Lipoprotein Cholesterol Concentrations Research Articles

Effects of dietary metabolizable energy level on hepatic lipid metabolism and cecal microbiota in aged laying hens

Lipid metabolic capacity, feed utilization, and the diversity of gut microbiota are reduced in the late laying stage for laying hens. This experiment aimed to investigate the effects of different levels of dietary metabolizable energy (ME) on hepatic lipid metabolism and cecal microbiota in late laying hens. The 216 Peking Pink laying hens (57-wk-old) were randomly assigned to experimental diets of 11.56 (HM = high ME), 11.14 (MM = medium ME), or 10.72 (LM = low ME) MJ of ME/kg, with each dietary treatment containing 6 replicates per group and 12 chickens per replicate. The HM group showed higher triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) concentrations in the liver compared with the LM group; second, the HM group showed higher TG concentration and the LM group showed lower T-CHO concentration compared with MM group; finally, the HM group showed a lower hepatic lipase (HL) activity compared with the MM and LM groups (P < 0.05). There was a significant difference in the microbial community structure of the cecum between the HM and MM groups (P < 0.05). The decrease of dietary ME level resulted in a gradual decrease relative abundance of Proteobacteria. At the genus level, beneficial bacteria were significantly enriched in the LM group compared to the MM group, including Faecalibacterium, Lactobacillus, and Bifidobacterium, (linear discriminant analysis [LDA] >2, P <0.05). In addition, at the species level, Lactobacillus crispatus, Parabacteroides gordonii, Blautia caecimuris, and Lactobacillus johnsonii were significantly enriched in the LM group (LDA>2, P < 0.05). The HM group had a higher abundance of Sutterella spp. compared to the LM group (LDA>2, P <0.05). In conclusion, this research suggests that the reduction in dietary energy level did not adversely affect glycolipid metabolism or low dietary ME (10.72 MJ/kg). The findings can be helpful for maintaining intestinal homeostasis and increasing benefit for gut microbiota in late laying hens.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96–1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. Of the participants who reached the age of 70years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Relationship between remnant cholesterol and risk of kidney stones in U.S. Adults: a 2007–2016 NHANES analysis

Purpose Remnant cholesterol (RC) is the cholesterol content of triglyceride-rich lipoproteins. This study aimed to investigate the association between RC levels and kidney stones in U.S. adults. Methods Data were obtained from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES). A total of 10,551 participants with complete data were included and analyzed in this study. Univariate and multivariate logistic regression analysis, restricted cubic spline function, subgroup analysis and mediation analysis were preformed to estimate the independent relationship between RC levels and kidney stones. Results Participants with stone formation had higher levels of RC than those with without stone formation (25.78 ± 13.83 vs 23.27 ± 13.04, p< 0.001). The results of logistic regression analysis and dose-response risk curves revealed a positive nonlinear association between RC levels and risk of kidney stones [univariate: adjusted odds ratio (aOR) =2.388, 95% CI: 1.797–3.173, p< 0.001; multivariate: aOR = 1.424, 95% CI: 1.050–1.929, p = 0.023]. Compared with the discordantly low RC group, the discordantly high RC group was associated with increased risk of kidney stones (aOR = 1.185, 95% CI: 1.013–1.386, p= 0.034). Similar results were demonstrated according to the discordance of different clinical cut points. And metabolic syndrome parameters and vitamin D levels parallelly mediated the association between RC and kidney stone risk. Conclusions Higher RC levels were independently associated with an increased risk of kidney stone incidence.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial.

Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 .

Guiding Dyslipidemia Treatment: A Population Pharmacokinetic-Pharmacodynamic Framework for Obicetrapib.

Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3-compartment model with 4-compartment transit absorption and first-order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) concentrations. The maximum stimulatory effect of obicetrapib on LDL-C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL-C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL-C and HDL-C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision-making throughout the development lifecycle.

