Browsing by Subject "lipids"

Now showing 1 - 7 of 7
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    Bariatric Surgery–Induced Cardiac and Lipidomic Changes in Obesity‐Related Heart Failure with Preserved Ejection Fraction
    (Wiley, 2018) Mikhalkova, Deana; Holman, Sujata R.; Jiang, Hui; Sagir, Mohammed; Novak, Eric; Coggan, Andrew R.; O'Connor, Robert; Bashir, Adil; Jamal, Ali; Ory, Daniel S.; Schaffer, Jean E.; Eagon, J. Christopher; Peterson, Linda R.; Kinesiology, School of Physical Education and Tourism Management
    Objective To determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF). Methods A primary cohort (N = 12) with HFpEF and obesity underwent echocardiography and magnetic resonance spectroscopy both before and 3 months and 6 months after bariatric surgery. Plasma lipidomic analysis was performed before surgery and 3 months after surgery in the primary cohort and were confirmed in a validation cohort (N = 22). Results After surgery‐induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, P < 0.001, and P = 0.007, respectively); echo‐derived e′ increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate. Conclusions Surgery‐induced weight loss in women with HFpEF and obesity was associated with improved symptoms, reverse cardiac remodeling, and improved relaxation. Although weight loss was associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. The results of this study suggest that gastric bypass ameliorates obesity‐related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.
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    Effect of Depression Treatment on Health Behaviors and Cardiovascular Risk Factors Among Primary Care Patients with Depression: Data from the eIMPACT Trial
    (2023-12) Schuiling, Matthew D.; Stewart, Jesse; Hirsh, Adam; Wu, Wei
    Background. Although depression is a risk factor for cardiovascular disease (CVD), few clinical trials in people without CVD have examined the effect of depression treatment on CVD-related outcomes. It’s unknown if successful depression treatment improves indicators of CVD risk, such as CVD-relevant health behaviors, traditional CVD risk factors, and CVD events. Methods. We examined data from eIMPACT trial, a phase II randomized controlled trial conducted from 2015-2020. Depressive symptoms, CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed. Incident CVD events over four years were identified using a statewide health information exchange. Results. The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). CVD-relevant health behaviors did not mediate any intervention effects on traditional CVD risk factors. Twenty-two participants (10%) experienced an incident CVD event. The likelihood of an CVD event did not differ between the intervention group (12.1%) and the usual care group (8.3%; HR = 1.45, 95% CI: 0.62-3.40, p = 0.39). Conclusions. Successful depression treatment alone improves self-reported sleep quality but is not sufficient to lower CVD risk of people with depression. Alternative approaches may be needed reduce CVD risk in depression. Trial Registration: ClinicalTrials.gov Identifier: NCT02458690
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    Interaction of Model Lipid Vesicles with Alveolar Macrophages
    (Office of the Vice Chancellor for Research, 2014-04-11) Maasa, Robinah K.; Justice, Matthew J.; Petrusca, Daniela N.; Petrache, Horia I.
    Macrophages are a type of white blood cells that play key roles in host defense by recognizing and engulfing foreign and apoptotic bodies. To accomplish this task, they rely on complex molecular interactions involving both lipids and proteins. Previous studies have shown that surface exposure of phosphatidylserine by apoptotic cells is required for their successful clearance, suggesting specific lipid-protein interactions at least for the initiation of phagocytosis of apoptotic cells. However, macrophages can engulf foreign and apoptotic bodies that substantially vary in size suggesting that non-specific interactions over a range of length scales may be relevant. The purpose of our study is to investigate the correlation between physical properties of lipid bilayers and their engulfment by macrophages. We modify bilayer properties systematically as a function of phospholipid headgroup composition and by addition of ceramide and cholesterol. We use a combination of scattering and spectroscopic methods to quantify lipid interactions and flow cytometry to measure engulfment rates. This study can help distinguish between the role of lipids and proteins in clearance of apoptotic and foreign particles.
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    Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry
    (National Academy of Sciences, 2017-06-27) Pirro, Valentina; Alfaro, Clint M.; Jarmusch, Alan K.; Hattab, Eyas M.; Cohen-Gadol, Aaron A.; Cooks, R. Graham; Pathology and Laboratory Medicine, School of Medicine
    Gliomas infiltrate into surrounding healthy brain tissue. Microsurgical resection aims for maximal tumor resection while minimizing morbidity. Surgical margins are defined based on the surgeon’s experience, visual observation, and neuronavigation. Surgical margin assessment is rarely undertaken intraoperatively due to time constraints and unreliability of such evaluation. Routine, pathologic intraoperative examination provides no molecular information. Molecular measurements using mass spectrometry can be made rapidly on tissue during surgery to identify tissue types, estimate tumor infiltration, and recognize the presence of prognostic mutations by monitoring oncometabolites and phospholipids. This intraoperative study demonstrates the power of mass spectrometry in assessing diagnostic and prognostic information on discrete surgeon-defined points along the resection margins to improve tumor resection, even in regions without MRI contrast enhancement., Intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS) is used to characterize tissue smears by comparison with a library of DESI mass spectra of pathologically determined tissue types. Measurements are performed in the operating room within 3 min. These mass spectra provide direct information on tumor infiltration into white or gray brain matter based on N-acetylaspartate (NAA) and on membrane-derived complex lipids. The mass spectra also indicate the isocitrate dehydrogenase mutation status of the tumor via detection of 2-hydroxyglutarate, currently assessed postoperatively on biopsied tissue using immunohistochemistry. Intraoperative DESI-MS measurements made at surgeon-defined positions enable assessment of relevant disease state of tissue within the tumor mass and examination of the resection cavity walls for residual tumor. Results for 73 biopsies from 10 surgical resection cases show that DESI-MS allows detection of glioma and estimation of high tumor cell percentage (TCP) at surgical margins with 93% sensitivity and 83% specificity. TCP measurements from NAA are corroborated by indirect measurements based on lipid profiles. Notably, high percentages (>50%) of unresected tumor were found in one-half of the margin biopsy smears, even in cases where postoperative MRI suggested gross total tumor resection. Unresected tumor causes recurrence and malignant progression, as observed within a year in one case examined in this study. These results corroborate the utility of DESI-MS in assessing surgical margins for maximal safe tumor resection. Intraoperative DESI-MS analysis of tissue smears, ex vivo, can be inserted into the current surgical workflow with no alterations. The data underscore the complexity of glioma infiltration.
