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Frontiers in Molecular Biosciences 2021Periodontitis is an inflammatory disorder caused by disintegration of the balance between the periodontal microbiome and host response. While growing evidence suggests...
Periodontitis is an inflammatory disorder caused by disintegration of the balance between the periodontal microbiome and host response. While growing evidence suggests links between periodontitis and various metabolic disorders including type 2 diabetes (T2D), non-alcoholic liver disease, and cardiovascular disease (CVD), which often coexist in individuals with abdominal obesity, factors linking periodontal inflammation to common metabolic alterations remain to be fully elucidated. More detailed characterization of metabolomic profiles associated with multiple oral and cardiometabolic traits may provide better understanding of the complexity of oral-systemic crosstalk and its underlying mechanism. We performed comprehensive profiling of plasma and salivary metabolomes using untargeted gas chromatography/mass spectrometry to investigate multivariate covariation with clinical markers of oral and systemic health in 31 T2D patients with metabolic comorbidities and 30 control subjects. Orthogonal partial least squares (OPLS) results enabled more accurate characterization of associations among 11 oral and 25 systemic clinical outcomes, and 143 salivary and 78 plasma metabolites. In particular, metabolites that reflect cardiometabolic changes were identified in both plasma and saliva, with plasma and salivary ratios of (mannose + allose):1,5-anhydroglucitol achieving areas under the curve of 0.99 and 0.92, respectively, for T2D diagnosis. Additionally, OPLS analysis of periodontal inflamed surface area (PISA) as the numerical response variable revealed shared and unique responses of metabolomic and clinical markers to PISA between healthy and T2D groups. When combined with linear regression models, we found a significant correlation between PISA and multiple metabolites in both groups, including threonate, cadaverine and hydrocinnamate in saliva, as well as lactate and pentadecanoic acid in plasma, of which plasma lactate showed a predominant trend in the healthy group. Unique metabolites associated with PISA in the T2D group included plasma phosphate and salivary malate, while those in the healthy group included plasma gluconate and salivary adenosine. Remarkably, higher PISA was correlated with altered hepatic lipid metabolism in both groups, including higher levels of triglycerides, aspartate aminotransferase and alanine aminotransferase, leading to increased risk of cardiometabolic disease based on a score summarizing levels of CVD-related biomarkers. These findings revealed the potential utility of saliva for evaluating the risk of metabolic disorders without need for a blood test, and provide evidence that disrupted liver lipid metabolism may underlie the link between periodontitis and cardiometabolic disease.
PubMed: 34589520
DOI: 10.3389/fmolb.2021.742002 -
Annals of Nuclear Medicine Nov 2022This study aimed to optimize various methods of calculating washout rates (WRs) of I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose...
OBJECTIVE
This study aimed to optimize various methods of calculating washout rates (WRs) of I-β-methyl-p-iodophenyl-pentadecanoic (BMIPP), as they are essential to diagnose triglyceride deposit cardiomyovasculopathy (TGCV) which is a rare disease entity identified in Japan and has been encoded in Orphanet (ORPHA code 565612).
METHODS
We calculated WRs of I-BMIPP from early (20 min) and delayed (200 min) images. We evaluated six methods of calculating WRs to discriminate TGVC patients (age, 56.8 ± 14.6 y; male, n = 13; female, n = 4) and 21 I-BMIPP studies were involved including 4 follow-up studies. Washout rates were calculated by two planar methods using anterior images with cardiac and background regions of interest (ROIs) and by four SPECT methods using either array and polar plots or summed short-axis images. The final diagnoses of TGCV were confirmed according to the 2020 diagnostic criteria, and the diagnostic accuracy of WRs calculated using the six methods was analyzed using the area under receiver-operating characteristics curves (ROC-AUC). Multiple scatter-plot matrix methods were evaluated with correlations for comparison.
RESULTS
All six methods were useful for diagnosis and did not significantly differ. The four SPECT methods showed excellent diagnostic accuracy (AUC 1.0), whereas the planar methods with and without background correction could be acceptable (AUC 0.857 and 0.964, respectively). The WRs were relatively lower for patients with CAD and remarkable metabolic defects than for patients with TGCV but without defects.
CONCLUSIONS
For the diagnosis of TGCV, the WR cutoff of 10% of I-BMIPP functioned well in planar and SPECT discrimination based on computational methods as a classifier. However, calculation optimization should improve TGCV diagnoses.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Triglycerides; Iodobenzenes; Fatty Acids; Tomography, Emission-Computed, Single-Photon; Myocardium
PubMed: 36155888
DOI: 10.1007/s12149-022-01787-9 -
PloS One 2017Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty...
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn't affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.
