Thomas V. Fungwe

The Systematic Review Methodology Used to Support the 2010 Dietary Guidelines Advisory Committee

t r s s s s t r The Dietary Guidelines for Americans (DGA) are jointly issued and updated every 5 years by the US Department of Agriculture (USDA) and the US Deartment of Health and Human Services (HHS). They rovide authoritative nutrition advice for people age 2 ears and older to promote health and reduce risk for ajor chronic diseases. To update the 2005 DGA (1), the SDA and HHS appointed a 13-member Dietary Guideines Advisory Committee (DGAC) to provide indepenent, science-based advice and recommendations that ould inform the development of the 2010 DGA. The ommittee was charged to focus their review on scientific vidence published since the 2005 DGAC report and place rimary emphasis on the development of food-based recmmendations (2). The purpose of this paper is to describe the systematic eview methodology used by the 2010 DGAC to support he development of its evidence-based conclusions and ecommendations. Strengths and opportunities for enancing the process are also presented. The USDA Nurition Evidence Library (NEL) was created to conduct ystematic reviews to inform federal nutrition policy and rograms. The NEL methodology was developed with ssistance from the Agency for Healthcare Research and uality and the American Dietetic Association and was

Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart

Rationale Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. Objective The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Methods and Results Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. Conclusions CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study

Abstract Possession of the Apolipoprotein E (APOE) gene &egr;4 allele is the most prevalent genetic risk factor for late onset Alzheimers disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain‐derived neurotrophic factor (BDNF). Notably, aerobic exercise‐induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise‐induced BDNF upregulation in an understudied population, we examined the effects of APOE&egr;4 (&egr;4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55 years and older, diagnosed with mild cognitive impairment participated in a six‐month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise‐induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between &egr;4 carriers and non‐&egr;4 carriers. A significant association between &egr;4 status and serum BDNF levels was detected. Non‐&egr;4 carriers showed a significant increase in BDNF levels at the 6 month time point while &egr;4 carriers did not. We believe we have identified a relationship between the &egr;4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no‐exercise control group will be necessary to determine the scope of this association in the general population. HighlightsOlder adult men but not women demonstrate exercise‐induced increases in VO2Max.Exercise‐induced up‐regulation of BDNF varies by APOE genotype.Muted BDNF response to physiological adaptations may explain &egr;4‐related AD risk.

Best strategies to recruit and enroll elderly Blacks into clinical and biomedical research

Background Historically, Blacks have been disproportionately underrepresented in clinical trials. Outcomes associated with low Blacks’ participation in research include poor understanding of the predictors and treatment of the disease, increasing health disparities, poor health equity, and suboptimal wellness of the nation as a whole. To address this gap in research participation, we analyzed our recruitment data to identify the most effective strategies for enrolling older Blacks in clinical trials. Methods Data used in these analyses were obtained from 3,266 potential volunteers, ages 50 or older, who completed a Mini-Mental State Exam as part of recruitment and screening for various clinical studies on Alzheimer’s disease. In order to determine the most effective strategies for engaging Blacks in clinical research, we used tests of proportion to assess significant differences in recruitment sources, counts, and percentages for optimal recruitment strategies by gender. Finally, we employed regression analyses to confirm our findings. Results Of the total 3,266 screened, 2,830 Black volunteers were identified for further analysis. Overall, more women than men (73.8% vs 26.2%) participated in our recruitment activities. However, a significantly higher proportion of men than women were engaged through family (3.86% vs 1.30%, p=0.0004) and referral sources (5.89% vs 2.59%, p=0.0005). Compared to other sources for recruitment, we encountered a higher proportion of volunteers at health fairs (42.95%), and through advertisements (14.97%). In our sample, years of education and age did not appear to influence the likelihood of an encounter, screening, and potential participation. Conclusion Our findings indicate Black men and women in our sample were predominantly recruited from health fairs and through advertisements tailored to their health needs and interests. Conversely, we mostly engaged Black men through family referrals and persons known to them, indicating a need for trust in their decision to engage study personnel and/or participate in clinical trials.