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    Maternal lipid profile differs by gestational diabetes physiologic subtype
    (Elsevier, 2019-02) Layton, Jill; Powe, Camille; Allard, Catherine; Battista, Marie-Claude; Doyon, Myriam; Bouchard, Luigi; Perron, Patrice; Wessel, Jennifer; Hivert, Marie-France; Epidemiology, School of Public Health
    Aim To characterize lipid profiles in women with different gestational diabetes mellitus (GDM) physiologic subtypes. Methods We measured seven lipid markers (total cholesterol, LDL, HDL, triglycerides, non-esterified fatty acids (NEFA), ApoA, ApoB) in fasting plasma collected in a prospective cohort of 805 pregnant women during second trimester. We estimated insulin sensitivity and secretion using oral glucose tolerance test-based validated indices. We categorized GDM physiologic subtypes by insulin sensitivity and secretion defects defined as values below the 25th percentile among women with normal glucose tolerance (NGT), as previously established. We compared lipid markers across NGT and GDM subtypes. We explored associations between lipid markers and newborn anthropometry in the overall group and stratified by glucose tolerance status. Results Among 805 women, 67 (8.3%) developed GDM. Women with GDM had higher body mass index (BMI; 29.3 vs. 26.6 kg/m2), while ethnicity (97.3% vs. 97.0% European ancestry) and age (28 vs. 29 years) were similar. In comparison to women with NGT, women with GDM characterized by a predominant insulin sensitivity defect had significantly higher triglycerides (2.20 vs. 1.82, P = 0.002), lower HDL (1.64 vs. 1.90, P = 0.01) and higher NEFA (0.34 vs. 0.24, P < 0.0001). GDM women with a predominant insulin secretion defect differed from women with NGT with respect to NEFA (0.32 vs. 0.24, P = 0.003) while other lipid markers were similar. These associations remained significant after adjusting for maternal age and BMI. Greater maternal levels of NEFA were associated with higher birth weight z-scores in women with an insulin secretion defect (BMI-adjusted r = 0.58, P = 0.01). We did not find significant associations between other lipid markers and newborn anthropometry in other groups. Conclusion Women with GDM have distinct lipid profiles based on their GDM physiologic subtype which may not be apparent when investigating GDM as a single group.
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    Serum phospholipid fraction of polyunsaturated fatty acids is the preferred indicator for nutrition and health status in hemodialysis patients
    (Elsevier, 2016-12) Watkins, Bruce A.; Kim, Jeffrey; Tamez, Hector; Wenger, Julia; Thadhani, Ravi; Friedman, Allon N.; Department of Medicine, IU School of Medicine
    Long chain (LC) polyunsaturated fatty acids (PUFA) are major components of cell membrane phospholipids (PL) and serve as precursors for numerous bioactive lipid derivatives. Fatty acids (FA) are routinely analyzed in biological samples to assess composition of tissues, cells, and lipid fractions. In human studies, serum or plasma is often used because of their easy procurement. However, the lipid pool in serum and plasma is a mixture of triacylglycerol (TG), PL, cholesterol and its esters, and other components. Herein, we report findings from a serum FA analysis after fractionation of polar and neutral lipids by solid phase extraction in a large cohort of 400 hemodialysis patients. LC PUFA were found concentrated in the polar fraction compared to the total or the neutral lipid fraction. When correlated with clinical markers of disease, a greater number of significant correlations were found for PUFA in polar compared to total or the neutral fraction. We also observed that polar lipids are a reliable reflection of LC PUFA status compared to the total or neutral fractions because the latter are diluted by non-essential FA. The relative amounts of LC PUFA in the total and neutral fractions reflect the contribution of TG in blood that varies with diet, age, and physiologic state. Our data indicate that LC PUFA in the polar fraction are superior indicators of bioactive FA-status than in the total or the neutral fraction and should be used to establish important links between PUFA status, their bioactive substrates in hemodialysis patients.
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    Statin use and risk of developing diabetes: results from the Diabetes Prevention Program
    (BMJ Journals, 2017-10-10) Crandall, Jill P; Mather, Kieren; Rajpathak, Swapnil N; Goldberg, Ronald B; Watson, Karol; Foo, Sandra; Ratner, Robert; Barrett-Connor, Elizabeth; Temprosa, Marinella; Medicine, School of Medicine
    Objective Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations. Research design and methods During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant’s own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits. Results At 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%–37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy. Conclusions In this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes. Trial registration number NCT00038727; Results.