Plasma Low-density Lipoprotein Concentrations Research Articles

Importance of the detection of genetic diseases associated with cardiovascular risk in pediatric age

Familial Hypercholesterolemia (FH) is a disease with a homozygous or heterozygous autosomal dominant inheritance pattern. It is characterized by high plasma concentrations of Low-Density Lipoprotein (LDL) cholesterol

Development of Direct LDL Measurement by LDL Precipitation Combined with Sandwich ELISA Using In-House-Generated mAbs.

One of the major risk factors for the progression of cardiovascular diseases is a high blood level of low-density lipoprotein (LDL), so progression of the disease may be prevented by lowering the plasma LDL. Evaluation and monitoring of LDL concentrations are therefore necessary. Friedewald's equation is a calculation method that is currently used routinely to estimate plasma LDL concentrations in hospital laboratories. However, this method cannot be applied to samples with a high concentration of triglyceride (TG). To overcome this limitation, this study aimed to develop direct LDL measurements using in-house generated monoclonal antibodies against human LDL in combination with LDL precipitation using heparin-containing citrate buffer pH 5.04. The method was applied to measure the LDL concentration in 208 randomized samples from Suranaree University of Technology Hospital. The mean values obtained from the developed method and the hospital laboratory were 126.6 ± 43.1 mg/dL and 123.2 ± 42.3 mg/dL, respectively. Linear regression analysis showed a high correlation between these two methods (r = 0.8491, p < 0.0001). High concentrations of TG, total cholesterol, and HDL have no influence on the LDL values obtained by this method. In this study, we offer an alternative technique for the direct measurement of plasma LDL. Further development for more convenient and easy use can now be undertaken.

Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association

Abstractvon Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association. Vortexing VWF in tubes resulted in its loss from the solution and deposition onto tube surfaces, which was prevented by HDL. At a stabilizing HDL concentration of 1.2 mg/mL, increasing concentrations of LDL progressively increased VWF loss, the effect correlating with the LDL-to-HDL ratio and not the absolute concentration of the lipoproteins. Similarly, HDL diminished deposition of VWF in a post-in-channel microfluidic device, whereas LDL increased both the rate and extent of strand deposition, with both purified VWF and plasma. Hypercholesterolemic human plasma also displayed accelerated VWF accumulation in the microfluidic device. The initial rate of accumulation correlated linearly with the LDL-to-HDL ratio. In Adamts13−/− and Adamts13−/−LDLR−/− mice, high LDL levels enhanced VWF and platelet adhesion to the myocardial microvasculature, reducing cardiac perfusion, impairing systolic function, and producing early signs of cardiomyopathy. In wild-type mice, high plasma LDL concentrations also increased the size and persistence of VWF-platelet thrombi in ionophore-treated mesenteric microvessels, exceeding the accumulation seen in similarly treated ADAMTS13-deficient mice that did not receive LDL infusion. We propose that targeting the interaction of VWF with itself and with LDL may improve the course of thrombotic microangiopathies, atherosclerosis, and other disorders with defective microvascular circulation.

Novel protein-truncating variant in the APOB gene may protect from coronary artery disease and adverse cardiovascular events

Background and aimsGenetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon. MethodsStarting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol. ResultsAPOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-100 (ApoB-51), with a truncation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-48, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation. ConclusionsOur data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes.

Lipid Profile of the Patient with Acute Coronary Syndromes Undergoing Coronary Angiography (CAG) in Rural Costal Region of Maharashtra