Topics: Animals; Choline; Choline Deficiency; Disease Models, Animal; Fatty Acids; Hepatocytes; Humans; Liver; Methionine; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Triglycerides
PubMed: 29244873
DOI: 10.1371/journal.pone.0189965 -
Journal of Imaging Oct 2022(1) Background: The mortality of breast cancer has decreased due to the advancement of cancer therapies. However, more patients are suffering from...
Iodine-123 β-methyl-P-iodophenyl-pentadecanoic Acid (I-BMIPP) Myocardial Scintigraphy for Breast Cancer Patients and Possible Early Signs of Cancer-Therapeutics-Related Cardiac Dysfunction (CTRCD).
(1) Background: The mortality of breast cancer has decreased due to the advancement of cancer therapies. However, more patients are suffering from cancer-therapeutics-related cardiac dysfunction (CTRCD). Diagnostic and treatment guidelines for CTRCD have not been fully established yet. Ultrasound cardiogram (UCG) is the gold standard for diagnosis of CTRCD, but many breast cancer patients cannot undergo UCG due to the surgery wounds or anatomical reasons. The purpose of the study is to evaluate the usefulness of myocardial scintigraphy using Iodine-123 β-methyl-P-iodophenyl-pentadecanoic acid (I-BMIPP) in comparison with UCG. (2) Methods: 100 breast cancer patients who received chemotherapy within 3 years underwent Thallium (Tl) and I-BMIPP myocardial perfusion and metabolism scintigraphy. The images were visually evaluated by doctors and radiological technologists, and the grade of uptake reduction was scored by Heart Risk View-S software (Nihon Medi-Physics). The scores were deployed in a 17-segment model of the heart. The distribution of the scores were analyzed. (3) Results: Nine patients (9%) could not undergo UCG. No correlation was found between left ventricular ejection fraction (LVEF) and Heart Risk View-S scores of Tl myocardial perfusion scintigraphy nor those of BMIPP myocardial metabolism scintigraphy. In a 17-segment model of the heart, the scores of the middle rings were higher than for the basal ring. (4) Conclusions: Evaluation by UCG is not possible for some patients. Myocardial scintigraphy cannot serve as a perfect alternative to UCG. However, it will become the preferable second-choice screening test, as it could point out the early stage of CTRCD.
PubMed: 36354869
DOI: 10.3390/jimaging8110296 -
The American Journal of Clinical... Dec 2022Circulating individual SFAs in pregnant females are critical for maternal and fetal health. However, research on identifying their modifiable factors is limited. (Clinical Trial)
Clinical Trial
BACKGROUND
Circulating individual SFAs in pregnant females are critical for maternal and fetal health. However, research on identifying their modifiable factors is limited.
OBJECTIVES
We aimed to examine the associations of total physical activity (PA) and types of PA with circulating individual SFAs during pregnancy in a multiracial/multiethnic cohort of pregnant females in the United States.
METHODS
The study included participants in a nested case-control study (n = 321) from the Eunice Kennedy Shriver NICHD Fetal Growth Studies-Singleton Cohort. Sampling weights were applied, so the results represented the entire Fetal Growth Cohort. Plasma phospholipid SFAs were measured at 4 visits [10-14 (visit 1), 15-26 (visit 2), 23-31 (visit 3), and 33-39 (visit 4) weeks of gestation] throughout pregnancy. PA of the previous year at visit 1 and since the previous visit at the subsequent visits was assessed using the validated Pregnancy PA Questionnaire. Time-specific and longitudinal associations were examined using multivariable linear and generalized estimating equation models.
RESULTS
Total PA (metabolic equivalent of task-h/wk) was positively associated with circulating heptadecanoic acid (17:0) at visit 1 (β × 103: 0.07; 95% CI: 0.02, 0.11) and pentadecanoic acid (15:0) at visit 3 (β × 103: 0.09; 95% CI: 0.03, 0.14) independent of sociodemographic, reproductive, pregnancy, and dietary factors. Across the 4 visits, the positive associations with total PA were consistent for pentadecanoic acid (β × 103: 0.06; 95% CI: 0.02, 0.10) and heptadecanoic acid (β × 103: 0.10; 95% CI: 0.06, 0.14). Out of the 4 PA types (i.e., sports/exercise, household/caregiving, transportation, and occupational PA) considered, the magnitude of positive associations was the largest for sports/exercise PA.
CONCLUSIONS
Our findings suggest that maternal PA is positively associated with circulating pentadecanoic and heptadecanoic acids. The findings warrant confirmation by future studies.This trial was registered at clinicaltrials.gov as NCT00912132.