WITHDRAWN: Very low density lipoprotein receptor deficiency prevents obesity-induced cardiac lipotoxicity

This article has been withdrawn by the authors. We have become aware of errors in the construction of Figs 1 and 2. In Fig 1D, the tIRS1 immunoblot from untreated cardiomyocytes was inadvertently reused from Fig 2A of PLOS One 2016 May 19;11(5):e0155611. Also in Fig 1D, there were undeclared gel splices with no line indicating the assemblage of two parts in the pIRS1 immunoblot from insulin-stimulated cardiomyocytes. In Fig 2B, lanes 1-3 and lanes 5-7 of the actin immunoblot were mistakenly duplicated. Because some of the original data are no longer available, the authors wish to withdraw this article. However, the authors have full confidence in the findings and conclusions of this paper, and will repeat the missing immunoblots to complete the paper.

Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

Background: It is increasingly evident that high blood pressure can promote reduction in global and regional brain volumes. While these effects may preferentially affect the hippocampus, reports are inconsistent. Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we examined the relationships of hippocampal volume to pulse pressure (PPR) and systolic (SBP) and diastolic (DBP) blood pressure according to apolipoprotein (APOE) ɛ4 positivity and cognitive status. The ADNI data included 1,308 participants: Alzheimer disease (AD = 237), late mild cognitive impairment (LMCI = 454), early mild cognitive impairment (EMCI = 254), and cognitively normal (CN = 365), with up to 24 months of follow-up. Results: Higher quartiles of PPR were significantly associated with lower hippocampal volumes (Q1 vs. Q4, p = 0.034) in the CN and AD groups, but with increasing hippocampal volume (Q1, p = 0.008; Q2, p = 0.020; Q3, p = 0.017; Q4 = reference) in the MCI groups. In adjusted stratified analyses among non-APOE ɛ4 carriers, the effects in the CN (Q1 vs. Q4, p = 0.006) and EMCI groups (Q1, p = 0.002; Q2, p = 0.013; Q3, p = 0.002; Q4 = reference) remained statistically significant. Also, higher DBP was significantly associated with higher hippocampal volume (p = 0.002) while higher SBP was significantly associated with decreasing hippocampal volume in the EMCI group (p = 0.015). Conclusion: Changes in PPR, SBP, and DBP differentially influenced hippocampal volumes depending on the cognitive and APOE genotypic categories.

EFFECTS OF EXERCISE ON PLASMA NITRITE/NITRATE LEVELS, AND NITRIC OXIDE SYNTHASE ACTIVITY IN ELDERLY AFRICAN AMERICANS WITH MILD COGNITIVE IMPAIRMENT

P3-187 EFFECTS OF EXERCISE ON PLASMA NITRITE/NITRATE LEVELS, AND NITRIC OXIDE SYNTHASE ACTIVITY IN ELDERLY AFRICAN AMERICANS WITH MILD COGNITIVE IMPAIRMENT Oyonumo Ntekim, Julius S. Ngwa, Joanne S. Allard, Thomas V. Fungwe, Graham A. Lennox, Richard F. Gillum, Chimene Castor, Thomas O. Obisesan, Howard University, Washington, DC, USA; Howard University College of Medicine, Washington, DC, USA; Howard University, Washington, DC, USA; College of Nursing and Allied Health Sciences, Washington, DC, USA; Howard University College of Medicine, Washington DC, USA. Contact e-mail: oyonumo.ntekim@ howard.edu

Stimulation of Adipose Tissue Lipoprotein Lipase Activity Improves Glucose Metabolism and Increases High Density Lipoprotein Cholesterol in the Spontaneously Hypertensive Stroke-prone Rat

