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Furtado, Jeremy

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Furtado, Jeremy
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Now showing 1 - 10 of 18
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    Fat-soluble vitamins A and E and health disparities in a cohort of pregnant women at delivery
    (Cambridge University Press, 2018) Hanson, Corrine; Schumacher, Marina Verdi; Lyden, Elizabeth; Su, Dejun; Furtado, Jeremy; Cammack, Rex; Bereitschaft, Bradley; Van Ormer, Matthew; Needelman, Howard; McGinn, Elizabeth; Rilett, Katherine; Cave, Caleb; Johnson, Rebecca; Weishaar, Kara; Anderson-Berry, Ann
    The objective of the present study was to evaluate intakes and serum levels of vitamin A, vitamin E, and related compounds in a cohort of maternal–infant pairs in the Midwestern USA in relation to measures of health disparities. Concentrations of carotenoids and tocopherols in maternal serum were measured using HPLC and measures of socio-economic status, including food security and food desert residence, were obtained in 180 mothers upon admission to a Midwestern Academic Medical Center labour and delivery unit. The Kruskal–Wallis and independent-samples t tests were used to compare measures between groups; logistic regression models were used to adjust for relevant confounders. P < 0·05 was considered statistically significant. The odds of vitamin A insufficiency/deficiency were 2·17 times higher for non-whites when compared with whites (95 % CI 1·16, 4·05; P = 0·01) after adjustment for relevant confounders. Similarly, the odds of being vitamin E deficient were 3·52 times higher for non-whites (95 % CI 1·51, 8·10; P = 0·003). Those with public health insurance had lower serum lutein concentrations compared with those with private health insurance (P = 0·05), and living in a food desert was associated with lower serum concentrations of β-carotene (P = 0·02), after adjustment for confounders. Subjects with low/marginal food security had higher serum levels of lutein and β-cryptoxanthin compared with those with high food security (P = 0·004 and 0·02 for lutein and β-cryptoxanthin). Diet quality may be a public health concern in economically disadvantaged populations of industrialised societies leading to nutritional disadvantages as well.
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    Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study
    (Public Library of Science, 2018) Liu, Gang; Dhana, Klodian; Furtado, Jeremy; Rood, Jennifer; Zong, Geng; Liang, Liming; Qi, Lu; Bray, George A.; DeJonge, Lilian; Coull, Brent; Grandjean, Philippe; Sun, Qi
    Background: The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Methods and findings In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30–70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6–24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (Ptrend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (Ptrend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (Ptrend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (Ptrend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (Ptrend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight regain period in both men and women. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food packaging and also dense in energy. Conclusions: In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention. Trial registration ClinicalTrials.gov NCT00072995
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    Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease
    (Blackwell Publishing Ltd, 2013) Mendivil, Carlos O.; Rimm, Eric; Furtado, Jeremy; Sacks, Frank
    Background: Low‐density lipoprotein (LDL) with apolipoprotein C‐III (apoC‐III) is the lipoprotein species that most strongly predicts initial and recurring coronary heart disease (CHD) events in several cohorts. Thus, a large portion of the CHD risk conferred by LDL may be attributable to LDL that contains apoC‐III. Very‐low‐density lipoprotein (VLDL) and LDL with apoC‐III have varying amounts of apoE. We hypothesized that a high content of apoE lessens the adverse influence of apoC‐III on the risk of CHD because it promotes the clearance of VLDL and LDL from plasma. Methods and Results: We studied 2 independent cohorts, the Nurses' Health Study, composed of women, and the Health Professionals Follow‐up Study, composed of men. These cohorts contributed to this study 322 women and 418 men initially free of CVD who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow‐up and matched controls who remained free of CHD. The apoE content of LDL with apoC‐III was inversely associated with CHD after multivariable adjustment (relative risk for top versus bottom quintile 0.53, 95% CI 0.35 to 0.80). The apoE content of VLDL with apoC‐III had a similar inverse association with CHD. The highest risks were associated with a high apoB concentration and a low apoE content of LDL with apoC‐III or of VLDL+LDL with apoC‐III. The observed associations were in both male and female cohorts and independent of traditional CHD risk factors and of C‐reactive protein. Conclusions: An increased apoE content in VLDL and LDL with apoC‐III was associated with a lower risk of CHD. Strategies to enrich VLDL and LDL in apoE are worth exploring for the prevention of CHD.