Background: Coronary Heart Disease (CHD) is widely prevalent across the globe and significantly high level of Cholesterol in circulation is a single major risk factor associated with coronary heart disease. It is well established that cardiovascular disease is associated with hypertension and elevated blood levels of low-density lipoprotein (LDL), total cholesterol, and triglycerides. In disparity, a low level of high-density lipoprotein (HDL) is a risk factor for mortality from cardiovascular disease. Aim: The present study was conducted with the aim to assess the lipid profile in patients of Acute Coronary Syndrome (ACS) undergoing coronary angiography (CAG) in rural coastal population. Patients and Methods: The present study was done on 62 patients with Acute Coronary Syndrome (ACS) undergoing coronary angiography (CAG) Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were examined in biochemical laboratory of the hospital. Coronary angiography was performed for the presence of lesions. Results: 43.5% of the patients (n=27) were elderly (age&gt;60 years). Approximately 82% of the patients (n=51) aged more than 50 years. Males outnumbered females with a ratio of 2.4:1. 71% of the patients were males. Mean cholesterol levels were 177.86 mg/dl. Approx 3/4th of the patients (n=41) had cholesterol level &lt;200 mg/Dl. Mean triglycerides levels in the patients were 158.29 mg/dl. Only 11 patients out of 62 CAD patients had abnormal triglycerides. Mean LDL level was 119.5 mg and Mean HDL level was 34.5 mg %. The high plasma concentration of low-density lipoprotein (LDL-C) in 30% and the low plasma concentration of high-density lipoprotein (HDL-C) n 33% of patients were important abnormal findings in our patients. Conclusion: Dyslipidemia as in form of very low levels of HDL cholesterol with comparatively high levels of LDL-c with near normal total Cholesterol and triglyceride levels associated with ACS in our rural costal region of Maharashtra.

Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD.

Abstract 14133: Hepatic Deletion of the Cargo Receptor Surf4 Causes Marked Hypocholesterolemia in Mice

Introduction: High plasma concentration of low-density lipoprotein (LDL) is a strong risk factor for coronary artery diseases. Circulating LDL level is a balance between the secretion of its precursor, very low-density lipoprotein (VLDL), and LDL uptake by tissues. Central to these processes are the secretion of APOB - a protein component of VLDL, and PCSK9 - a negative regulator of LDL uptake. We previously demonstrated that the cargo receptor SURF4 mediates the secretion of PCSK9 heterologously expressed in HEK293T cells. We now report the generation and characterization of hepatocyte-specific Surf4 knockout ( Surf4 LKO ) mice. Methods and Results: Hepatic deletion of Surf4 results in a marked reduction of plasma cholesterol (5.1 mg/dl vs. 71.3 mg/dl, n=5) and triglycerides (17.6 mg/dl vs. 80.4 mg/dl, n=5) as compared to wild-type (WT) littermate controls. Despite modest increases in liver mass (1.14±0.03 g vs. 0.94±0.03 g, n=5) and liver lipid content (3.54±0.46% vs. 0.80±0.57% liver mass, n=4), Surf4 LKO mice show no signs of liver dysfunction or hepatosteatosis as evaluated by serum liver function markers and histology. Consistent with a role for SURF4 in PCSK9 secretion, plasma PCSK9 levels are reduced in Surf4 LKO mice (17.8±2.6 μg/ml vs. 46.0±7.7 μg/ml, n=6) while liver PCSK9 levels remain unchanged. Given that Pcsk9 -/- mice exhibit an approximately 50% reduction in plasma cholesterol, the magnitude of hypocholesterolemia in Surf4 LKO mice suggests that other cargoes involved in lipoprotein metabolism might also depend on SURF4 for secretion. Indeed, an unbiased secretomic study by mass spectrometry revealed that secretion of several lipoproteins, including APOA1, APOA2, and APOB, is reduced in SURF4 null Huh7 cells. As expected, Surf4 LKO mice show reduced APOB and lipoprotein secretion rate. In contrast to Huh7 cells, which demonstrate broad transcriptional changes in response to SURF4 deletion, the livers from Surf4 LKO mice exhibit few transcriptional changes, including the downregulation of genes involved in fatty acid synthesis. Conclusions: These results indicate that the cargo receptor SURF4 has pleiotropic functions in mammalian lipoprotein regulation and may represent a promising target for therapeutic development.

Hepato-toxicological and lipid profile of male Wistar rats following chronic carbamazepine, gabapentin, and carbamazepine-gabapentin adjunctive treatment

