been investigated. In this study, we found that FAX2 was highly expressed in developing Arabidopsis seeds and the expression level was consistent with FAs synthesis activity. FAX2 mutant seeds showed an approximately 18% reduction of lipid levels compared with wild-type seeds. By contrast, overexpression of FAX2 enhanced seed lipid accumulation by up to 30%. The FAs export activity of FAX2 was confirmed by yeast mutant cell complementation analysis. Our results showed that FAX2 could interact with other proteins to facilitate FAs transport. Taken together, these results indicate that FAX2-mediated FA export from plastids is important for seed oil accumulation, and that FAX2 can be used as a target gene for increasing lipid production in oilseeds.

Effect of 5-year continuous positive airway pressure treatment on the lipid profile of patients with obstructive sleep apnea: A pilot study.

Continuous positive airway pressure (CPAP) provides a well-documented symptomatic relief for most patients with obstructive sleep apnea (OSA); however, its effect on dyslipidaemia remains contradictory. The aim of this longitudinal pilot study was to investigate the effect of long-term CPAP treatment on the lipid profile of patients with severe OSA. Fasting serum levels of total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride (TG) were longitudinally measured in 33 OSA patients with an apnea-hypopnea index (AHI) of ≥30 events/hr, at the time of diagnosis (baseline) and at control visits following fixed-pressure CPAP treatment. Compared to baseline values, even as short as a 2-month CPAP therapy resulted in a significant decrease of both TC and LDL-C levels (TC, 5.62±0.22 vs. 5.18±0.21mmol/L; LDL-C, 3.52±0.19 vs. 3.19±0.2mmol/L; p<0.05 for each). These lipid fractions exhibited similar improvements at 6months and after 5years of CPAP treatment (TC, 5.1±0.17mmol/L; LDL-C, 2.86±0.16mmol/L; p<0.01 for each). The reduction in lipid levels was greater in younger patients and/or in those who had higher body mass index (BMI) (p<0.05). There were no significant correlations between AHI and lipid levels (p>0.05); BMI showed a weak negative association with HDL-C fraction (BMI, r=-0.263, p<0.05). CPAP therapy had neither short- nor long-term effects on TG and HDL-C levels (p>0.05). CPAP therapy has a rapid and long-lasting beneficial effect on the lipid profile of patients with severe OSA.

Acteoside From Ligustrum robustum (Roxb.) Blume Ameliorates Lipid Metabolism and Synthesis in a HepG2 Cell Model of Lipid Accumulation.

We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha (bitter tea), have long been used in China as an herbal tea for weight loss. Recently, based on previous studies, our team reached a preliminary conclusion that phenylpropanoid glycosides from L. robustum most likely contribute substantially to reducing lipid levels, but the mechanism remains unclear. Here, we conducted an in silico screen of currently known phenylethanoid glycosides from L. robustum and attempted to explore the hypolipidemic mechanism of ACT, the representative component of phenylethanoid glycosides in L. robustum, using RNA-seq technology, quantitative real-time PCR (qPCR) and Western blotting. First, the screening results for six compounds were docked with 15 human protein targets, and 3 of 15 protein targets were related to cardiovascular diseases. Based on previous experimental data and docking results, we selected ACT, which exerted positive effects, for further study. We generated a lipid accumulation model using HepG2 cells treated with a high concentration of oleic acid and then extracted RNA from cells treated for 24 h with 50 μmol/L ACT. Subsequently, we performed a transcriptomic analysis of the RNA-seq results, which revealed a large number of differentially expressed genes. Finally, we randomly selected some genes and proteins for further validation using qPCR and Western blotting; the results agreed with the RNA-seq data and confirmed their reliability. In conclusion, our experiments proved that ACT from L. robustum alters lipid metabolism and synthesis by regulating the expression of multiple genes, including Scarb1, Scarb2, Srebf1, Dhcr7, Acat2, Hmgcr, Fdft1, and Lss, which are involved several pathways, such as the glycolytic, AMPK, and fatty acid degradation pathways.

