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Objectives Identifying sociocultural correlates of neurocognitive dysfunction among Hispanics/Latinos, and their underlying biological pathways, is crucial for understanding disparities in Alzheimer’s disease and related dementias. We examined cross-sectional associations between stress and neurocognition, and the role that metabolic syndrome (MetS) and systemic inflammation might play in these associations. Method Participants included 3,045 adults aged 45–75 (56% female, education 0–20+ years, 86% Spanish-speaking, 23% U.S.-born), enrolled in the Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study. Global neurocognition was the primary outcome and operationalized as the average of the z scores of measures of learning and memory, word fluency, and processing speed. Stress measures included self-report assessments of stress appraisal (perceived and acculturative stress) and exposure to chronic and traumatic stressors. MetS was defined via established criteria including waist circumference, high blood pressure, elevated triglycerides, fasting plasma glucose, and high levels of high-density lipoprotein cholesterol. Systemic inflammation was represented by high-sensitivity C-reactive protein (hs-CRP). Results Separate survey multivariable linear regression models adjusting for covariates showed that higher perceived (b = −0.004, SE = 0.002, p < .05) and acculturative stress (b = −0.004, SE = 0.001, p < .0001) were significantly associated with worse global neurocognition, while lifetime exposure to traumatic stressors was associated with better global neurocognition (b = 0.034, SE = 0.009, p < .001). Neither MetS nor hs-CRP were notable pathways in the association between stress and neurocognition; rather, they were both independently associated with worse neurocognition in models including stress measures (ps < .05). Discussion These cross-sectional analyses suggest that stress appraisal, MetS, and systemic inflammation may be targets to reduce neurocognitive dysfunction among Hispanics/Latinos.

Objectives:We investigated the prospective associations between meat consumption and CVD and whether these relationships differ by dietary quality among African American (AA) adults.Design:Baseline diet was assessed with a regionally specific FFQ. Unprocessed red meat included beef and pork (120 g/serving); processed meat included sausage, luncheon meats and cured meat products (50 g/serving). Incident total CVD, CHD, stroke and heart failure were assessed annually over 9·8 years of follow-up. We characterised dietary quality using a modified Healthy Eating Index-2010 score (m-HEI), excluding meat contributions.Setting:Jackson, MS, USA.Participants:AA adults (n 3242, aged 55 y, 66 % female).Results:Mean total, unprocessed red and processed meat intakes were 5·7 ± 3·5, 2·3 ± 1·8 and 3·3 ± 2·7 servings/week, respectively. Mostly, null associations were observed between meat categories and CVD or subtypes. However, greater intake of unprocessed red meat (three servings/week) was associated with significantly elevated risk of stroke (hazard ratio = 1·43 (CI: 1·07,1·90)). With the exception of a more positive association between unprocessed meat consumption and stroke among individuals in m-HEI Tertile 2, the strength of associations between meat consumption categories and CVD outcomes did not differ by m-HEI tertile. In formal tests, m-HEI did not significantly modify meat–CVD associations.Conclusions:In this cohort of AA adults, total and processed meat were not associated with CVD outcomes, with the exception that unprocessed red meat was related to greater stroke risk. Dietary quality did not modfiy these associations. Research is needed in similar cohorts with longer follow-up and greater meat consumption to replicate these findings.

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56·2 years and proportion female 55·2 %). The National Cancer Institute method was used to estimate dietary intake from two 24-h recalls. We derived DFA patterns using principal component analysis with twenty-six fatty acid and total plant and animal MUFA input variables. Global cognitive function was calculated as the average z-score of four neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake and CVD. DFA patterns were characterised by the consumption of long-chain SFA, animal-based MUFA and trans-fatty acids (factor 1); short to medium-chain SFA (factor 2); very-long-chain n-3 PUFA (factor 3); very-long-chain SFA and plant-based MUFA and PUFA (factor 4). Factor 2 was associated with greater scores for global cognitive function (β = 0·037 (sd 0·012)) and the Digit Symbol Substitution (DSS) (β = 0·56 (sd 0·17)), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (β = 0·23 (sd 0·11)) and B-SEVLT-Recall (β = 0·11 (sd 0·05)) tests (P < 0·05 for all). Factors 1 (β = 0·04 (sd 0·01)) and 4 (β = 0·70 (sd 0·18)) were associated with the DSS test (P < 0·05 for all). The consumption of short to medium-chain SFA may be associated with higher cognitive function among US-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.

