Dietary Oxidized Linoleic Acids Modulate Fatty Acids in Mice.

Objective: An elevated concentration of oxidized lipids along with the abnormal accumulation of lipids has been linked to the formation of atheromatous plaque and the development of cardiovascular diseases. This study aims to investigate if consumption of different concentrations of dietary oxidized linoleic acid alters the distribution of long chain fatty acids (LCFAs) within the liver relative to plasma in mice. Methods: C57BL/6 male mice (n = 40) were divided into 4 groups: Standard chow as plain control (P group, n =10), Chow supplemented with linoleic acid 9 mg/mouse/day, linoleic control (C group, n=0), oxidized linoleic acid; 9 mg/mouse/day (A group, n=10) and oxidized linoleic acid 18 mg/mouse/day diet (B group, n=10). Liver and plasma samples were extracted, trans-esterified and subsequently analyzed using gas chromatography mass spectrometry (GC-MS) for LCFAs; palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid. Results: LCFA methyl esters were eluted and identified based on their respective physiochemical characteristics of GCMS assay with inter assay coefficient of variation percentage (CV%, 1.81-5.28%), limits of quantification and limit of detection values (2.021-11.402 mg/mL and 1.016-4.430 mg/mL) respectively. Correlation analysis of liver and plasma lipids of the mice groups yielded coefficients (r=0.96, 0.6, 0.8 and 0.33) with fatty acid percentage total of (16%, 10%, 16% and 58%) for the P, C, A and B groups respectively. Conclusion: The sustained consumption of a diet rich in oxidized linoleic acid disrupted fatty acid metabolism. The intake also resulted in elevated concentration of LCFAs that are precursors of bioactive metabolite molecule.

Serotonin-Affecting Antidepressant Use in Relation to Platelet Reactivity.

Depression is an independent risk factor of cardiovascular disease morbidity. Serotonin is a key neurotransmitter in depressive pathology, contained within platelets, and is a weak activator of platelets. Our study assessed the link between platelet reactivity traits, depression, and antidepressant (AD) use in a large population sample. Our study was conducted in the Framingham Heart Study (n = 3,140), and AD use (n = 563) and aspirin use (n = 681) were noted. Depression was measured using the Center for Epidemiological Studies-Depression (CES-D) survey. Platelet reactivity traits were measured across multiple agonists using five distinct assays. We utilized a linear mixed effects model to test associations between platelet traits and depression, adjusting for age, sex, aspirin use, and AD use. Similarly, we analyzed trait associations with any AD use, serotonin-affecting ADs, and norepinephrine-affecting ADs, respectively. There were strong associations with reduced platelet function and AD use, particularly with serotonin-affecting medications. This included lower Optimul epinephrine maximal aggregation (P = 4.87E-13), higher U46619 half maximal effective concentration (P = 9.09E-11), lower light transmission aggregometry (LTA) adenosine diphosphate (ADP) final aggregation (P = 1.03E-05), and higher LTA ADP disaggregation (P = 2.28E-05). We found similar associations with serotonin-affecting ADs in an aspirin-taking subset of our sample. There were no significant associations between platelet traits and depression. In the largest study yet of AD use and platelet function we show that antidepressants, particularly serotonin-affecting ADs, inhibit platelets. We did not find evidence that depressive symptomatology in the absence of medication is associated with altered platelet function. Our results are consistent with AD use leading to platelet serotonin depletions, decreased stability of platelet aggregates, and overall decreased aggregation to multiple agonists, which may be a mechanism by which ADs increase risk of bleeding and decrease risk of thrombosis.

Association between inflammation, lipopolysaccharide binding protein, and gut microbiota composition in a New Hampshire Bhutanese refugee population with a high burden of type 2 diabetes.