Aim: This study evaluated the hepatotoxicity and lipid profiles of male Wistar rats following chronic carbamazepine (CBZ), gabapentin (GBP) and carbamazepine-gabapentin (CBZ+GBP) adjunctive treatment.&#x0D; Methods: Twenty-eight male Wistar rats were randomized into 4 groups (n = 7) to receive daily oral administration of normal saline (0.2ml), or CBZ (25 mg/kg), or GBP (50 mg/kg), or the sub-therapeutic dose of CBZ (12.5 mg/kg) and GBP (25 mg/kg) combination for 56 days. Thereafter, blood and liver homogenate were subjected to biochemical analysis, while liver tissues were processed for the histomorphological investigation. Data were analysed statistically, while p&lt; 0.05 was taken as level of significance.&#x0D; Results: Activities of alanine phosphatase and aspartate aminotransferase significantly increased in the CBZ and CBZ + GBP treated rat. CBZ and CBZ + GBP treatments increased the plasma concentration of low-density lipoprotein and total cholesterol. The liver concentration of malondialdehyde increased significantly in all the treated groups relative to control. There were severe vascular congestions in theliver of the CBZ treated rats, this was moderate in the GBP and CBZ + GBP treated rats.&#x0D; Conclusion: Chronic use of CBZ may induce hepatotoxicity and lipid profile derangement, GBP and CBZ + GBP adjunctive treatment may be saver than treatment with CBZ.

Effects of dietary L-carnitine on puberty indices in the young breeder rooster

The aim of current study was to investigate the effect of dietary L-Carnitine (LC) in immature roosters on reproductive hormones, lipid profile and testicular histology at the time of maturity. Eighteen 12-wk-old breeder roosters (Ross 308) of similar weights were randomly allocated into 3 dietary treatments (LC-0: basic diet, LC-250: basic diet + 250 mg LC/kg of diet, LC-500: basic diet + 500 mg of LC/kg of diet) in 6 replicates. The feeding program and photoperiod regimen were performed based on ROSS 308 management handbook. Dietary LC supplementation markedly improved testicle weight and testicle index (p < 0.05). Comb height was also affected by LC supplementation (p < 0.05). The testicle weight and index, comb height, and shank lengths improved linearly with increasing levels of dietary LC (p < 0.05). The LC-250 and LC-500 diets significantly improved the number of sertoli cells (NSC), height epithelium seminiferous tubules (HEST), seminiferous tubules diameter (STD), spermiogenesis index (SI) and tubular differentiation index (TDI) of rooster's testis tissue (p < 0.05). The number of seminiferous tubules (NST) was affected by of the amount of LC (p < 0.05). The roosters on the LC-250 mg/kg diet had longer HEST compared to roosters that received the LC-500 mg/kg diet (p < 0.05). Testicular histology parameters increased in a linear and quadratic manner in response to increasing levels of LC (p < 0.05). Dietary LC significantly increased (p < 0.05) plasma concentrations of testosterone, GnRH, LH, FSH and High-Density Lipoprotein (HDL), but reduced the plasma concentration of Low-Density Lipoprotein (LDL). However, no significant differences were observed between LC-250 and LC-500 groups in these parameters. Plasma testosterone, GnRH, LH, LDL and HDL were affected in a linear and quadratic manner in response to increasing levels of LC (p < 0.05). Similarly, FSH increased linearly with increasing dietary LC (p < 0.05). Thus, adding up to 250 mg of LC per kg of diet of the rooster chicken can improve reproductive hormones, blood lipids and testicular histology parameters at the time of maturity.

Daily Consumption of a Specially Formulated Essential Amino Acid-Based Dietary Supplement Improves Physical Performance in Older Adults With Low Physical Functioning.

We have investigated the hypothesis that nutritional supplementation of the diet in low-physical-functioning older individuals with a specially formulated composition based on essential amino acids (EAAs) would improve physical function as compared to supplementation with the same amount of whey protein. A third group of comparable volunteers were given nutrition education but no supplementation of the diet. After 6 weeks of whey protein supplementation (n = 32), there was no effect on the distance walked in 6 minutes, but the distance walked improved significantly from the pre-value after 12 weeks of whey supplementation. EAA consumption (n = 28) significantly improved walking distance at both 6 and 12 weeks. The distance walked at 12 weeks (419.0 ± 25.0 m) was 35.4 m greater than the pre-value of 384.0 ± 23.0 m (p < .001). The increase in distance walked by the EAA group was also significantly greater than that in the whey group at both 6 and 12 weeks (p < .01). In contrast, a decrease in distance walked was observed in the control group (n = 32) (not statistically significant, NS). EAA supplementation also improved grip strength and leg strength, and decreased body weight and fat mass. Plasma low-density lipoprotein concentration was significantly reduced in the EAA group, as well as the concentration of macrophage migration inhibitory factor. There were no adverse responses in any groups, and compliance was greater than 95% in all individuals consuming supplements. We conclude that dietary supplementation with an EAA-based composition may be a beneficial therapy in older individuals with low physical functional capacity. Clinical Trials Registration Number: This study was registered with ClinicalTrials.gov: NCT03424265-"Nutritional interventions in heart failure."