GROWTH PERFORMANCE AND LIPID PROFILE OF ARCHACHATINA MARGINATA (GIANT AFRICAN LAND SNAIL) FED VARYING LEVELS OF RIPE EGGPLANT FRUITS BASED DIETS

The performance of African giant land snails (Archachatina marginata) fed ripe eggplant fruits was studied using eighty-four (84) juvenile (four months old) Archachatina marginata for eight (8) weeks. The study evaluated the snails' growth performance and lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides). The snails were divided into four treatment groups, with twenty-one (21) snails per group in a completely randomized design (CRD). Treatments 1, 2, 3 and 4 had varying levels of ripe eggplant fruits at 0%, 5%, 10% and 15% inclusion levels respectively. Isocaloric and isonitrogenous feeds and water were provided ad libitum, while other management practices were strictly adhered to. The results showed no significant differences (P&gt;0.05) in growth performance across treatments. The results also revealed that total cholesterol decreased (P&lt;0.05) significantly as the levels of ripe eggplant fruits increased across treatments. There were no significant differences (P&gt;0.05) in low-density lipoprotein and triglycerides, while high-density lipoprotein differed (P&lt;0.05) significantly across treatments. The result also showed a linear increase in high-density lipoprotein ("good" cholesterol) as the levels of ripe eggplant fruits increased across treatments. Therefore, a 15% inclusion level of ripe eggplant fruits in the diet of Archachatina marginata reduces total cholesterol levels and increases high-density lipoprotein without any adverse effect on growth. The study recommends using ripe eggplant fruits to formulate diets for animals with high cholesterol content and high levels of low-density lipoprotein in their meat.

Effect of &lt;i&gt;Vernonia amygdalina&lt;/i&gt; and fish oil-supplemented biscuits on lipid profile parameters and blood glucose concentration of diabetic rats

Biscuit, a popular snack, serve as an ideal vehicle for incorporating therapeutic agents for disease management. This study aimed to assess the effect of Vernonia amygdalina (VO) and fish oil (FO)-supplemented biscuits (VFSB) on the total lipid profile and blood glucose concentration of diabetic rats. Forty-nine Wistar rats were allocated into seven groups (A to G). Upon induction and confirmation of diabetes in experimental rats, fasting blood glucose (FBG) level were monitored weekly using glucometer. Twenty-four hours after the last day of treatment, rats were sacrificed and serum total cholesterol (TC), triglyceride (TG), High-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were assayed using assay kits. Results showed a significant (p &lt; 0.05) reduction in FBG, TC, LDL-c, and TG concentrations in biscuit fed groups D, E, and F compared to group B fed VFSB. High-density lipoprotein cholesterol levels significantly increased (p &lt; 0.05) in groups D, E, and F compared to Group B. In conclusion, Vernonia amygdalina and fish oil-supplemented biscuits exhibited a glucose-lowering effect and mitigated dyslipidemia associated with diabetes mellitus.

Effects of Corbicula fluminea meal in high-fat diet on growth, lipid metabolism and intestinal microbiota of juvenile rice field eel Monopterus albus

Corbicula fluminea meal was added to a high-fat diet for eight weeks to determine its effects on growth, lipid metabolism, and intestinal microbiota in juvenile rice field eel (Monopterus albus). C. fluminea meal was made of dried and crushed soft parts of freshwater clam. The study included four diets: a normal fat diet (6.63% lipid, CON), a high fat diet (12.61% lipid, HFD), and a high fat diet supplemented with 1% or 2% C. fluminea meal (CFM1 and CFM2, respectively). The results showed that: (1) the growth performance was higher in the HFD, CFM1 and CFM2 group compared with the CON group, the hepatosomatic index (HSI) was significantly higher in fish fed the high-fat diet than in those fed other diets. (2) Compared with the CON group, The levels of serum triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) contents, glutamate pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and the number of hepatic lipid droplets were significantly increased in the HFD group. The addition of C. fluminea meal both reduced liver damage and fat deposition. (3) The mRNA expressions of pparγ, fas, acc, me1, srebp1, g6pdh, hsl, lpl, cpt1, and cpt2 in the HFD group were significantly upregulated, while HFD supplemented with C. fluminea meal significantly downregulated the mRNA expressions of pparγ, fas, acc, me1, srebp1 and g6pdh and significantly upregulated the mRNA expressions of hsl and lpl. (4) The alpha diversity of intestinal microbial community in the HFD group was higher than those in the CON and CFM1 groups. The beta diversity revealed the microbial composition differed in the HFD group from the CON and CFM1 groups. The abundance of Firmicutes in the HFD group increased significantly compared with the CON and CFM1 groups, while the abundances of Cetobacterium decreased. In conclusion, the high-fat diet resulted in abnormal liver fat deposits and intestinal microbiota dysfunction in M. albus, but HFD supplemented with 1% or 2% C. fluminea meal reduced these negative effects.

Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition

BackgroundIt is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. ObjectivesThis study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. MethodsSix-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. ResultsAlthough the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. ConclusionsIt is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.

Validation of Nutritional Approaches to Modulate Cardiovascular and Diabetic Risk Factors in Patients with Hypertriglyceridemia or Prediabetes-The MoKaRi II Randomized Controlled Study.

Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of both clinical pictures. For the 10-week randomized, controlled, intervention study, 67 subjects with elevated plasma triglyceride (TG) concentrations (≥1.7 mmol/L) and 69 subjects with elevated fasting glucose concentrations (≥5.6 < 7.0 mmol/L) were recruited. The intervention groups received specially developed, individualized menu plans and regular counseling sessions to lower (A) TG or (B) fasting glucose and glycated hemoglobin A1c as well as other cardiovascular and diabetic risk factors. The hypertriglyceridemia intervention group was further supplemented with fish oil (3.5 g/d eicosapentaenoic acid + docosahexaenoic acid). The two control groups maintained a typical Western diet. Blood samples were taken every 2 weeks, and anthropometric data were collected. A follow-up examination was conducted after another 10 weeks. In both intervention groups, there were comparable significant reductions in blood lipids, glucose metabolism, and anthropometric parameters. These results were, with a few exceptions, significantly more pronounced in the intervention groups than in the corresponding control groups (comparison of percentage change from baseline). In particular, body weight was reduced by 7.4% (6.4 kg) and 7.5% (5.9 kg), low-density lipoprotein cholesterol concentrations by 19.8% (0.8 mmol/L) and 13.0% (0.5 mmol/L), TG concentrations by 18.2% (0.3 mmol/L) and 13.0% (0.2 mmol/L), and homeostatic model assessment for insulin resistance by 31.8% (1.1) and 26.4% (0.9) (p < 0.05) in the hypertriglyceridemia and prediabetes intervention groups, respectively. Some of these changes were maintained until follow-up. In patients with elevated TG or fasting glucose, implementing individualized menu plans in combination with regular counseling sessions over 10 weeks led to a significant improvement in cardiovascular and diabetic risk factors.

Dietary Lysophosphatidylcholine Improves the Uptake of Astaxanthin and Modulates Cholesterol Transport in Pacific White Shrimp Litopenaeus vannamei.

Astaxanthin (AST), functioning as an efficient antioxidant and pigment, is one of the most expensive additives in shrimp feeds. How to improve the uptake efficiency of dietary astaxanthin into farmed shrimp is of significance. The present study investigated the effects of lysophosphatidylcholine (LPC), an emulsifier, on dietary astaxanthin efficiency, growth performance, body color, body composition, as well as lipid metabolism of juvenile Pacific white shrimp (average initial body weight: 2.4 g). Three diets were prepared: control group, the AST group (supplemented with 0.02% AST), and the AST + LPC group (supplemented with 0.02% AST and 0.1% LPC). Each diet was fed to triplicate tanks, and each tank was stocked with 30 shrimp. The shrimp were fed four times daily for eight weeks. The AST supplementation improved the growth of white shrimp, while LPC further promoted the final weight of shrimp, but the whole-shrimp proximate composition and fatty acid composition were only slightly affected by AST and LPC. The LPC supplementation significantly increased the astaxanthin deposition in the muscle. The LPC supplementation significantly increased the shell yellowness of both raw and cooked shrimp compared to the AST group. Moreover, the dietary LPC increased the high-density lipoprotein-cholesterol content but decreased the low-density lipoprotein-cholesterol content in the serum, indicating the possible regulation of lipid and cholesterol transport. The addition of astaxanthin significantly up-regulated the expression of npc2 in the hepatopancreas compared to the control group, while the addition of LPC down-regulated the expression of mttp compared to the AST group. In conclusion, the LPC supplementation could facilitate the deposition of dietary astaxanthin into farmed shrimp and further enlarge the beneficial effects of dietary astaxanthin. LPC may also independently regulate shrimp body color and cholesterol transportation. This was the first investigation of the promoting effects of LPC on dietary astaxanthin efficiency.

Effects of Phytosterol Ester Supplementation on Egg Characteristics, Eggshell Ultrastructure, Antioxidant Capacity, Liver Function and Hepatic Metabolites of Laying Hens during Peak Laying Period.