Topics: Female; Humans; Pregnancy; Exercise; Longitudinal Studies; Phospholipids; Prospective Studies; United States
PubMed: 36373403
DOI: 10.1093/ajcn/nqac250 -
Molecules (Basel, Switzerland) Mar 2023The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two...
The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two endophytic fungal strains were isolated from roots and identified as MT597434.1 and KU324798.1. Secondary metabolites produced by and were extracted and tested for their antimicrobial activity. The highest activity was noticed against and treated with and secondary metabolites, respectively. crude extract was mainly composed of Pentadecanoic acid, 14-methyl-, methyl ester and 9-Octadecenoic acid ()-, methyl ester (26.66 and 18.01%, respectively), while crude extract's major components were 2,4-Decadienal, (,) and 9-Octadecenoic acid ()-, and methyl ester (10.69 and 10.32%, respectively). Moreover, a comparative study between the fungal extracts and dicationic pyridinium iodide showed that the combination of and secondary metabolites with dicationic pyridinium iodide compound showed a synergistic effect against . The combined formulae inhibited the bacterial growth after 4 to 6 h through cell wall breakage and cells deformation, with intracellular components leakage and increased ROS production.
Topics: Iodides; Escherichia coli; Oleic Acid; Aspergillus niger; Complex Mixtures
PubMed: 36985405
DOI: 10.3390/molecules28062434 -
The Chinese Journal of Physiology 2023Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0%...
Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Chromatography, Liquid; Prospective Studies; Tandem Mass Spectrometry; Metabolome; Myocardium; Carbohydrates
PubMed: 38149568
DOI: 10.4103/cjop.CJOP-D-23-00126 -
The American Journal of Clinical... Dec 2014Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk. However, observational studies have reported inconsistent results, and...
BACKGROUND
Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk. However, observational studies have reported inconsistent results, and few have examined dairy's association with the underlying disorders of insulin resistance and β-cell dysfunction.
OBJECTIVE
We investigated the association of the dairy fatty acid biomarkers pentadecanoic acid (15:0) and trans-palmitoleic acid (trans 16:1n-7) with type 2 diabetes traits by evaluating 1) prospective associations with incident diabetes after 5 y of follow-up and 2) cross-sectional associations with directly measured insulin resistance and β-cell dysfunction.
DESIGN
The study analyzed 659 adults without diabetes at baseline from the triethnic multicenter Insulin Resistance Atherosclerosis Study (IRAS). Diabetes status was assessed by using oral-glucose-tolerance tests. Frequently sampled intravenous-glucose-tolerance tests measured insulin sensitivity (SI) and β-cell function [disposition index (DI)]. Serum fatty acids were quantified by using gas chromatography. Logistic and linear regression models were adjusted for demographic, lifestyle, and dietary variables.
RESULTS
Serum 15:0 was a significant biomarker for total dairy intake in the IRAS cohort. It was associated with a decreased incident diabetes risk (OR: 0.73, P = 0.02) and was positively associated with log SI (β: 0.84, P = 0.03) and log DI (β: 2.21, P = 0.02) in fully adjusted models. trans 16:1n-7 was a marker of total partially hydrogenated dietary fat intake and was not associated with outcomes in fully adjusted models.
CONCLUSIONS
Serum 15:0, a marker of short-term intake of this fatty acid, was inversely associated with diabetes risk in this multiethnic cohort. This study may contribute to future recommendations regarding the benefits of dairy products on type 2 diabetes risk.
Topics: Adult; Biomarkers; Blood Glucose; Cross-Sectional Studies; Dairy Products; Diabetes Mellitus, Type 2; Dietary Fats; Ethnicity; Fatty Acids; Fatty Acids, Monounsaturated; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Life Style; Linear Models; Logistic Models; Male; Middle Aged; Prospective Studies
PubMed: 25411288
DOI: 10.3945/ajcn.114.092544 -
Open Life Sciences Jan 2019The aetiology of polycystic ovary syndrome (PCOS) remains uncertain and thus dedicated studies are still of much importance. Patients in this group are at high risk for...
Decrease in the Level of Nervonic Acid and Increased Gamma Linolenic Acid in the Plasma of Women with Polycystic Ovary Syndrome after a Three-month Low-glycaemic Index and Caloric Reduction Diet.