OBJECTIVES: To quantify the associations between adherence to U.S. dietary guidelines and inflammation among Bhutanese refugee adults who are eligible to receive SNAP (Supplemental Nutrition Assistance Program) benefits. METHODS: A convenience sample of Bhutanese refugee adults (n = 53, mean age = 47 ± 2 years, 83% female) residing in New Hampshire was recruited. A bilingual community health worker conducted study visits. We estimated diet using the average of three 24-hour recalls. Adherence to U.S. dietary guidelines was defined using the 2015 Healthy Eating Index (HEI), where a higher score indicates greater adherence to guidelines. A fasting blood sample was analyzed for inflammatory biomarkers, IL-6 and TNF-α. The HEI score and score components were expressed in tertiles, and related to biomarkers using ANCOVA. Food rankings were conducted to identify contributors to HEI components. RESULTS: On average, participants lived in the U.S. for 7.8 ± 0.5 years, with a household size of 3.8 ± 0.2 members. The prevalence of overweight/obesity and type 2 diabetes was 82% and 41%, respectively. In multivariate adjusted models, individuals with higher HEI scores had significantly lower IL-6 concentrations (3.1 ± 0.5 pg/mL, 2.5 ± 0.4 pg/mL, and 2.0 ± 0.5 pg/mL by increasing HEI tertile, P-trend = 0.019). In examining the individual HEI components, greater consumption of total fruit (P-trend = 0.02) and whole fruit (P-trend = 0.017) was related to lower IL-6 concentrations, whereas refined grains was associated with higher values (P-trend = 0.036). We observed null associations with TNF-α. The top 5 contributors to fruit consumption were bananas (21.5%), apples (15.5%), mangos (15%), avocados (9.6%), and kiwis (8.8%); those for refined grains included parboiled rice (78.8%), white rice (6.1%), pasta (4.6%), crackers (1.3%), and white bread (1.3%). CONCLUSIONS: In this cross-sectional study of low-income Bhutanese refugee adults, greater adherence to U.S. Dietary Guidelines, particularly for fruit and refined grain consumption, was associated with lower IL-6 concentrations. Over 70% of fruit and 90% of refined grains were represented by only a few foods, which can inform cultural tailoring of SNAP Education interventions in this understudied population. FUNDING SOURCES: The New Hampshire Agricultural Experiment Station.

OBJECTIVE To determine associations of a Mediterranean diet score (MeDS) with 2-year change in cognitive function by type 2 diabetes and glycemic control status and contrast it against other diet quality scores. RESEARCH DESIGN AND METHODS We used data from the longitudinal Boston Puerto Rican Health Study (n = 913; 42.6% with type 2 diabetes at 2 years). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7% [53 mmol/mol]) versus controlled. Two-year change in glycemic control was defined as stable/improved versus poor/declined. We defined MeDS, Healthy Eating Index, Alternate Healthy Eating Index, and Dietary Approaches to Stop Hypertension scores. Adjusted mixed linear models assessed 2-year change in global cognitive function z score, executive and memory function, and nine individual cognitive tests. RESULTS Higher MeDS, but no other diet quality score, was associated with higher 2-year change in global cognitive function in adults with type 2 diabetes (β ± SE = 0.027 ± 0.011; P = 0.016) but not in those without (P = 0.80). Similar results were noted for Mini-Mental State Examination, word recognition, digit span, and clock drawing tests. Results remained consistent for individuals under glycemic control at baseline (0.062 ± 0.020; P = 0.004) and stable/improved over 2 years (0.053 ± 0.019; P = 0.007), but not for individuals with uncontrolled or poor/declined glycemic control. All diet quality scores were associated with higher 2-year memory function in adults without type 2 diabetes. CONCLUSIONS Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.