The aim of this experiment was to investigate the effects of dietary Phytosterol Ester (PSE) supplementation on egg characteristics, eggshell ultrastructure, antioxidant capacity, liver function, hepatic metabolites, and its mechanism of action in Hy-Line Brown laying hens during peak laying period. A total of 256 healthy Hy-Line Brown laying hens were randomly allocated into four groups. The hens in the control group were fed a basal diet, while those in the experimental groups were fed a basal diet further supplemented with 10, 20, and 40 mg/kg PSE, respectively. It was found that the addition of 20 mg/kg and 40 mg/kg PSE to the diets increased egg weight, but decreased egg breaking strength (p < 0.05). The addition of PSEs to the diets increased albumen height and Haugh unit in all experimental groups (p < 0.05). Electron microscopic observation revealed that the mammillary thickness increased significantly at doses of 20 and 40 mg/kg, but the total thickness decreased, and the effective thickness also thinned (p < 0.05). The mammillary width narrowed in all experimental groups (p < 0.001). Dietary supplementation with 40 mg/kg PSE significantly increased egg yolk Phenylalanine, Leucine, and Isoleucine levels (p < 0.05). In untargeted liver metabolomic analyses, L-Phenylalanine increased significantly in all experimental groups. Leucyl-Lysine, Glutamyl-Leucyl-Arginine, and L-Tryptophan increased significantly at doses of 10 and 20 mg/kg (p < 0.05), and L-Tyrosine increased significantly at doses of 10 and 40 mg/kg (p = 0.033). Aspartyl-Isoleucine also increased significantly at a dose of 10 mg/kg (p = 0.044). The concentration of total protein in the liver was significantly higher at doses of 20 and 40 mg/kg than that of the control group, and the concentrations of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (p < 0.05). The concentration of triglyceride and alkaline phosphatase were significantly reduced in all experimental groups (p < 0.05). Steatosis and hemorrhage in the liver were also improved by observing the H&E-stained sections of the liver. Concerning the antioxidant capacity in the liver, malondialdehyde concentration was significantly reduced (p < 0.05) at a dose of 40 mg/kg. In the ovary, malondialdehyde and nitric oxide concentrations were significantly reduced (p < 0.001). In all the experimental groups, plasma nitric oxide concentration was significantly decreased while superoxide dismutase was significantly increased, and total antioxidant capacity concentration was significantly increased (p < 0.05) in the 10 mg/kg and 40 mg/kg doses. Metabolomics analyses revealed that PSEs play a role in promoting protein synthesis by promoting Aminoacyl-tRNA biosynthesis and amino acid metabolism, among other pathways. This study showed that the dietary addition of PSEs improved egg characteristics, antioxidant capacity, liver function, and symptoms of fatty liver hemorrhagic syndrome in Hy-Line Brown laying hens at peak laying stage. The changes in liver metabolism suggest that the mechanism of action may be related to pathways such as Aminoacyl-tRNA biosynthesis and amino acid metabolism. In conclusion, the present study demonstrated that PSEs are safe and effective dietary additives as an alternative to antibiotics.

Metabolic effects of testosterone added to intensive lifestyle intervention in older men with obesity and hypogonadism.

Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. Secondary analysis of a randomized, double-blind, placebo-controlled trial. Veterans Affairs Medical Center. 83 older (age ≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and persistently low AM testosterone (< 10.4 nmol/L) associated with frailty. LT (weight management and exercise training) plus either testosterone (LT+TRT) or placebo (LT+Pbo) for six months. Primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure, and metabolic syndrome score. HbA1c decreased similarly in LT+TRT and LT+Pbo groups (-0.5% vs. -0.6%, respectively; p= 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in LT+Pbo group vs. 0.2 ± 1.1 mg/dL in LT+TRT group, p= 0.01) and adiponectin levels (-408 ± 489 ng/mL in TRT+LT group vs 1832 ± 468 ng/mL in LT+Pbo group, p= 0.02). In older men with obesity and hypogonadism, adding TRT for six months to LT does not result in further improved cardiometabolic profiles, and could potentially blunt some of the metabolic benefits induced by LT.

A new equation for estimating low-density lipoprotein cholesterol concentration based on machine learning.

Low-density lipoprotein cholesterol (LDL-C) is a crucial marker of cardiovascular system damage. In the Chinese population, the estimation of LDL-C concentration by Friedewald, Martin-Hopkins or Sampson equations is not accurate. The aim of this study was to develop a group of new equations for calculating LDL-C concentration using machine learning techniques and to evaluate their efficacy. A total of 182,901 patient samples were collected with standard lipid panel measurements. These samples were collated and randomly divided into a training set and a test set. In the training set, a new equation was constructed using polynomial ridge-regression and compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations in the test set. Subsequently, an additional set of 17,285 patient samples were collected to evaluate the performance of the new equation in clinical practice. The new equation, a ternary cubic equation, was accurate and easy to use, with a goodness-of-fit R2 of 0.9815 and an uncertainty MSE of 37.4250 on the testing set. The difference between the calculated value by the new equation and the measured value of LDL-C was small (0.0424 ± 5.1161 vs Friedewald equation: -13.3647 ± 17.9198, vs Martin/Hopkins and extended Martin/Hopkins equation: -6.4737 ± 8.1036, vs Sampson equation: -8.9252 ± 12.6522, P < .001). It could accurately calculate LDL-C concentration even at high triglyceride and low LDL-C. Furthermore, the new equation could also precisely calculate LDL-C concentration in actual clinical use (R2 = 0.9780, MSE = 24.8482). The new equation developed in this study can accurately calculate LDL-C concentration within the full concentration range of triglyceride and LDL-C, and can serve as a supplement to the direct determination of LDL-C concentration for the prevention, treatment, evaluation, and monitoring of atherosclerotic diseases, compared to the Friedewald, Martin/Hopkins and extended Martin/Hopkins, or Sampson equations.