The aetiology of polycystic ovary syndrome (PCOS) remains uncertain and thus dedicated studies are still of much importance. Patients in this group are at high risk for metabolic syndrome, diabetes and ischemic heart disease. Our goal was to use a dietary intervention, facilitating the regression of the disease, through the observation of lipid and hormonal profiles, carbohydrate metabolic parameters and metabolomics of plasma fatty acids. There were 39 Caucasian women with PCOS aged 26.76 ±5.08 that qualified for this study. Fatty acid profiles were investigated using gas chromatography. The results of plasma fatty acids were compared with the initial results and the control group. A three-month caloric reduction diet with low glycemic index (GI) reduces the level of nervonic acid and is a great alternative in PCOS therapy. The introduction of rapeseed oil and olive oil to the lowered GI reduction diet caused the increase in the ratio of average length chain fatty acids (C10:0, C14:0) and the enhancement of synthesis pathways for pentadecanoic acid (C15:0) and gamma-linolenic acid (GLA, C18:3n-6), but did not inhibit the synthesis of the derivatives of arachidic acid (C20:0). Additionally, a decrease in the level of nervonic acid (C24:1) was observed. Biochemical analysis of blood showed the improvement of plasma lipid fractions, but a significant reduction of androgen levels was not observed. A reduction diet with lowered GI lead to many positive effects in the improvement of the biochemical parameters of women with PCOS. It should be continued for a prolonged period of time, until the synthesis pathways for inflammatory factors are silenced.
PubMed: 33817156
DOI: 10.1515/biol-2019-0026 -
International Journal of Clinical... Apr 2013A Malabsorption Blood Test (MBT) is proposed as an alternative method to the 72-hour stool and dietary collection for assessing the degree of fat malabsorption in people...
Diagnosing malabsorption with systemic lipid profiling: pharmacokinetics of pentadecanoic acid and triheptadecanoic acid following oral administration in healthy subjects and subjects with cystic fibrosis.
OBJECTIVE
A Malabsorption Blood Test (MBT) is proposed as an alternative method to the 72-hour stool and dietary collection for assessing the degree of fat malabsorption in people with pancreatic insufficiency. The MBT consists of a simultaneous oral dose of pentadecanoic acid (PA), a free fatty acid, and triheptadecanoic acid (THA), a triglyceride with three heptadecanoic (HA) saturated fatty acids requiring hydrolysis by pancreatic lipase before HA can be intestinally absorbed. The aim of this study is to demonstrate the ability of MBT to detect fat malabsorption in healthy adult subjects using the pancreatic lipase (PL) inhibitor Orlistat (Xenical®), and in subjects with CF and PI while on and off routine pancreatic enzyme doses.
MATERIALS AND METHODS
The MBT with the PA and THA were delivered in a breakfast test meal (2.5 g PA and either 5 g or 8 g THA) to healthy adult subjects (ages 18 - 50 years, BMI 21 - 30) and to subjects with CF (> 12 years, FEV1% predicted > 40%), after a 12-hour fast and 24 hours without dairy foods. Serum levels of PA and HA were assessed by gas-liquid chromatography, from blood samples drawn prior to MBT and then hourly for 8 hours. For healthy subjects, the MBT was administered before and after Orlistat treatment, and in subjects with CF, both with subjects receiving routine pancreatic lipase treatment ("on enzyme") and also "off enzyme" treatment. Treatment groups were compared for baseline (C0) and maximum (Cmax) plasma concentrations of PA and HA over 8 hours: area under the curve (AUC) was calculated using linear trapezoid method. The ratio of HA to PA Cmax and AUC was also calculated and compared.
RESULTS
For the healthy subjects (n = 15, 60% female, ages 21 - 49 years), absorption of HA was reduced 71% for Cmax (p < 0.001) and 65% for AUC (p = 0.001) after Orlistat treatment, and absorption of PA was unchanged. For subjects with CF (n = 6, 50% female, ages 13 - 19 years), absorption of HA was minimal with subjects "off enzymes" and increased significantly with subjects "on enzymes" while absorption of PA did not differ between groups. Enzyme administration resulted in increased Cmax HA/ PA ratios from 0.02 to 0.92 and from 0.05 to 0.73 in subjects with CF receiving 5.0 g and 8.0 g of THA, respectively. AUC HA/PA ratios showed similar increases.
CONCLUSIONS
In this pilot and feasibility proof-of-concept study, the MBT, utilizing the relative absorption of HA to PA, two odd-chained fatty acids, responds to changes in fat absorption in healthy subjects using a lipase inhibitor and in subjects with CF while on or off enzyme therapy. The MBT holds promise to provide a more accurate, specific and acceptable alternative to the 72-hour stool collection to quantify pancreatic-based fat malabsorption in a variety of clinical and research contexts.
Topics: Administration, Oral; Adolescent; Adult; Area Under Curve; Chromatography, Gas; Cystic Fibrosis; Dietary Fats; Fatty Acids; Feasibility Studies; Female; Humans; Lactones; Malabsorption Syndromes; Male; Middle Aged; Orlistat; Pilot Projects; Young Adult
PubMed: 23357842
DOI: 10.5414/CP201793