Anti-Adipogenic Effects of Delphinidin-3-O-β-Glucoside in 3T3-L1 Preadipocytes and Primary White Adipocytes.

Delphinidin-3-O-β-glucoside (D3G) is a health-promoting anthocyanin whose anti-obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on adipogenesis and lipogenesis in 3T3-L1 adipocytes and primary white adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 adipocytes, D3G downregulated the expression of key adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in adipocytes. Our data indicate that D3G attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of obesity.

Treatment of Therapy-Resistant Hyperlipidaemia after Heart Transplant with PCSK9-Inhibitors

Purpose Hyperlipidemia is a major factor in the development of graft vasculopathy (GVP) after heart transplant. The incidence of hyperlipidaemia in heart transplant (HTX) patients under immunosuppressive therapy is 74% in the first year, and 91% in the first five years. Lipid-lowering therapy with statins presents a great challenge due to interactions and adverse effects. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have already proven very effective in high-risk cardiovascular patients. In our centre, PCSK9-inhibitors have been administered to selected HTX-patients, in which the target LDL-Cholesterol of 100mg/dl could not be reached with reasonable doses of statins and/or Etizimib. Methods In the period 02/2017 to 06/2018, 15 adult HTX-patients (median age 55.3, (25-75%: 48.2-64.6), 25% female) were selected. The patients were at a median of 35.1 (25-75%: 28.4-78.6) months post-HTX. The selected patients were evaluated together in the lipid clinic (licenced for PCSK9-inhibitors). Therapy was initiated with Alirocumab 75mg. Statin-therapy was changed and appropriately documented when changes in lipid-parameters and/or adverse effects occurred. In order to evaluate incidence and prevalence of myopathy and hepatotoxicity, CK and liver enzymes and were measured 1, 3, 6, 9, 12, and 15 months post conversion. Analysis of effectiveness were conducted by measuring blood lipids (LDL-C, HDL, total cholesterol, triglycerides, and LP(a)). Results Total cholesterol (231 (198-245) vs. 151 (139-175) mg/dl; p Conclusion Therapy with PCSK9-inhibitors (Alirocumab) constitutes an effective and safe option in therapy of hyperlipidaemia after heart transplant. Under treatment liver and kidney parameters stayed stable, while a significant reduction of lipid levels could be achieved. To evaluate the long-term effects of PCSK9-Inhibitors longer observation period is necessary.

Chlorogenic acid alleviates obesity and modulates gut microbiota in high-fat-fed mice.

To evaluate the anti‐obesity effects of chlorogenic acid (CGA), the mice were fed a high‐fat diet (HFD) upon chlorogenic acid treatment for 6 weeks. The results showed administration of chlorogenic acid (150 mg per kg per day) remarkably promoted body loss, reduced lipid levels in plasma and altered mRNA expression of lipogenesis and lipolysis related genes in adipose tissue. Moreover, chlorogenic acid also reversed the HFD‐induced gut microbiota dysbiosis, including significantly inhibiting the growth of Desulfovibrionaceae, Ruminococcaceae, Lachnospiraceae, Erysipelotrichaceae, and raising the growth of Bacteroidaceae, Lactobacillaceae. Overall, the amelioration of HFD‐induced gut microbiota dysbiosis by chlorogenic acid may contribute, at least partially, to its beneficial effects on ameliorating HFD‐induced obesity.

Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice

Atherosclerosis (AS) is the common pathological basis of chronic cardiovascular diseases and is associated with inflammation and lipid metabolism dysfunction. Geniposide, the main active ingredient of Gardenia jasminoides Ellis fruit, exhibits a variety of anti-inflammatory and anti-oxidative functions; however, its role in AS remains unclear. The aim of this study was to investigate the mechanisms of geniposide in alleviating inflammation and thereby attenuating the development of AS. ApoE−/− mice were fed a high fat diet to induce AS and were treated with geniposide (50 mg/kg) for 12 weeks. Blood glucose and lipid levels were measured by biochemical analysis. H&E, Masson and Oil red O staining were performed to observe morphological changes and lipid deposition in the aorta and liver. Serum inflammatory cytokines were detected by ELISA. Dual-luciferase reporter gene assay was used to verify the target relationship between microRNA-101 (miR-101) and mitogen-activated protein kinase phosphatase-1 (MKP-1). The levels of miR-101, p-p38, and MKP-1 in the aorta were detected by qPCR and western blotting. The anti-inflammatory effect of geniposide in vitro was investigated in the RAW264.7 macrophage cell line. A miR-101 mimic and an inhibitor were used to study the effect of miR-101 on regulating the expression of the target MKP-1 and the downstream inflammatory cytokines. Geniposide treatment reduced lipid levels and plaque size in the mouse model of AS. Geniposide downregulated miR-101 to upregulate MKP-1 and suppress the production of inflammatory factors in vitro and in vivo. Geniposide suppressed the levels of inflammatory factors in the presence of the miR-101 mimic, whereas no obvious effect was observed in the miR-101 inhibitor group. We concluded that geniposide reduced the plaque size and alleviated inflammatory injury in ApoE−/− mice and RAW264.7 cells. The specific anti-inflammatory mechanism was related to the miR-101/ MKP-1/p38 signaling pathway.

A Systematic Review of Medication Adherence Thresholds Dependent of Clinical Outcomes.

Background: In pharmacotherapy, the achievement of a target clinical outcome requires a certain level of medication intake or adherence. Based on Haynes's early empirical definition of sufficient adherence to antihypertensive medications as taking ≥80% of medication, many researchers used this threshold to distinguish adherent from non-adherent patients. However, we propose that different diseases, medications and patient's characteristics influence the cut-off point of the adherence rate above which the clinical outcome is satisfactory (thereafter medication adherence threshold). Moreover, the assessment of adherence and clinical outcomes may differ greatly and should be taken into consideration. To our knowledge, very few studies have defined adherence rates linked to clinical outcomes. We aimed at investigating medication adherence thresholds in relation to clinical outcomes.Method: We searched for studies that determined the relationship between adherence rates and clinical outcomes in the databases PubMed, EmbaseⓇ and Web of Science™ until December 2017, limited to English-language. Our outcome measure was any threshold value of adherence. The inclusion criteria of the retrieved studies were (1) any measurement of medication adherence, (2) any assessment of clinical outcomes, and (3) any method to define medication adherence thresholds in relation to clinical outcomes. We excluded articles considered as a tutorial. Two authors (PB and IA) independently screened titles and abstracts for relevance, reviewed full-texts, and extracted items. The results of the included studies are presented qualitatively.Result: We analyzed 6 articles that assessed clinical outcomes linked to adherence rates in 7 chronic disease states. Medication adherence was measured with Medication Possession Ratio (MPR, n = 3), Proportion of Days Covered (PDC, n = 1), both (n = 1), or Medication Event Monitoring System (MEMS). Clinical outcomes were event free episodes, hospitalization, cortisone use, reported symptoms and reduction of lipid levels. To find the relationship between the targeted clinical outcome and adherence rates, three studies applied logistic regression and three used survival analysis. Five studies defined adherence thresholds between 46 and 92%. One study confirmed the 80% threshold as valid to distinguish adherent from non-adherent patients.Conclusion: The analyzed studies were highly heterogeneous, predominantly concerning methods of calculating adherence. We could not compare studies quantitatively, mostly because adherence rates could not be standardized. Therefore, we cannot reject or confirm the validity of the historical 80% threshold. Nevertheless, the 80% threshold was clearly questioned as a general standard.

Effects of sanshoamides and capsaicinoids on plasma and liver lipid metabolism in hyperlipidemic rats.