Metabolomics Approach Explore Diagnostic Biomarkers and Metabolic Changes in Heat-Stressed Dairy Cows.

Simple SummaryHeat stress results in a decline in the production performance of the dairy cows. This study explored the metabolomes of milk and blood plasma in heat-stressed cows by means of 1H nuclear magnetic resonance (1H NMR)-based metabolomics tools. Findings of the current experiment reveal that HS alters the metabolic composition of milk and blood plasma in lactating dairy cows. In brief, HS alters twelve metabolites in blood plasma and eight metabolites in milk, which are primarily involved in proteolysis, gluconeogenesis, and milk fatty acid synthesis, suggesting that these metabolites could be possible biomarkers for heat-stressed dairy cows.In the present experiment, we investigated the impact of heat stress (HS) on physiological parameters, dry matter intake, milk production, the metabolome of milk, and blood plasma in lactating Holstein dairy cows. For this purpose, 20 Holstein lactating cows were distributed in two groups in such a way that each group had 10 cows. A group of 10 cows was reared in HS conditions, while the other group of 10 cows was reared in the thermoneutral zone. The results of the experiment showed that cows subjected to HS had higher respiration rates (p < 0.01) and greater rectal temperature (p < 0.01). Results of milk production and composition explored that HS lowered milk production (p < 0.01) and milk protein percentage (p < 0.05) than cows raised in a thermoneutral place. Furthermore, HS increased the concentrations of N-acetyl glycoprotein, scyllo-inositol, choline, and pyridoxamine in milk, while HS decreased the concentrations of O-acetyl glycoprotein, glycerophosphorylcholine, citrate, and methyl phosphate in milk. Moreover, HS enhanced plasma concentrations of alanine, glucose, glutamate, urea, 1-methylhistidine, histidine, and formate in cows, while the plasma concentration of low-density lipoprotein, very-low-density lipoprotein, leucine, lipid, and 3-hydroxybutyrate decreased due to HS. Based on the findings of the current research, it is concluded that HS alters the milk and blood plasma metabolites of lactating Holstein dairy cows. Overall, in the current experiment, HS altered eight metabolites in milk and twelve metabolites in the plasma of lactating Holstein dairy cows. Furthermore, the current study explored that these metabolites were mainly involved in proteolysis, gluconeogenesis, and milk fatty acid synthesis and could be potential biomarkers for dairy cows undergoing HS.

The association between maternal lipid profile after birth and offspring risk of autism spectrum disorder

PurposeMaternal obesity has been consistently associated with offspring risk for ASD, as well as lipid metabolism derangements. However, few ASD studies have examined maternal lipids in conjunction with maternal prepregnancy body mass index (BMI). MethodsThis nested case-control study was based on the Boston Birth Cohort, a prospective cohort study of mother-child dyads recruited at the Boston Medical Center. Maternal blood samples were collected shortly after delivery and analyzed for total plasma cholesterol, HDL, and triglyceride (TG) concentrations. Low-density lipoprotein (LDL) was subsequently calculated by the Friedewald equation. Cases were identified using ASD diagnoses in children’s medical records. The odds of ASD were estimated with continuous lipid levels for a linear relationship, and we further explored the nonlinear relationship using the tertile of each lipid analyte with the highest tertile as the reference group. Logistic regression was used to estimate the risk of ASD adjusting for potential confounders. The analyses were performed separately for mothers with normal weight and overweight/obese based on maternal prepregnancy BMI. ResultsOne standard deviation decrease in postpartum maternal LDL was associated with increased odds of ASD aOR 1.35 [1.04–1.75]. There was no association between postpartum maternal HDL and TG levels and ASD risk. Decreasing levels of LDL were not associated with ASD risk in normal-weight mothers (aOR 1.2 [0.83–1.75]), but the ASD risk was more pronounced in overweight and obese mothers (aOR 1.54 [1.03–2.27]). Follow-up analysis of nonlinear association models showed that, when compared to the highest tertile, lower maternal LDL concentrations were associated with approximately two times increased risk of ASD (first tertile: aOR 2.49 [1.27–4.87] and second tertile: aOR 2.79 [1.42–5.48]). A similar pattern was observed with overweight/obese mothers but not in normal-weight mothers. ConclusionsLower maternal postpartum plasma LDL concentration was associated with increased odds of ASD in offspring among children born to overweight and obese mothers. Our findings suggest that both maternal BMI and lipids should be considered in assessing their role in offspring ASD risk, and additional longitudinal studies are needed to better understand maternal lipid dynamics during pregnancy among normal-weight and overweight/obese mothers.

