T329S Mutation in the FMO3 Gene Alleviates Lipid Metabolic Diseases in Chickens in the Late Laying Period

The T329S mutation in flavin-containing monooxygenase 3 (FMO3) impairs the trimethylamine (TMA) metabolism in laying hens. The TMA metabolic pathway is closely linked to lipid metabolic diseases, such as atherosclerosis and fatty liver disease. We aimed to evaluate the effects of the T329S mutation in FMO3 on lipid metabolism in chickens during the late laying period. We selected 18 FMO3 genotyped individuals (consisting of six AA, six AT, and six TT hens) with similar body weight and production performance. The lipid metabolism and deposition characteristics of the laying hens with different genotypes were compared. The T329S mutation moderated the serum-lipid parameters in TT hens compared to those in AA and AT hens from 49 to 62 weeks. Furthermore, it reduced the serum trimethylamine N-oxide concentrations and increased the serum total bile acid (p < 0.05) and related lipid transporter levels in TT hens. Moreover, it significantly (p < 0.01) decreased atherosclerotic lesions and hepatic steatosis in TT hens compared to those in the AA and AT hens. Our findings may help improve the health status in laying hens during the late laying period.

Association between Non-HDL-C/HDL-C Ratio and Carotid Intima–Media Thickness in Post-Menopausal Women

Atherogenic lipoproteins (particularly, very low-density lipoproteins, VLDL) are associated with subclinical atherosclerosis. The present study aims at evaluating whether routinely analysed lipid parameters are associated with carotid intima–media thickness, a proxy for subclinical atherosclerosis. Lipid parameters from 220 post-menopausal women undergoing ultrasound investigation of the carotid arteries were analysed. Forty-five percent of women showed subclinical atherosclerosis on carotid ultrasound. The mean carotid intima–media thickness was 1.26 ± 0.38 mm. The mean value of the non-HDL-C/HDL-C ratio was 3.1 ± 1.2. Univariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima–media thickness (r = 0.21, p = 0.001). After adjusting for cardiovascular risk factors (age, systolic blood pressure, smoking, body mass index Homeostasis model assessment: insulin resistance and high-sensitivity C-Reactive-Protein), multivariate analysis showed a significant association between non-HDL-C/HDL-C ratio and intima–media thickness (β = 0.039, p = 0.04). Logistic regression analysis showed that the highest tertile of the non-HDL-C/HDL-C ratio was associated with the presence of carotid plaques (OR = 3.47, p = 0.003). Finally, a strong correlation between non-HDL-C/HDL-C ratio and cholesterol bound to VLDL (r = 0.77, p < 0.001) has been found. Non-HDL-C/HDL-C ratio is associated with the presence of carotid atherosclerosis in post-menopausal women and is strongly correlated to VLDL-C levels.

Plasma atherogenic indices are independent predictors of slow coronary flow

Background Although the pathophysiology of coronary slow flow (CSF) has not been fully elucidated, emerging data increasingly support potential role for subclinical diffuse atherosclerosis in the etiology of CSF. We aimed to investigate relationship between atherogenic indices and CSF. Methods 130 patients with CSF diagnosed according to Thrombolysis in Myocardial Infarction (TIMI)-frame count (TFC) method and 130 controls who had normal coronary flow (NCF) were included in this retrospective study. Atherogenic indices (atherogenic index of plasma [AIP], Castelli risk indices I and II [CRI-I and II]) were calculated using conventional lipid parameters. Results The logistic regression analyses demonstrated that AIP (OR, 5.463; 95% confidence interval [CI], 1.357–21.991; p = 0.017) and CRI-II (OR, 1.624; 95% CI, 1.138–2.319; p = 0.008) were independent predictors of CSF. Receiver operating characteristic analysis showed that the optimal cutoff value to predict the occurrence of CSF was 0.66 for AIP (sensitivity, 59%; specificity, 73%; area under curve [AUC], 0.695; p < 0.001) and 3.27 for CRI-II (sensitivity, 60%; specificity, 79%; AUC, 0.726; p < 0.001). Conclusions AIP and CRI-II levels were independent predictors of CSF. Prospective studies in larger cohorts of patients may elucidate the role of atherogenic dyslipidemia in the pathophysiology of CSF.