OBJECTIVES: The literature on n-3 fatty acid (FA) intake and depressive symptoms is inconsistent, potentially due in part to the influence of psychosocial stress. Some evidence supports that n-3 intake may have greater benefit on depressive symptoms among those with high oxidative stress. We quantified the associations between dietary and plasma n-3 FA and 6-y depressive symptoms and measured the modifying effect of psychosocial stress. METHODS: Data are from the Hispanic Community Health Study/Study of Latinos (age 48 y, 63% female). At baseline (2008–11), EPA, DHA and n-3 very-long-chain FAs (n-3VLCFAs) were estimated using two 24-hr recalls and the NCI method. Plasma n-3 FAs were measured by mass spectrometry. Depressive symptoms were measured at baseline and 6-y follow-up with the 10-item Center for Epidemiological Studies Depression Scale (CESD). Approximately 9 months from baseline, the 10-item Perceived Stress (PSS) and Chronic Burden of Stress scales were obtained. Unstratified and psychosocial stress-stratified associations were analyzed using survey linear regression among those with dietary (n = 3537) and plasma (n = 718) FA data. Model covariates included, but were not limited to, baseline CESD score, ethnicity, study site, antidepressant use, total energy intake, and dietary or plasma n-6 FA. RESULTS: Baseline DHA and n-3VLCFA intake were inversely associated with 6-y CESD (P 2 stressors. Plasma n-3 FAs were not associated with CESD in PSS stratified and unstratified analyses. However, plasma n-3 FA were associated with lower CESD score among those with only 2 chronic stressors. CONCLUSIONS: Dietary n-3VLCFAs, but not plasma, were inversely associated with 6-y CESD. Psychosocial stress did not clearly modify these associations. These results provide some evidence that greater n-3VLCFA intake may reduce depressive symptoms among Hispanic/Latino adults. However, considering the limitations of self-reported intake, further research is needed using biomarkers of long-term n-3 consumption and psychosocial stress to confirm our findings. FUNDING SOURCES: None.

OBJECTIVES: Red and processed meat consumption is adversely related to cardiometabolic risk, but the impact of overall dietary quality on this association has not been systematically investigated. We examined the influence of dietary quality on associations of meat intake with biomarkers of cardiometabolic risk. METHODS: Data are from the Jackson Heart Study, a cohort of African Americans (baseline age 55 y, 66% female, 20% diabetes, 9% CVD). We analyzed those with biomarker data available at Visit 1 (2000–04) and at Visit 2 (2005–09) or 3 (2009–13). Diet was assessed by food frequency questionnaire (Visit 1). Total observations used were: Visit 1 (n = 3725), Visit 2 (n = 2736), and Visit 3 (n = 3319). Unprocessed red meat included beef and pork, and processed meat included sausage, lunch, and cured meats. Diet quality was measured by a modified Healthy Eating Index 2010 score (m-HEI) that excluded meat contributions. Modified HEI stratified and unstratified analyses were conducted using linear mixed modeling. Fasting HbA1c and CRP values were log transformed. RESULTS: Meat consumption was not associated with HbA1c in m-HEI stratified or unstratified analyses. A 1 oz/1000 kcal/wk increase in unprocessed red and total meat was associated with a 1.3% ± 0.5% (P = 0.02) and 1.1% ± 0.3% (P = 0.005) higher CRP in unstratified analyses, respectively. Unprocessed red meat was positively associated with CRP in m-HEI tertiles 1 (2.0% ± 0.8%, P = 0.01) and 3 (2.2% ± 0.8%, P = 0.008). Total meat was associated with CRP in m-HEI tertile 1 (2.0% ± 0.6%, P = 0.001) and trended in tertile 3 (1.1% ± 0.6%, P = 0.09); processed meat also approached significance in m-HEI tertile 1 (2.1% ± 1.2%, P = 0.08). There was evidence that m-HEI modified the associations between processed meat and CRP (P-interaction = 0.04), but not for other associations. Excluding those with diabetes or CVD did not alter these results. CONCLUSIONS: Our results do not support that meat intake is associated with HbA1c, or that overall dietary quality modifies these associations. Unprocessed red and total meat intakes were associated with greater CRP in unstratified and subsets of stratified analyses. Associations of processed meat with CRP appeared stronger among those with the poorest diet quality. These data suggest that reduction in red meat intake could benefit inflammation among African American adults. FUNDING SOURCES: The Beef Checkoff.