Long-term high-fat diet disrupts lipid metabolism and causes inflammation in adult male rats: possible intervention of endoplasmic reticulum stress

This study investigated the effect of long-term high-fat diet (HFD) on plasma lipid profile and probability of inflammation in adult rats. After weaning, male offspring were divided into six groups based on diet type and medication. After 20 weeks of dietary intake, 4-PBA (endoplasmic reticulum (ER) stress inhibitor) was injected for three days. Then, blood samples were taken to measure plasma concentrations of low-density lipoprotein (LDL), triglyceride (TG), high-density lipoprotein (HDL), cholesterol, leptin and interleukin 1-β (IL 1-β). The HFD increased body weight and food intake and intra-abdominal fat and thymus weights, which were associated with elevated plasma leptin level. Moreover, HFD increased plasma concentrations of TG, LDL, cholesterol and IL 1-β and decreased HDL level. Injection of 4-PBA reversed the plasma parameters changes caused by HFD. It seems that long-term HFD feeding through inducing the ER stress, disrupted the lipid metabolism and resulted in inflammation.

Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture.

Background: Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall.Methods: Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture.Results: Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P < 0.05). Multivariate analysis revealed that only average LDL infiltration remained as a significant variable (P < 0.05). The prediction model derived showed good performance for rupture prediction (AUC, 0.885; 95% CI, 0.794–0.976).Conclusions: Ruptured aneurysms showed significantly higher LDL infiltration compared to unruptured ones. Our results suggested that lipid infiltration may promote aneurysm rupture. Lipid infiltration characteristics should be considered when assessing aneurysm rupture risk.

Trilactic glyceride regulates lipid metabolism and improves gut function in piglets.

Glycerol-lactate esters are energy supplements for exercise, but effects of trilactic glyceride (TLG) on intestinal function and hepatic metabolism are unknown. We found that dietary supplementation with 0.5% TLG to weanling piglets decreased plasma concentrations of low-density lipoprotein and gamma-glutamyl transferase but increased those of D-xylose and high-density lipoprotein. TLG supplementation enhanced mRNA levels for fatty acid synthase (FASN) and SLC27A2 in white adipose tissue; insulin receptor in duodenum; aquaporin-8 in ileum, jejunum and colon; aquaporin-10 in duodenum and ileum; nuclear factor like-2 in jejunum and colon; glutathione S-transferase and phosphoenolpyruvate carboxykinase-1 in intestines; and abundances of claudin-1 and occludin proteins. TLG supplementation decreased mRNA levels for: hepatic hormone-sensitive lipase E, lipoprotein lipase, FASN, insulin-like growth factor-binding protein-3, and SLC27A2; and intestinal lipoprotein lipase, FASN and NADPH oxidase. Furthermore, TLG supplementation enhanced abundances of genus Bifidobacterium, while reducing abundances of family Enterobacteriaceae in ileum, colon and cecum; jejunal caspase-3 protein and diarrhea rate. In conclusion, dietary supplementation with TLG modulated lipid metabolism and alleviated diarrhea by improving intestinal function and regulating intestinal microflora in piglets.

Reclamation of Astragalus By-Product through Dietary Inclusion in Ruminant Diets: Effects on Growth Performance, Nutrient Digestibility, Rumen Fermentation, Blood Biochemical Parameters, and Humoral Immune Response in Sheep.