The objective of this study was to determine the effects of sanshoamides and capsaiciniods on plasma and liver lipid levels and the mRNA expression levels of key receptors involved in cholesterol metabolism in hyperlipidemic rats. A total of 56 three-week-old female Sprague-Dawley rats were assigned to 7 treatment groups based on initial body weight (n = 8 rats per group). With certain combinations of sanshoamides and capsaicinoids significantly increased food intake, reduced lipid levels in blood and liver, improved histological characteristics of a fatty liver, down regulated mRNA expression levels of cholesterol 7-alpha-hydroxylase (CYP7A1), 3-hydroxyl-3-methylglutary CoA (HMG-CoA) and Farnesoid X Receptor (FXR) in liver and apical sodium-dependent bile acid transporter, Ileal Bile Acid Binding Protein and FXR in the ileum in hyperlipidemic rats. These results indicated that dietary supplementation with sanshoamides and capsaicinoids reduced blood lipid levels and improved cholesterol metabolism in hyperlipidemic rats.

Fermentation improves the potentiality of capsicum in decreasing high-fat diet-induced obesity in C57BL/6 mice by modulating lipid metabolism and hormone response.

Capsicum has been proved to have anti-obesity effect. In this study, extracts from multi-strain coupled fermented capsicum (EFC) and from fresh capsicum (EC) were compared in their anti-obesity effect among these obese mice induced by high-fat diet (HFD), in order to exploring the potential mechanism of EFC for alleviating obesity. It has shown that the constituents of capsicum undergo transformation during fermentation. Obese mice in all experimental groups had similar energy absorption, and both EFC and EC relieved obesity, with better effect in the EFC group than in the EC group. Lower lipid and cholesterol were observed in serum, liver and feces in HFD-FC (HFD supplied with EFC)group compared to HFD-C (HFD supplied with EC) group. In addition, the HFD-FC group had less visceral fat and a smaller adipocyte size. The HFD-FC group exhibited better sensitivity to hormones, with lower levels of both leptin and insulin and higher ghrelin level. Expression of PPARα, CPT-1α, HSL and ACO were up-regulated, whereas PPARγ and C/EBPα were down-regulated significantly in the HFD-FC group compared to the HFD-C group. In summary, fermentation of Capsicum leads to a better effect on preventing fat accumulation and reducing lipid levels, which may be regulated by certain new contents in EFC that facilitate lipid metabolism and hormone response.

Overfed mice got rhythm

Metabolic Disease Metabolic health is intertwined with the body's circadian clock, but the mechanisms underlying this connection are not fully understood. Studying mice, Guan et al. examined the effect of diet-induced obesity on circadian expression of genes in the liver. They found that obesity intensifies and synchronizes the liver circadian rhythms of enhancers that control the expression of two transcription factors with opposing effects on lipid metabolism. The result is enhanced synthesis and oxidation of fatty acids. Drugs activating one of these transcription factors, PPARα, are already used clinically to reduce lipid levels. Interestingly, in obese mice, these drugs were most effective when delivered at peak PPARα expression, indicating that their efficacy in humans might be optimized by administration at certain times of day. Cell 174 , 831 (2018).

Dietary Intake of Curcumin Improves eIF2 Signaling and Reduces Lipid Levels in the White Adipose Tissue of Obese Mice

White adipose tissue (eWAT) plays a crucial role in preventing metabolic syndrome. We aimed to investigate WAT distribution and gene expression and lipidomic profiles in epididymal WAT (eWAT) in diet-induced obese mice, reflecting a Western-style diet of humans to elucidate the bioactive properties of the dietary antioxidant curcumin in preventing lifestyle-related diseases. For 16 weeks, we fed C57BL/6J mice with a control diet, a high-fat, high-sucrose and high-cholesterol Western diet or Western diet supplemented with 0.1% (w/w) curcumin. Although the dietary intake of curcumin did not affect eWAT weight or plasma lipid levels, it reduced lipid peroxidation markers’ levels in eWAT. Curcumin accumulated in eWAT and changed gene expressions related to eukaryotic translation initiation factor 2 (eIF2) signalling. Curcumin suppressed eIF2α phosphorylation, which is induced by endoplasmic reticulum (ER) stress, macrophage accumulation and nuclear factor-κB (NF-κB) p65 and leptin expression, whereas it’s anti-inflammatory effect was inadequate to decrease TNF-α and IFN-γ levels. Lipidomic and gene expression analysis revealed that curcumin decreased some diacylglycerols (DAGs) and DAG-derived glycerophospholipids levels by suppressing the glycerol-3-phosphate acyltransferase 1 and adipose triglyceride lipase expression, which are associated with lipogenesis and lipolysis, respectively. Presumably, these intertwined effects contribute to metabolic syndrome prevention by dietary modification.