Background Prior evidence suggests that diet modifies the association of blood ceramides with the risk of incident cardiovascular disease (CVD). It remains unknown if diet quality modifies the association of very long-chain-to-long-chain ceramide ratios with mortality in the community. Objectives Our objectives were to determine how healthy dietary patterns associate with blood ceramide concentrations and to examine if healthy dietary patterns modify associations of ceramide ratios (C22:0/C16:0 and C24:0/C16:0) with all-cause and cause-specific mortality. Methods We examined 2157 participants of the Framingham Offspring Study (mean age = 66 y, 55% women). Blood ceramides were quantified using a validated assay. We evaluated prospective associations of the Dietary Guidelines Adherence Index (DGAI) and Mediterranean-style Diet Score (MDS) with incidence of all-cause and cause-specific mortality using Cox proportional hazards models. Cross-sectional associations of the DGAI and MDS with ceramides were evaluated using multivariable linear regression models. Results The C22:0/C16:0 and C24:0/C16:0 ceramide ratios were inversely associated with all-cause, CVD, and cancer mortality; multivariable-adjusted HRs (95% CIs) were 0.73 (0.67, 0.80) and 0.70 (0.63, 0.77) for all-cause mortality, 0.74 (0.60, 0.90) and 0.69 (0.55, 0.86) for CVD mortality, and 0.75 (0.65, 0.87) and 0.75 (0.64, 0.88) for cancer mortality, respectively. Inverse associations of the C22:0/C16:0 and C24:0/C16:0 ceramide ratios with cancer mortality were attenuated among individuals with a higher diet quality (DGAI or MDS above the median, all P-interaction ≤0.1). The DGAI and MDS had distinct associations with ceramide ratios (DGAI: lower C22:0/C16:0 across quartiles; MDS: higher C24:0/C16:0 across quartiles; all P-trend ≤0.01). Conclusion In our community-based sample, ceramide ratios (C22:0/C16:0 and C24:0/C16:0) were associated with a lower risk of all-cause and cause-specific mortality. Further, we observed that a higher overall diet quality attenuates the association between blood ceramide ratios and cancer mortality and that dietary patterns have distinct relations with ceramide ratios.

BACKGROUND: Minorities, including mainland Puerto Ricans, are impacted disproportionally by Alzheimer’s disease (AD), dementia, and cognitive decline. Studying blood metabolomics in this population has the potential to probe the biological underpinnings of this health disparity. OBJECTIVE: We performed a comprehensive analysis of circulating plasma metabolites in relation to cognitive function in 736 participants from the Boston Puerto Rican Health Study (BPRHS) who underwent untargeted mass-spectrometry based metabolomics analysis and had undergone a battery of in-person cognitive testing at baseline. METHODS: After relevant exclusions, 621 metabolites were examined. We used multivariable regression, adjusted for age, sex, education, apolipoprotein E genotype, smoking, and Mediterranean dietary pattern, to identify metabolites related to global cognitive function in our cohort. LASSO machine learning was used in a complementary analysis to identify metabolites that could discriminate good from poor extremes of cognition. We also conducted sensitivity analyses: restricted to participants without diabetes, and to participants with good adherence to Mediterranean diet. RESULTS: Of 621 metabolites, FDR corrected (p

OBJECTIVES: To characterize nutrient intakes and identify key food sources among Bhutanese refugee adults eligible for SNAP (Supplemental Nutrition Assistance Program) benefits. METHODS: We recruited a convenience sample of Bhutanese refugee adults (n = 54, mean age = 47 y, 83% female) residing in New Hampshire. Diet was estimated from foods recorded using three 24-hr recalls. Selected nutrients included vitamins C, D, E, and K, thiamin, riboflavin, niacin, B6, folate, B12, pantothenic acid, calcium, magnesium, sodium, and saturated fat. Participants were categorized based on meeting the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) of selected nutrients. For sodium and saturated fat, meeting recommendations was defined as consuming