Introduction: South Asian refugees experience a high risk of obesity and diabetes yet are often underrepresented in studies on chronic diseases and their risk factors. The gut microbiota and gut permeability, as assessed through circulating lipopolysaccharide binding protein (LBP), may underlie the link between chronic inflammation and type 2 diabetes (T2D). The composition of the gut microbiota varies according to multiple factors including demographics, migration, and dietary patterns, particularly fiber intake. However, there is no evidence on the composition of the gut microbiota and its relationship with metabolic health in refugee populations, including those migrating to the United States from Bhutan. The objective of this study was to examine glycemic status in relation to LBP, systemic inflammation fiber intake, and gut microbiota composition in Bhutanese refugee adults residing in New Hampshire (n = 50). Methods: This cross-sectional study included a convenience sample of Bhutanese refugee adults (N = 50) in NH. Established bioinformatics pipelines for metagenomic analysis were used to determine relative genus abundance, species richness, and alpha diversity measures from shallow shotgun sequences. The relationships between inflammatory markers, gut microbiota composition, dietary fiber, and glycemic status were analyzed. Results: We identified a substantial chronic disease burden in this study population, and observed a correlation between glycemic status, LBP, and inflammation, and a correlation between glycemic status and gut microbiome alpha diversity. Further, we identified a significant correlation between proinflammatory taxa and inflammatory cytokines. SCFA-producing taxa were found to be inversely correlated with age. Conclusion: To date, this is the most comprehensive examination of metabolic health and the gut microbiome in a Bhutanese refugee population in NH. The findings highlight areas for future investigations of inflammation and glycemic impairment, in addition to informing potential interventions targeting this vulnerable population.

Berberine Encapsulated PLGA-PEG Nanoparticles Modulate PCSK-9 in HepG2 Cells.

BACKGROUND: The developments of new parenteral approaches to target PCSK-9 for the treatment of LDL-Cholesterol has yielded impressive results; and have shown significant decreases in the risk of mortality associated with hypercholesterolemia. However improved and convenient alternate approaches that exploit the beneficial drug target properties of PCSK-9 also need to be explored and developed. One such approach is the oral administration of Berberine using nanotechnology. METHODS: Nanoprecipitation encapsulation and physiochemical characterization of Berberine Chloride in PLGA-PEG-PLGA block copolymer has been developed and characterized in Hep-G2 cells using Berberine Chloride encapsulated nanoparticle (Bc-NP). Evaluation of PCSK-9, SREBP- 1, LDL-r, HNF-1alpha mRNAs and PCSK-9 protein expression was performed using quantitative real-time PCR (qPCR) and median fluorescence intensity (MFI) of flow cytometric studies respectively. Pearson's correlation analysis of PCSK-9 mRNA and protein levels in Berberine chloride delivery was performed. RESULTS: The PCSK-9 mRNA and protein expression shows a relationship to the release of Berberine from the encapsulating PLGA-PEG-PLGA polymer in a time dependent manner. CONCLUSION: PCSK-9 modulation by oral administration of Berberine using nanotechnology approach can improve its pharmacokinetic profile. Further studies are needed to maximize its delivery efficiency.

Dietary Oxidized Linoleic Acid Modulates Plasma Lipids beyond Triglycerides Metabolism.

INTRODUCTION: Triglyceride (TG) is an independent risk factor for coronary heart disease. Previous work has shown that short-term supplementations of mouse chow with oxidized linoleic acid (OxLA) significantly reduce the level of plasma triglycerides. STUDY OBJECTIVE: This study aims to determine the effects of longer-term supplementation of mouse chow with various concentrations of oxidized linoleic acid (OxLA) on plasma triglycerides. STUDY DESIGN: The study consisted of forty C57BL/6 wildtype mice divided into four groups (n = 10). Two groups were kept as controls. One control group (P) was fed plain chow and the second control group (C) was fed chow supplemented with linoleic acid. The other two experimental groups (A) and (B) were fed oxidized linoleic acid supplemented chow in the following doses: 9 mg/day of oxidized linoleic acid and 18 mg/day of oxidized linoleic acid/mouse. RESULTS AND CONCLUSION: Mice that were on a diet supplemented with the higher dose of oxidized linoleic acid showed a 39% decrease in hepatic PPAR-α and a significant decrease in the plasma HDL levels compared to the mice that were fed diets of plain and linoleic acid supplemented chow. Interestingly, the longer-term consumption of oxidized linoleic acid may predispose to atheropathogenesis.