Qing brick tea (QBT) aqueous extract protects monosodium glutamate-induced obese mice against metabolic syndrome and involves up-regulation Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) antioxidant pathway

BackgroundQing brick tea (QBT), traditional and popular beverage for Chinese people, is an important post-fermentation dark tea. Our present study was performed to investigate the ameliorative effects of QBT aqueous extract on metabolic syndrome (Mets) in monosodium glutamate-induced obese mice and the potential mechanisms. MethodMonosodium glutamate-induced obese mice were used to evaluate the anti-Mets effects of QBT. Content levels of malonaldehyde (MDA), reactive oxygen species (ROS) and protein carbonylation, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) in the skeletal muscle were assessed by commercial kits, respectively. Western blot and Q-PCR were used to detect the expressions of Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) signaling pathway and downstream antioxidant factors. In addition, activity of AKT signaling and expression of glucose transporter type 4 (GLUT4) in the skeletal muscle were investigated by western blot. ResultQBT treatment limited gain of body weight, waistline and LEE index, improved insulin resistance and glucose intolerance, reduced lipid level in MSG mice. Content levels of MDA, ROS and protein carbonylation in skeletal muscle of QBT group were significantly improved compared to those of MSG mice. The antioxidant enzyme activities of SOD, GPx, CAT, and GR were increased in skeletal muscle of MSG mice intervened with QBT. After 20-week QBT treatment, Nrf2 signaling pathway and downstream antioxidant factors were both increased in the skeletal muscle. In addition, QBT treatment improved insulin signaling by preferentially augmenting AKT signaling, as well as increased the protein expression of GLUT4 in the skeletal muscle. ConclusionOur results showed that QBT intake was effective in protecting monosodium glutamate-induced obese mice against metabolic syndrome and involved in the Nrf2 signaling pathway in the skeletal muscle.

S19. EVIDENCE OF THE LIPID PARADOX IN PSYCHOSIS: A META-ANALYSIS OF CHOLESTEROL AND TRIGLYCERIDE LEVELS IN FIRST EPISODE PSYCHOSIS