OBJECTIVES: To assess the mediating role of regional brain volume in the relationship between circulating very-long-chain omega-3 fatty acids and global cognitive function. METHODS: Data are from individuals of the Boston Puerto Rican Health Study with a T1-weighted MRI brain scan available approximately 8 y from the baseline visit (n = 200, mean age at baseline = 54.7 y, 77.5% female). Red blood cell fatty acid composition was measured at baseline and very-long-chain omega-3 fatty acid was defined as the sum of EPA and DHA. A battery of 7 cognitive tests was administered at baseline and 8-y follow-up in the language of preference. Global cognitive function was the average z-score of the cognitive tests. Whole MRI brain volumetric measures (of cortical and subcortical grey matter) were quantified using the FreeSurfer processing pipeline. Structural equation modeling was conducted to examine the mediating effect of regional brain volumetric measures on the association between omega-3 fatty acid concentration and global cognitive function. Bivariate associations were assessed by age- and sex-adjusted partial Spearman's rho correlation coefficient with FDR correction. RESULTS: The association between baseline omega-3 fatty acid concentration and 8-y global cognitive function was mediated by several cortical regions including the left caudal middle frontal gyrus, right inferior parietal lobes, and right isthmus of cingulate gyrus. Significant mediators in the subcortex included the putamen, amygdala, left ventral dorsal tract, and right thalamus. Omega-3 fatty acid concentration was positively correlated with global cognitive function (r(s) = 0.17, P

BACKGROUND: Conflicting results on associations between dietary quality and bone have been noted across populations, and this has been understudied in Puerto Ricans, a population at higher risk of osteoporosis than previously appreciated. OBJECTIVE: To compare cross-sectional associations between 3 dietary quality indices [Dietary Approaches to Stop Hypertension (DASH), Alternative Health Eating Index (AHEI-2010), and Mediterranean Diet Score (MeDS)] with bone outcomes. METHOD: Participants (n = 865–896) from the Boston Puerto Rican Osteoporosis Study (BPROS) with complete bone and dietary data were included. Indices were calculated from validated food frequency data. Bone mineral density (BMD) was measured using DXA. Associations between dietary indices (z-scores) and their individual components with BMD and osteoporosis were tested with ANCOVA and logistic regression, respectively, at the lumbar spine and femoral neck, stratified by male, premenopausal women, and postmenopausal women. RESULTS: Participants were 59.9 y ± 7.6 y and mostly female (71%). Among postmenopausal women not taking estrogen, DASH (score: 11–38) was associated with higher trochanter (0.026 ± 0.006 g/cm(2), P

OBJECTIVES: Omega-3 (n-3) fatty acids (FAs) have been shown to have a beneficial effect on stress. As college students experience high levels of stress, our objectives were to quantify the relationship of n-3 FAs and fish consumption with perceived stress (PS) in undergraduate students (age 18–24) at a public New England university. METHODS: Data are from the College Health & Nutrition Assessment Survey, an ongoing cross-sectional study. Data were collected from 2012 - 2017 (68% women, age 18.8 years). Complete data were available on 2477 participants. Diet was assessed by three-day food records; n-3 FA intake was expressed as % of total energy and categorized by quartile. Participants self-reported intake of fish as servings per week over the past 30 days. Fish intake was categorized as

OBJECTIVES: Building evidence suggests that greater adherence to a Mediterranean-style diet (MD) may reduce the risk of cardiovascular disease, type 2 diabetes, and dementia. However, our understanding of the biological mechanisms explaining these associations is limited. Altered sphingolipid metabolism (e.g., increased ceramides, glycosyl- and lactosyl-ceramides, sphingoid bases, and sphingomyelin (SM)) has been implicated in the development of chronic health conditions. We aimed to quantify the impact of MD adherence on circulating patterns of sphingolipid metabolites. METHODS: Cross-sectional analyses were conducted in the Boston Puerto Rican Health Study among those with available data (n = 540, 56 y, 74% women). Diet was obtained with a semi-quantitative FFQ. The MD score (MDS) includes 7 beneficial (e.g., fish, monounsaturated/saturated fat ratio (MUFA/SFA)) and 2 moderation components (e.g., meat and dairy) (range 0–9). Metabolomic analysis was conducted on plasma samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Twenty-six sphingolipids were retained for analyses. Principal components analysis was used to derive 5 sphingolipid patterns. Statistical analyses included multiple linear regression and ANCOVA. RESULTS: Circulating sphingolipid patterns were characterized by dihydro-SMs and SM species with very-long chain fatty acid groups (Factor 1); glycosyl- and lactosyl-ceramides (Factor 2); ceramides (Factor 3); sphingoid bases, sphinganine-1-phosphate and sphingosine-1-phosphate (Factor 4); and SM species with a sphingadienine group (Factor 5). Each 1-point increase in the MDS was associated with lower Factor 3 z-score (β = −0.07 ± 0.03, P = 0.01), as well as with lower Factor 5 z-score (−0.08 ± 0.02, P = 0.001). We observed that individual MDS components including whole grains, fish, and the MUFA/SFA ratio were associated with the sphingolipid patterns (Table 1). CONCLUSIONS: Our results suggest that a Mediterranean-style diet and components of the diet may reduce circulating concentrations of ceramides and certain sphingomyelin species. This may in part explain the protective benefits of this dietary pattern. Longitudinal analyses are needed to clarify the long-term impact of this dietary pattern on sphingolipid metabolism. FUNDING SOURCES: NIH grants P01-AG023394 P50-HL105185 and R01-AG027087. SUPPORTING TABLES, IMAGES AND/OR GRAPHS