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    ApoC-III and visceral adipose tissue contribute to paradoxically normal triglyceride levels in insulin-resistant African-American women
    (BioMed Central, 2013) Sumner, Anne E; Furtado, Jeremy; Courville, Amber B; Ricks, Madia; Younger-Coleman, Novie; Tulloch-Reid, Marshall K; Sacks, Frank
    Background: African-Americans are more insulin-resistant than whites but have lower triglyceride (TG) concentrations. The metabolic basis for this is unknown. Our goal was to determine in a cross-sectional study the effect of insulin resistance, visceral adipose tissue (VAT) and the apolipoproteins, B, C-III and E, on race differences in TG content of very low density lipoproteins (VLDL). Methods: The participants were 31 women (16 African-American, 15 white) of similar age (37 ± 9 vs. 38 ± 11y (mean ± SD), P = 0.72) and BMI (32.4 ± 7.2 vs. 29.3 ± 6.0 kg/m2, P = 0.21). A standard diet (33% fat, 52% carbohydrate, 15% protein) was given for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. VAT was measured at L2-3. The influence of race, SI, VAT and apolipoproteins on the TG content of VLDL was determined by random effects models (REM). Results: African-Americans were more insulin-resistant (SI: 3.6 ± 1.3 vs. 5.6 ± 2.6 mU/L-1.min-1, P < 0.01) with less VAT (75 ± 59 vs. 102 ± 71 cm2, P < 0.01). TG, apoB and apoC-III content of light and dense VLDL were lower in African-Americans (all P < 0.05 except for apoC-III in light VLDL, P = 0.11). ApoE content did not vary by race. In REM, VAT but not SI influenced the TG concentration of VLDL. In models with race, SI, VAT and all apolipoproteins entered, race was not significant but apoC-III and VAT remained significant determinants of TG concentration in light and dense VLDL. Conclusions: Low concentrations of apoC-III and VAT in African-Americans contribute to race differences in TG concentrations. Trial registration ClinicalTrials.gov Identifier: NCT00484861
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    Racial differences between African-American and white women in insulin resistance and visceral adiposity are associated with differences in apoCIII containing apoAI and apoB lipoproteins
    (BioMed Central, 2014) Wang, Liyun; Sacks, Frank; Furtado, Jeremy; Ricks, Madia; Courville, Amber B; Sumner, Anne E
    Background: African-Americans have higher HDL, less visceral adipose tissue (VAT) and lower triglyceride (TG) and apoCIII concentrations than whites, despite being more insulin-resistant. We studied in African-American and white women the influences of insulin resistance and VAT on the apoAI concentrations of two HDL subspecies, one that contains apoCIII that is associated with increased risk of coronary heart disease (CHD) and one that does not have apoCIII that is associated with decreased CHD; and on the apoCIII concentrations of HDL and of the apoB lipoproteins. Methods: The participants were 32 women (14 African-Americans, 18 white) of similar age (39 ± 12 vs. 42 ± 11y). Mean BMI was 34 kg/m2 in the African-Americans compared to 30 in the whites. A standard diet (33% fat, 52% carbohydrate, 15% protein) was provided for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. Results: After controlling for SI, African-Americans have a higher mean apoAI level in HDL with apoCIII compared with whites (12.9 ± 2.8 and 10.9 ± 2.9 mg/dL, respectively, P = 0.05). SI was associated with higher apoAI in HDL with apoCIII, whereas VAT was not associated with this HDL subspecies. This pattern of results was reversed for apoCIII concentrations in apoB lipoproteins. After adjusting for SI, African-Americans had lower apoCIII in apoB lipoproteins. SI was associated with lower apoCIII in total apoB lipoproteins, whereas VAT was associated with higher apoCIII in all the apoB lipoproteins. Additional adjustment for VAT tended to reduce the difference in apoCIII between the groups. Conclusions: African-American women have a higher HDL with apoCIII level than whites when controlled for insulin sensitivity. African-Americans have lower insulin sensitivity. Insulin sensitivity is associated with higher levels of HDL with apoCIII. ApoCIII levels in VLDL are lower in African-American women than whites, also affected by insulin sensitivity which is associated with low apoCIII in VLDL. VAT has a strong association with apoCIII in apoB lipoproteins but not with apoAI in HDL with apoCIII. Trial registration ClinicalTrials.gov Identifier: NCT00484861
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    Apolipoproteins and their subspecies in human cerebrospinal fluid and plasma
    (Elsevier, 2017) Koch, Manja; Furtado, Jeremy; Falk, Kim; Leypoldt, Frank; Mukamal, Kenneth; Jensen, Majken
    Introduction: Subspecies of apolipoproteins can be defined by fractionating apolipoproteins based on the presence and absence of coexisting apolipoproteins. Methods: We determined age- and sex-adjusted correlations of enzyme-linked immunosorbent assay–measured plasma and cerebrospinal fluid (CSF) apolipoproteins (apoA-I, apoC-III, apoE, and apoJ) or apolipoprotein subspecies (apoA-I with and without apoC-III, ApoE, or apoJ; apoE with and without apoC-III or apoJ) in 22 dementia-free participants. Results: CSF apoE did not correlate with plasma apolipoproteins or their subspecies. CSF apoJ correlated most strongly with plasma apoA-I without apoJ (r = 0.7). CSF apoA-I correlated similarly strong with plasma total apoA-I and all apoA-I subspecies (r ≥ 0.4) except for apoA-I with apoE (r = 0.3) or apoA-I with apoJ (r = 0.3). CSF apoC-III was most strongly correlated with plasma apoA-I with apoC-III (r = 0.7). Discussion CSF levels of some apolipoproteins implicated in the pathophysiology of dementia might be better approximated by specific plasma apolipoprotein subspecies than total plasma concentrations.