Pregnane-Oximino-Alkyl-Amino-Ether Compound as a Novel Class of TGR5 Receptor Agonist Exhibiting Antidiabetic and Anti-Dyslipidemic Activities

<b><i>Introduction:</i></b> The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models. <b><i>Methods:</i></b> The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic <i>db</i>/<i>db</i> mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively. <b><i>Results:</i></b> From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound <b>14b)</b> improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic <i>db</i>/<i>db</i> mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound <b>14b</b> treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound <b>14b</b> decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound <b>14b</b> were associated with the activation of the G-protein-coupled bile acid receptor TGR5. <b><i>Conclusion:</i></b> Compound <b>14b</b> exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.

Partial Clinical Remission Reduces Lipid-Based Cardiovascular Risk in Adult Patients With Type 1 Diabetes

ImportanceRisk factors for atherosclerotic cardiovascular disease (ASCVD) are well established in type 2 diabetes (T2D), but not in type 1 diabetes (T1D). The impact of partial clinical remission (PR) on short-term ASCVD risk in T1D is unclear.AimTo investigate the impact of PR on the earliest ASCVD risk phenotype in adult T1D using factor analysis to compare the lipid phenotypes of T1D, T2D and controls after stratifying the T1D cohort into remitters and non-remitters.Subjects and MethodsA study of 203 adults subjects consisting of 86 T2D subjects, and 77 T1D subjects stratified into remitters (n=49), and non-remitters (n=28). PR was defined as insulin-dose adjusted HbA1c of ≤9, and obesity as a BMI ≥30 kg/m2. Factor analysis was used to stratify the groups by ASCVD risk by factorizing seven lipid parameters (TC, LDL, HDL, non-HDL, TC/HDL, TG, TG/HDL) into 2 orthogonal factors (factor 1: TC*LDL; factor 2: HDL*TG) that explained 90% of the variance in the original seven parameters.ResultsThe analysis of individual lipid parameters showed that TC/HDL was similar between the controls and remitters (p=NS) but was significantly higher in the non-remitters compared to the remitters (p=0.026). TG/HDL was equally similar between the controls and remitters (p=NS) but was lower in the remitters compared to the non-remitters (p=0.007). TG was significantly lower in the remitters compared to T2D subjects (p&lt;0.0001) but was similar between T2D subjects and non-remitters (p=NS). Non-HDL was significantly lower in the controls versus non-remitters (p=0.0003) but was similar between the controls and remitters (p=NS). Factor analysis showed that the means of factor 1 and factor 2 composite scores for dyslipidemia increased linearly from the controls, remitters, non-remitters to T2D, p value 0.0042 for factor 1, and &lt;0.0001 for factor 2, with remitters having similar lipid phenotype as controls, while non-remitters were similar to T2D.ConclusionsPartial clinical remission of T1D is associated with a favorable early lipid phenotype which could translate to reduced long-term CVD risk in adults.

Research on physical activity variability and changes of metabolic profile in patients with prediabetes using Fitbit activity trackers data

BACKGROUND: Monitoring physical activity with consumers wearables is one of the possibilities to control a patient’s self-care and adherence to recommendations. However, clinically approved methods, software, and data analysis technologies to collect data and make it suitable for practical use for patient care are still lacking. OBJECTIVE: This study aimed to analyze the potential of patient physical activity monitoring using Fitbit physical activity trackers and find solutions for possible implementation in the health care routine. METHODS: Thirty patients with impaired fasting glycemia were randomly selected and participated for 6 months. Physical activity variability was evaluated and parameters were calculated using data from Fitbit Inspire devices. RESULTS: Changes in parameters were found and correlation between clinical data (HbA1c, lipids) and physical activity variability were assessed. Better correlation with variability than with body composition changes shows the potential to include nonlinear variability parameters analysing physical activity using mobile devices. Less expressed variability shows better relationship with control of prediabetic and lipid parameters. CONCLUSIONS: Evaluation of physical activity variability is essential for patient health, and these methods used to calculate it is an effective way to analyze big data from wearable devices in future trials.