This study was conducted to investigate the effects of Astragalus by-product (ABP) through dietary supplementation at different levels on performance, nutrient digestibility, rumen fermentation, blood metabolites, and immune response in sheep. Twenty-four Doper × Small Tail Han ewes (6-7 months of age; 29.07 ± 2.28 kg initial body weight) were randomly assigned to one of three treatments for a 47 d feeding period. Treatments consisted of the sheep diet supplemented with 0% ABP-control, 10% ABP, or 15% ABP of the diet (dry matter basis). Blood samples were collected on days 0, 15, 30, and 45 of the feeding period. APB supplementation did not affect growth performance and apparent digestibility of organic matter, crude protein, and acid detergent fibre (P > 0.05). However, ether extract digestibility was decreased in the 10% ABP group and increased in the 15% ABP group (P < 0.001), and both 10% ABP and 15% ABP decreased the neutral detergent fibre digestibility (P=0.005). Feeding ABP increased rumen pH (P < 0.001) and ammonia N (P < 0.001) and decreased concentrations of acetate (P=0.007) and propionate (P=0.001) which resultantly increased the acetate-to-propionate ratio (P < 0.001) in ruminal fluid. There were no interaction effects between treatment and sampling time for plasma metabolites and immunity (P > 0.05). However, inclusion of dietary 10% ABP decreased concentrations of plasma cholesterol (P=0.043). Also, plasma concentrations of low-density lipoprotein decreased on days 30 and 45 (P=0.017) of the feeding period. Metabolite concentrations of total protein, albumin, globulin, blood urea N, glucose, triglyceride, and high-density lipoprotein cholesterol and humoral immune indicators were not affected (P > 0.05) by dietary ABP supplementation. The results suggest that ABP could be reclaimed through dietary inclusion in animal feed since it had beneficial effects on rumen fermentation patterns and lipid metabolism and had no adverse effects on performance and humoral immunity in sheep.

Glucagon Receptor Signaling and Lipid Metabolism.

Glucagon is secreted from the pancreatic alpha cells upon hypoglycemia and stimulates hepatic glucose production. Type 2 diabetes is associated with dysregulated glucagon secretion, and increased glucagon concentrations contribute to the diabetic hyperglycemia. Antagonists of the glucagon receptor have been considered as glucose-lowering therapy in type 2 diabetes patients, but their clinical applicability has been questioned because of reports of therapy-induced increments in liver fat content and increased plasma concentrations of low-density lipoprotein. Conversely, in animal models, increased glucagon receptor signaling has been linked to improved lipid metabolism. Glucagon acts primarily on the liver and by regulating hepatic lipid metabolism glucagon may reduce hepatic lipid accumulation and decrease hepatic lipid secretion. Regarding whole-body lipid metabolism, it is controversial to what extent glucagon influences lipolysis in adipose tissue, particularly in humans. Glucagon receptor agonists combined with glucagon-like peptide 1 receptor agonists (dual agonists) improve dyslipidemia and reduce hepatic steatosis. Collectively, emerging data support an essential role of glucagon for lipid metabolism.

Effect of feed supplementation with Satureja khuzistanica essential oil on performance and physiological parameters of broilers fed on wheat- or maize-based diets

ABSTRACT1. The aim of this study was to evaluate various levels of Satureja khuzistanica essential oil (SKEO) on performance and physiological parameters of broilers fed on wheat- or maize-based diets.2. Treatments consisted of two cereals (maize- or wheat-based diets) and three levels of SKEO)0, 250 and 500 mg/kg).3. Feed intake (FI) and body weight gain (BWG) decreased in broilers fed on the wheat-based diets compared to the control diet. Dietary supplementation of 500 mg/kg SKEO increased FI and BWG. Dietary SKEO supplementation was effective in improving FI and BWG only in wheat-based diets and was effective in improving feed conversion ratio (FCR) in both diets.4. Dietary supplementation of 500 mg/kg SKEO caused a significant decrease in plasma cholesterol and triglycerides. Also, plasma low-density lipoprotein concentration was decreased in broilers fed on 250 and 500 mg/kg of SKEO. Plasma cholesterol levels in birds fed on the wheat-based diets were lower than in those fed on maize-based diets.5. Dietary supplementation of 500 mg/kg SKEO increased caecal population of Lactobacillus and reduced total bacterial and Escherichia coli count. Caecal population of Lactobacillus decreased in broilers fed on the wheat-based diets.6. Digesta viscosity was increased in broilers fed on the wheat-based diets and decreased in broilers fed on 500 mg/kg SKEO compared to the control diet. Dietary SKEO supplementation was effective in reducing digesta viscosity values only in wheat-based diets.7. Villus height of the duodenum and jejunum decreased in broilers fed on the wheat-based diets. Dietary supplementation of 500 mg/kg SKEO increased villus height and villus height-to-crypt depth ratios and decreased crypt depth of the duodenum compared to the control diet.8. It can be concluded that dietary SKEO supplementation was effective in improving FI, BWG and FCR values in wheat-based diets.

Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism

Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low density lipoprotein (LDL) receptor (LDLR) degradation, this study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression. Herein, we demonstrate the existence of two independent effects of ER stress on PCSK9 expression and secretion. In cultured HuH7 and HepG2 cells, agents or conditions that cause ER Ca2+ depletion, including thapsigargin, induced SREBP2-dependent up-regulation of PCSK9 expression. In contrast, a significant reduction in the secreted form of PCSK9 protein was observed in the media from both thapsigargin- and tunicamycin (TM)-treated HuH7 cells, mouse primary hepatocytes, and in the plasma of TM-treated C57BL/6 mice. Furthermore, TM significantly increased hepatic LDLR expression and reduced plasma LDL concentrations in mice. Based on these findings, we propose a model in which ER Ca2+ depletion promotes the activation of SREBP2 and subsequent transcription of PCSK9. However, conditions that cause ER stress regardless of their ability to dysregulate ER Ca2+ inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake. Taken together, our studies provide evidence that the retention of PCSK9 in the ER may serve as a potential strategy for lowering LDL cholesterol levels.

EFFECT OF FLAXSEED OIL SUPPLEMENTION DURING PRE AND POSTPARTUM ON SOME PHYSIOLOGICAL PARAMETERS AND PRODUCTIVE PERFORMANCE OF FRIESIAN COWS

The objective of this study was to evaluate the effects of flaxseed oil supplementation into the ration of Friesian cows on their productive, somatic cell count (SCC), physiological and blood parameters during summer season. Twenty four dry pregnant Friesian cows averaged 607±22.5 kg live body weight (LBW) at 2-3 parities were randomly assigned into two groups (12 cows in each group). Cows in group 1st (G1) did not treatment and served as a control, while those in the 2nd were c received 2% of DM intake flaxseed oil from 45 days pre-partum until 120 days post-partum. Results revealed that body temperatures degrees of rectal (RT), skin at white (STW) and black (STB) as well as respiration rate (RR) during heat stress period in summer months (June, July, August and September) significantly (P<0.05) decreased with flaxseed oil as compared to the control group. Flaxseed oil diet improved (P<0.05) digestibility and rumen activity. Average daily dry matter intake (DMI) and DCP pre-partum were nearly similar for control and flaxseed oil treatment, while the intake of TDN increased significantly (P<0.05) with flaxseed oil supplementation compared to the control group. Cows of tested treatment On post partum state, DMI and TDN intake were significant higher with oil supplemental ration than the control group, but the difference did not significant between treatments respecting DCPI in this phase. Cows of treatments were higher in red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin (Hb) concentration and haematocrit percentage (HCT, %) than those of the control group. Cows treatment were higher significantly lymphocytes and significantly lower moncytes than control group. All protein fraction concentrations were higher in treated than in control group (G1). Concentrations of high density lipoprotein and triglyceride were higher significantly (P<0.05) in G2 than the control group (G1), but, plasma low density lipoprotein concentrations were lower significantly (P<0.05) in G2 than the control group (G1). Daily milk yield and 4% fat corrected milk were higher significantly by 19.37 and 29.99%, respectively compared with control. The G2 had higher (P<0.05) percentages of fat, lactose and total solids as compared to G1, while protein and solids not fat percentages were similar to G1. Diet supplemented with flaxseed oil showed lower (P<0.05) somatic cell count in milk as compared to G1. Feed conversion improved (P<0.05) in G2 than in G1. Economic efficiency was higher with flaxseed oil- ration than that of control one free from oil. It could be concluded that flaxseed oil supplementation in diet of Friesian cows (2% /kg DMI) during pre- and post-partum period heat stress could be eliminated and improved digestibility, productive performance and economic efficiencies as well as immune-response of Friesian cows without adversity effects on haematological and biochemical parameters.