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    Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids and tocopherols in HIV-infected Tanzanian women
    (Nature Publishing Group, 2007) Webb, A L; Aboud, S; Furtado, Jeremy; Murrin, C; Campos, Hannia; Fawzi, Wafaie; Villamor, Eduardo
    Background The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women. Objective We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids, and tocopherols during the first year post-partum among 626 HIV-infected Tanzanian women. Design We conducted a randomized, double-blind, placebo controlled trial. Women were assigned to one of four daily oral supplements: vitamin A + β-carotene (VA+BC); multivitamins (B, C, E (MV)); MV+VA+BC; or placebo. Concentrations of breast milk nutrients were determined by HPLC at birth and every 3 mo thereafter. Results Supplementation with VA+BC increased concentrations of retinol, β-carotene, and α-carotene at delivery by 4799, 1791, and 84 nmol/L, respectively, compared to no VA+BC (all p<0.0001). MV supplementation did not increase concentrations of α-tocopherol or δ-tocopherol at delivery but significantly decreased concentrations of breast milk γ-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, α-carotene, and β-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6, and 12 mo compared to no VA+BC. Alpha tocopherol was significantly higher, while γ-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6, and 12 mo post-partum. Conclusions Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission.
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    Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins
    (American Society for Biochemistry & Molecular Biology (ASBMB), 2012) Furtado, Jeremy; Wedel, M. K.; Sacks, Frank
    Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III–containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38–42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III–containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.
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    Metabolism of apolipoprotein A-II containing triglyceride rich ApoB lipoproteins in humans
    (Elsevier BV, 2015) Desai, Nirav; Ooi, Esther M.; Mitchell, Paul; Furtado, Jeremy; Sacks, Frank
    OBJECTIVE: To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo. METHODS: Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II. RESULTS: VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80 ± 0.96 pools/day v.s. 5.09 ± 1.69 pools/day, P = 0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96 ± 8% vs. 45 ± 22%; P = 0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II. CONCLUSION: VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation.
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    Metabolism of Very-Low-Density Lipoprotein and Low-Density Lipoprotein Containing Apolipoprotein C-III and Not Other Small Apolipoproteins
    (Ovid Technologies (Wolters Kluwer Health), 2010-02) Mendivil, Carlos O.; Zheng, Chunyu; Furtado, Jeremy; Lel, Julian; Sacks, Frank
    Objective We aimed to clarify the influence of apolipoprotein C-III (apoCIII) on human apolipoprotein B metabolism. Methods and Results We studied the kinetics of four VLDL, IDL and LDL types containing: (1) OtherApos−CIII−: none of apoCIII, apoAII, apoCI, apoCII or apoE; (2) OtherApos+CIII−: no apoCIII but at least one of the others; (3) OtherApos−CIII+: apoCIII, but not any others; (4) OtherApos+CIII+: apoCIII and at least one other. VLDL and IDL OtherApos−CIII+ and OtherApos−CIII− had similar rates of lipolytic conversion to smaller particles. However, light LDL OtherApos−CIII+ compared to OtherApos−CIII− had much faster conversion to dense LDL, as did light LDL OtherApos+CIII+ compared to OtherApos+CIII−. VLDL and IDL OtherApos−CIII+ had minimal direct removal from circulation, while VLDL and IDL OtherApos+CIII−, rich in apoE, showed fast clearance. Lipoproteins in fraction OtherApos+CIII+ also rich in apoE had very low clearance. Conclusions The results suggest that apoCIII strongly inhibits hepatic uptake of VLDL and IDL overriding the opposite influence of apoE when both are present. The presence of apoCIII on dense VLDL is not associated with slow conversion to IDL, a lipoprotein lipase dependent process; but when on light LDL apoCIII is associated with enhanced conversion to dense LDL, a process involving hepatic lipase.