The global obesity epidemic has emerged as one of the most important health care problems worldwide. Insulin resistance represents a prevalent pathophysiological abnormality that underlies mechanisms of cardiometabolic disease associated with obesity. Increasing basic, animal, and clinical data support a mechanistic link between insulin resistance and vascular dysfunction, and suggest that improving insulin sensitivity may represent a therapeutic target for combating atherosclerosis and cardiovascular disease. As clinical studies suggest that insulin resistance may play a key role in the cardiovascular benefit achieved with weight loss intervention, we will discuss our clinical perspective and provide evidence that obese individuals with hyperinsulinemia may derive the greatest improvement in vascular function with weight reduction. Lastly, we will address several important unanswered questions in the field that are likely to drive future clinical investigation.

BACKGROUND Synergistic or additive effects or both on cardiometabolic risk may be missed by examining individual fatty acids (FAs). A pattern analysis may be a more useful approach. In addition, it remains unclear whether erythrocyte FA composition relates to insulin resistance among Hispanics/Latinos. OBJECTIVE We derived erythrocyte FA patterns for a Puerto Rican cohort and examined their association with diet and insulin resistance in cross-sectional and prospective analyses. DESIGN At baseline, principal components analysis was used to derive factor patterns with the use of 24 erythrocyte FAs from 1157 participants of the Boston Puerto Rican Health Study (aged 45-75 y). Dietary intake was assessed with a validated semiquantitative food-frequency questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated at baseline and at the 2-y follow-up. Relations between FA patterns and HOMA-IR were analyzed in a sample of 922 participants with available data. RESULTS Five FA patterns were derived, differentiated by 1) relatively high de novo lipogenesis (DNL) FAs and low n-6 (ω-6) FAs, 2) high very-long-chain saturated FAs, 3) high n-3 (ω-3) FAs, 4) high linoleic acid and low arachidonic acid, and 5) high trans FAs. The DNL pattern was positively correlated with sugar and inversely with n-6 and monounsaturated FA intakes. Only the DNL pattern was positively related to baseline HOMA-IR [adjusted geometric means (95% CIs) for quartiles 1 and 4: 1.72 (1.58, 1.87) and 2.20 (2.02, 2.39); P-trend < 0.0001]. Similar associations were observed at 2 y, after adjustment for baseline status [quartiles 1 and 4 means (95% CIs): 1.61 (1.48, 1.76) and 1.84 (1.69, 2.00); P-trend = 0.02]. These results remained consistent after the exclusion of participants with diabetes (n = 485). CONCLUSION Our findings suggest that upregulated DNL associated with a diet high in sugar and relatively low in unsaturated FAs may adversely affect insulin sensitivity in a Hispanic/Latino cohort.

OBJECTIVES: Individual fatty acids (FA) within dietary fat classes [saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and trans FA (TFA)] may differentially affect risk of cognitive impairment. This has received little attention by most previous studies of diet and cognitive function, and few studies are available among Hispanic/Latinos. Our objective was to quantify associations of dietary FA (DFA) patterns with cognitive function among Hispanic/Latinos residing in the US. METHODS: This is a cross-sectional analysis of participants of the Hispanic Community Health Study/Study of Latinos, a diverse cohort recruited from 2008–11 (n = 7842, mean age 55 y, 62% female). Dietary data are from two 24-hr recalls; the National Cancer Institute method was used to estimate usual nutrient intake. Total animal and plant MUFA variables and 26 FA were used to derive DFA patterns by principal components analysis. Global cognitive function was calculated as the average z-score from 3 cognitive tests [Word Fluency (WF), Spanish English Verbal Learning Test (B-SEVLT) sum, and Digit Symbol Substitution (DSS)]. Survey linear regression models, were adjusted for a number of confounders including, but not limited to education, depressive symptoms, ethnicity, study site, physical activity, and total energy. RESULTS: DFA patterns were characterized by greater consumption of long-chain SFA, animal MUFA, and TFA (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain PUFA (Factor 3); very-long-chain SFA, plant MUFA and essential PUFA (Factor 4). Each 1-SD increase in only Factor 2 or 4 was associated with a 0.03 ± 0.01 SD or 0.02 ± 0.01 SD higher global cognitive function score, respectively (P