BackgroundUntreated, active rheumatoid arthritis is associated with reduced total and lowdensity lipoprotein (LDL) cholesterol. Despite this apparently favorable lipid profile, these patients are at elevated risk of cardiovascular disease, with the association therefore referred to as the ‘lipid paradox’. The mechanism underlying low total and LDL cholesterol in rheumatoid arthritis is considered to be driven by inflammatory cytokines. IL-6 reduces lipid levels in animal models, and treatment of rheumatoid arthritis with anti-IL-6 and anti-TNFalpha monoclonal antibodies is associated with an increase in total and LDL cholesterol. First episode psychosis (FEP) is associated with elevated levels of these same inflammatory cytokines, thus a similar mechanism underlying lipid abnormalities may exist. This study set out to clarify the lipid status of antipsychotic naive/minimally treated FEP, testing the hypothesis that if psychosis is deemed to be an inflammatory condition, then a serological metabolic signature characterized by reduced total and LDL cholesterol should be observed.MethodsA meta-analysis of studies examining lipid parameters in individuals with FEP and no or minimal antipsychotic exposure versus a healthy control group was performed. Studies reported fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and leptin levels.ResultsOf 2070 citations retrieved, 20 case–control studies met inclusion criteria including 1167 patients and 1184 controls. Total cholesterol and LDL cholesterol levels were significantly decreased in patients compared with controls, corresponding to an absolute reduction of 0.26 mmol/L (p = 0.005) and 0.15 mmol/L (p = 0.001) respectively. These findings remained in BMI-matched sensitivity analyses. Triglyceride levels were significantly increased in the patient group, corresponding to an absolute increase of 0.08 mmol/L (p = 0.02). However, HDL cholesterol and leptin levels were not altered in patients compared with controls.DiscussionTotal and LDL cholesterol levels are reduced in FEP, findings which persist in BMI-matched sensitivity analyses. This metabolic signature, combined with elevated insulin resistance that we have previously demonstrated in FEP, mirrors metabolic outcomes observed in pro-inflammatory conditions such as rheumatoid arthritis. FEP is associated with raised levels of multiple pro-inflammatory mediators, which include the adipocytokines IL6 and TNFalpha. IL6 is associated with a reduction in cholesterol in pre-clinical models, thus the mechanism underlying low cholesterol in FEP could be driven by a pro-inflammatory state, and the lipid paradox of rheumatoid arthritis may be present in FEP. These findings also indicate that hypercholesterolemia in patients with chronic schizophrenia is secondary and potentially modifiable. In contrast, triglycerides are elevated in FEP. Hypertriglyceridemia is a feature of type 2 diabetes mellitus, therefore this finding adds to the evidence for glucose dysregulation in this cohort.

Folic acid delays development of atherosclerosis in low-density lipoprotein receptor-deficient mice.

Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low‐density lipoprotein receptor‐deficient (LDLR−/−) mice and to elucidate the molecular processes underlying this effect. LDLR−/− mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α‐actin (α‐SMA) antibodies and anti‐osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α‐SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high‐fat‐fed LDLR−/− mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Statin medications, most commonly prescribed to reduce lipid levels and prevent cardiovascular disease, may be associated with longer survival times of patients with cancer. However, the association of statins with outcomes of patients with pancreatic adenocarcinoma is not clear. We analyzed the association of statin use before a diagnosis of pancreatic cancer with survival times of 648 participants in the Nurses' Health Study and Health Professionals Follow-up Study who were diagnosed with pancreatic adenocarcinoma from 2000 through 2013. We estimated hazard ratios (HRs) for overall mortality using Cox proportional hazards models with adjustment for potential confounders. We assessed the temporal association between prediagnosis statin use and cancer survival by 2-year lag periods to account for a possible latency period between statin use and cancer survival. Regular statin use before diagnosis of pancreatic cancer was associated with modestly prolonged survival compared with nonregular use (adjusted HR, 0.82; 95% CI, 0.69-0.97; P= .02). A 1-month longer median survival was observed in regular statin users compared with nonregular users. Regular statin use within the 2 years prior to cancer diagnosis was most strongly associated with longer survival. We observed no statistically significant effect modification by smoking status, body mass index, diabetes, or cancer stage (all Pinteraction > .53). Regular statin use before diagnosis was similarly associated with survival in the Nurses' Health Study (HR, 0.79; 95% CI, 0.64-0.97) and Health Professionals Follow-up Study (HR, 0.86; 95% CI, 0.63-1.15). Regular statin use before diagnosis of pancreatic cancer was associated with modest increases in survival times in 2 large prospective cohort studies.

Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis - Systematic Review.