Egg consumption and blood lipid parameters according to the presence of chronic metabolic disorders: The EVIDENT II Study

Context Egg consumption is one of the main dietary sources of cholesterol, but whether individuals who eat more eggs have a worse blood lipid profile remains controversial. Objective We examined the relationship between egg consumption and lipid parameters and explored whether this relationship changes according to the presence of chronic metabolic disorders. Methods A multicenter cross-sectional study was conducted with adult participants in the EVIDENT II trial. Adjusted linear regression models were stratified by the main chronic metabolic disorders. Results Among the 728 participants (61.9% women, mean age 52.1±11.9 years), the mean egg consumption was equivalent to 5-to-6 eggs per week for a 70 kg individual. In the fully-adjusted analysis, no association was found of egg consumption with total and HDL cholesterol, and triglyceride levels. Furthermore, compared to the first quartile of consumption, the fourth quartile was associated with lower LDL-c levels (coefficient: -7.01; 95%CI: -13.39, -0.62) and a lower LDL-c/HDL-c ratio (coefficient: -0.24, 95%CI: -0.41, -0.06). In the analyses stratified by chronic metabolic diseases, higher egg consumption was not associated with lipid profile in those with obesity, hypertension, type 2 diabetes, dyslipidemia, or treated with hypolipidemic drugs, and was associated with a better lipid profile in participants without these conditions. Conclusions Higher egg consumption was not associated with blood lipids in individuals with chronic metabolic disorders. In individuals without such conditions, the lipid profile was better among those who consumed more eggs. Our findings support current guidelines recommending eggs as part of a healthy diet.

Study on impact of silver nanoparticles synthesized using aqueous extract of Ganoderma applanatum on thyroid and lipid parameters of albino rat

Se estudió el impacto de SNP cargadas con extracto de Ganoderma applanatum sobre el perfil tiroideo y lipídico de rata. Las SNP (diámetro medio 58,77 nm; potencial zeta - 3,8) mV se analizaron mediante DLS. La microespectroscopía de infrarrojo con transformada de Fourier proporcionó un pico de transmisión amplio y elevado a 3248,12 cm-1, que indica la carga bioquímica del extracto de G. applanatum en la superficie de los SNP. No se observó mortalidad ni cambios de comportamiento en la prueba de toxicidad aguda. El grupo-1 recibió 1 mL de agua destilada, el grupo-2 y el grupo-3 recibieron 200 mg kg-1 y 400 mg kg-1 de nanopartículas respectivamente. Una dosis de 400 mg kg-1 de SNPs mostró una mayor actividad hipertiroidea e hipolipidímica en comparación con el control y la dosis de 200 mg kg-1. Impact of silver nanoparticles loaded with Ganoderma applanatum extract on thyroid and lipid profile of rat were studied. Synthesized SNPs (Average diameter 58.77 nm; -13.8 mV zeta potential) were analysed by dynamic light scattering analysis. Fourier transform infrared spectroscopy provided broad and high transmission peak at 3248.12 cm-1 which indicates the loaded biochemical of the G. applanatum extract on the surface of SNPs. No mortality and behavioural changes were observed in the Acute toxicity test. Group-1 received 1 mL distilled water, group-2 and group-3 received 200 mg kg-1 and 400 mg kg-1 nanoparticles respectively. A 400 mg kg-1 dose of SNPs showed increased hyper thyroid and hypolipidimic activity as compared to control and 200 mg kg-1 dose.