A randomised double-blind placebo-controlled trial of a probiotic combination for manipulating the gut microbiota and managing metabolic syndrome

An increasing number of studies indicate that the occurrence of metabolic syndrome is significantly influenced by the host's gut microbiota and its metabolites. This study evaluated the potential application of a combination of Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631 for the clinical remission of metabolic syndrome. This research comprised 40 individuals with metabolic syndrome, 21 of whom were in the probiotic intervention group and 19 in the placebo control group. The intervention duration was 11 weeks and involved the daily intake of 1 × 1010 CFU of a probiotic combination comprising Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631. The serum biochemical indexes of the participants before and after the intervention were measured. After the intervention, faecal samples were collected to comprehensively analyse the gut microbiota of the participants by high-throughput sequencing and the faecal concentrations of target short-chain fatty acids by gas chromatography–mass spectrometry. The results showed that the 11-week probiotic intervention significantly reduced fasting blood glucose, fasting insulin, triglyceride, and low-density lipoprotein cholesterol concentrations in patients with metabolic syndrome and significantly increased the abundance of Bacteroidetes and some genera that produce short-chain fatty acids by regulating the abundance of gut microbial taxa that are strongly correlated with the clinical indicators of metabolic syndrome. These results demonstrated the beneficial effects of the probiotic combination on the clinical remission of metabolic syndrome, suggesting its potential application as an adjuvant strategy for the clinical treatment of metabolic syndrome in the future and laying a foundation for the further study of the mechanism of action of probiotics in alleviating metabolic syndrome.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Associations of ECG Signs of Ischemic and Non-Specific Signs of Metabolic Changes in the Myocardium With Unfavorable Cardiovascular Prognosis in a 7-Year Prospective Follow-Up of Young People Under 45 Years.

To study ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium and to determine their relationship with unfavorable cardiovascular prognosis in a 7-year prospective observation of young people under 45 years of age. A cross-sectional population survey of a random sample aged 25-44 years (n=1363) was conducted in Novosibirsk. The survey program used the standardized epidemiological Rose questionnaire. Biochemical tests were used to measure blood concentrations of total cholesterol (C), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and fasting blood plasma glucose. Systolic and diastolic BP (SBP, DBP), the presence of arterial hypertension (AH), body mass index (BMI), waist circumference (WC), and smoking status were assessed. ECG was recorded at rest in 12 standard leads followed by interpretation according to the Minnesota Code. The presence of ischemic and/or nonspecific ECG signs of metabolic changes in the myocardium was determined. Subjects with ECG signs of ischemic changes in the myocardium were selected for long-term follow-up and additional examination by cardiologists. Then the whole cohort was monitored for 7 years, and cardiovascular events were recorded, including using data from the WHO Myocardial Infarction Registry in Novosibirsk. For statistical analysis of the results, cardiovascular events were combined into a composite endpoint. During 7 years, 40 people (27 men and 13 women) had an unfavorable cardiovascular prognosis. Multivariate regression analysis showed that a 7-year unfavorable cardiovascular prognosis in people younger than 45 years was associated with signs of ischemic myocardial alterations identified on the background ECG (OR 5.319, 95% CI: 1.543-18.342, p=0.008) and nonspecific ECG signs of metabolic changes in the myocardium (OR 2.978, 95% CI: 1.216-7.216, p=0.017) regardless of age, gender, the presence of arterial hypertension (AH) and type 2 diabetes mellitus (DM2). In young people under 45 years of age, not only ECG signs of ischemic changes in the myocardium, but also nonspecific ECG signs of metabolic changes in the myocardium are associated with an unfavorable cardiovascular prognosis, directly and independently on age and gender, in a long-term, 7-year period.