Background and Aims: Hypercholesterolemia is a common finding in patients with primary biliary cholangitis (PBC) and is a well-defined risk factor for cardiovascular disease. However, studies have been mixed on whether PBC patients do, in fact, have higher cardiovascular risk. The aim of this study is to review the current literature and provide an evidence-based assessment of cardiovascular risk in PBC patients.Methods: We performed a systematic literature search on PubMed regarding patients with PBC and cardiovascular events from the database inception to July 1, 2017. A total of 33 articles fulfilling our inclusion criteria were found.Results: The majority of the studies evaluated yielded no statistically significant difference in cardiovascular disease in the PBC population compared to the general public. However, some reports found a statistically significantly increase in coronary artery disease. Several studies have looked at the specific lipid profile of patients with PBC with hypocholesteremia. While these lipid abnormalities differ by stage of disease, there is evidence to suggest that the specific lipid profile in PBC may have lower atherogenicity than in patients with hypercholesterolemia without PBC. Studies looking at patients with PBC with other risk factors for cardiovascular disease, such as hypertension and metabolic syndrome, have consistently found a higher risk for cardiovascular disease in these patients. Statin treatment is effective in reducing lipid levels and possibly improving endothelial inflammation in patients with PBC with hypercholesterolemia.Conclusions: There is not enough evidence to suggest an increased risk of cardiovascular disease in patients with PBC with hypercholesterolemia, except for those individuals with concomitant features of metabolic syndrome. In patients with PBC with no additional cardiovascular risk factors, individual risk/benefit discussion on lipid-lowering treatment should be considered.

The effect of melatonin on the lipid levels in menopausal women: A double-blind, controlled, clinical trial.

BACKGROUND:Cardiovascular diseases are the major public health problem in many countries and are responsible for more than half of the deaths in above 50-year-old women. The most common curable risk factor of these disorders is hypoestrogenemia resulting from menopause. The present study aimed to investigate the effect of melatonin on plasma lipid levels in menopausal women.MATERIALS AND METHODS:The present double-blind, placebo-controlled, clinical trial was conducted in 2013–2014 on 240 menopausal women between 40 and 60 years old referring to the Gynecology and obstetrics clinics of Shiraz University of Medical Sciences who were randomly divided into two groups. The intervention group received 3 mg melatonin tablets and the control group received the placebo for 3 months. The data were gathered using the demographic information questionnaire and lipid profile test before and 3 months after the intervention. Then, the data were analyzed through the SPSS statistical software (version 16). The repeated measures analysis of variance, the least significant difference, the independent-sample t, the Chi-square, and Fisher's exact tests were done for data analysis.RESULTS:The two study groups were similar regarding the demographic and clinical variables at the beginning of the study. In the melatonin group, the amount of triglyceride increased from 140.34 ± 48.29 before the study to 151.24 ± 54.60 3 months after the intervention and no significant difference was observed between the two groups in this regard (confidence interval [CI] = 95%, P > 0.05). In addition, no significant difference was found between the two groups concerning low-density lipoprotein cholesterol level (CI = 95%, P = 0.125).CONCLUSION:Melatonin was not effective in reduction of lipid levels. However, further controlled studies are needed to be conducted on the issue.

Blackspot seabream (Pagellus bogaraveo) fed different diets. Histologic study of the lipid muscle fiber distribution and effect on quality during shelf life

To determine differences between commercial size wild and farmed blackspot seabream, some parameters affecting quality were evaluated during shelf life, namely the fatty acid profiles, pH, muscle colour and Quality Index Method (QIM). In addition, a histological study of the lipids' distribution in the myotome (slow or fast twitch) in different dorsal areas was performed. In farmed fish, three diets were tested. One of them was a commercial diet formulated with a high proportion of lipids, mostly from fish oil. The other two diets were formulated with reduced lipid levels by 60%. In one (low lipid diet, LL) the proportions of protein sources were maintained and in the other (low lipid diet+fish meal, LL+) most of the protein was provided as fish meal.Lipid depots were not found to be different in the myocytes of the fast-twitch fibers. However, regional differences were identified in the slow-twitch fibers depending on the area and the diet, whether in the cranial, medial or caudal portion of the dorsal myotome. The worst scores of the QIM were recorded for the Control diet and the wild fish group. In addition, QIM showed a positive correlation with total n-3 and a negative with other lipid fractions. The a* values in skin and the chroma in muscle of the wild fish were superior to those measured in farmed fish. Fish fed the LL+ diet had higher fillet protein content than that of the wild counterpart. As for nutritional value, farmed fish were able to deposit more DHA than was offered in all experimental diets used, especially with the LL+ diet which yielded threefold more DHA.