Insulin resistance syndrome (IRS), high blood pressure, elevated blood glucose and triacylglycerol-rich lipoproteins (TG-RL), as well as low levels of high-density lipoprotein (HDL-C) are disorders that combine to define metabolic syndrome (MetS). Metabolic syndrome is on the rise in the United States and is believed to be a powerful predictor of risk for diabetes and coronary events. Modulation of the activity of lipoprotein lipase (LPL) in MetS affects lipolysis of TG-RL, which has a direct correlation with the levels of plasma HDL-C. This study examined if increasing LPL activity by dietary means in a model for MetS leads to reduced IRS and increase in plasma HDL-C concentration. Ninety day-old Spontaneously Hypertensive Stroke-Prone male rats were originally fed lab chow diet for seven days. This was followed by feeding a fatty acid diet for 7 days containing one of the following: triolein (TO), trans fatty acids-rich (TFA, margarine) and 0 fatty acids (Control) with /without an LPL-rising drug (NO-1866) by gavages (5 mg or 25 mg/kg b. wt.). The results show that blood glucose and triacylglycerol levels were decreased with NO-1886. HDL-C levels increased with NO-1866 in the control and triolein group but not in the TFA group. Animals in the triolein group had higher levels of phospholipids and lower levels of insulin. Inclusion of NO-1866 lowered HOMAIR by almost 40% in the control and the TFA group, but no further reduction was observed in the TO group. The control TFA groups had up to 45% higher HOMA-IR than the TO group. Overall the data suggest that raising the activity of lipoprotein lipase by dietary means, including the feeding of monounsaturated fat may increase HDL-C, reduce plasma triacylglycerol and other indices of MetS risk, and thus may decrease the incidence of vascular complications through the normalization of lipid metabolism in subjects with MetS.

Plasma Lipid Profiles of Transgenic mice expressing the Human ApoB100XCETP are altered differentially by Diets enriched with defined Fatty Acids

Dietary fat is known to modulate plasma lipid profiles. Synthesis of high density lipoproteins (HDL), which has protective effects on vascular disease is also influenced by dietary fats, but the mechanisms are unclear. The hapoB100XCETP transgenic mouse was used to investigate the effects of fatty acids on the metabolism of plasma lipoproteins, including the pathway leading to synthesis HDL. Male transgenic mice were fed with diets formulated to provide TG (33% energy) as tripalmitin (TP), triolein (TO), tristearin (TS) or equicaloric substitution of fat with carbohydrate (sucrose) for 4 weeks. Analysis of plasma profile showed that HDL-cholesterol were 53.7+14; 64.6+8.6; 50.2+3.3; 47.0+9.2 and 45.2+4.9 mg/dL for control, oleate, palmitate, stearate and sucrose based diets, respectively. LDL-cholesterol levels were 51.7+7.0; 23.1+7.0; 38.9+2.2; 75.1+1.8 and 46.8.1.0 mg/dl, for control, TO, TP, TS and sucrose, respectively. Hepatic Lecithin-cholesterol acyltransferase (LCAT) protein levels increased by 2-fold in mice fed TS or TO diets, compared to TP, while sucrose had no effect. The scavenger receptor class B type I (SR-B1) which plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues increased in livers of animals fed TP and TO, while TS and sucrose did not have a similar effects. These results suggests that fatty acids can uniquely impact HDL, in addition, the ApoB100XCETP mouse is a useful model for the evaluation of how dietary components affect the risk of developing atherosclerosis and heart disease. key words: ApoB100, CETP, TC, HDL-C, LDL-C & TG, Transgenic.

Pulse pressure and systolic blood pressure associated with hippocampal volume by apolipoprotein (APO) carriers and Alzheimer disease status: Alzheimer’s disease neuroimaging initiative (ADNI) study

Values are m CN: Control G PRESSURE ASSOCIATEDWITH HIPPOCAMPAL VOLUME BYAPOLIPOPROTEIN (APO) CARRIERS AND ALZHEIMER DISEASE STATUS: ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI) STUDY Julius S. Ngwa, Oyonumo Ntekim, Thomas V. Fungwe, Sheree M. Johnson, Joanne S. Allard, Chimene Castor, Richard F. Gillum, Thomas O. Obisesan, Howard University College of Medicine, Washington, DC, USA; Howard University, Washington, DC,