Polyunsaturated fatty acid (PUFA) consumption is recommended as part of a healthy diet, but evidence of the impact of individual species and biological concentrations on cognitive function is limited. We examined prospective associations of PUFA erythrocyte composition and dietary intake with measures of cognitive function among participants of the Boston Puerto Rican Health Study (aged 57 years). Erythrocyte and dietary PUFA composition were ascertained at baseline and associated with 2-year scores on the Mini-Mental State Exam (MMSE) (n = 1032) and cognitive domain patterns derived from a battery of tests (n = 865), as well as with incidence of cognitive impairment. Erythrocyte and dietary n-3 PUFA were not significantly associated with MMSE score. However, total erythrocyte and dietary n-3 very-long-chain fatty acids (VLCFA), and intake of individual species, were associated with better executive function (P-trend &lt, 0.05, for all). There was evidence that greater erythrocyte n-6 eicosadienoic acid concentration was associated with lower MMSE and executive function scores (P-trend = 0.02). Only erythrocyte arachidonic acid (ARA) concentration predicted cognitive impairment (Odds Ratio = 1.26, P = 0.01). Among Puerto Rican adults, we found that n-3 VLCFA consumption may beneficially impact executive function. Further, these findings provide some evidence that n-6 metabolism favoring greater ARA tissue incorporation, but not necessarily dietary intake, could increase the risk of cognitive impairment.

People with type 2 diabetes (T2D), especially uncontrolled T2D, have high risk of cognitive decline. The role of a Mediterranean diet on cognitive function has not been assessed for adults with vs. without T2D within the same population. We aimed to determine associations of a Mediterranean diet score (MeDS) with 2 year changes in cognitive function by T2D status and by glycemic control status. We used data from the Boston Puerto Rican Health Study (mean (SD) age= 57.2 (7.6) y; n=711 without T2D; n=465 with T2D defined as fasting plasma glucose ≥ 126 mg/dL or medication use). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A1c ≥7%; 74% of T2D sample)) vs. controlled (26%). Two-y changes in glycemic control were defined as stable/improved (32%) vs. poor/declined (68%). Baseline MeDS ranged from 0-9 by scoring participants within the sex-specific healthy median intake of 9 foods and nutrients. The primary outcome was 2 year change in global cognitive function z-score, which included 7 cognitive tests. Adjusting for baseline sociodemographic and lifestyle factors, comorbidities, and baseline measure, MeDS was positively associated with 2 year change in global cognitive function in adults with T2D (β ± SE=0.027 ± 0.011; p=0.016) but not without T2D (-0.002 ± 0.008; p=0.80). Similar results were noted for single cognitive tests (i.e., mini-mental state examination, word recognition, digit span, clock drawing). Better global cognitive function over 2 years with higher MeDS was noted with glycemic control at baseline (0.062 ± 0.020; p=0.004) or stable/improved over 2 years (0.053 ± 0.019; p=0.007), but not for uncontrolled or poor/declined glycemic control. Adhering to a Mediterranean diet is associated with positive 2 year changes in cognitive function among adults with T2D. Glycemic control further sustains these benefits, suggesting that both a healthy Mediterranean diet and effective clinical management may help preserve optimal cognitive function in adults with T2D. Disclosure J. Mattei: None. S.J. Bigornia: None. M. Sotos-Prieto: None. T. Scott: None. X. Gao: None. K.L. Tucker: None.

Background— Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis in fat has been implicated in the development of adipose tissue hypoxia, capillary rarefaction, inflammation, and metabolic dysregulation, but pathophysiological mechanisms remain unknown. In this study, we examined the role of a novel antiangiogenic isoform of vascular endothelial growth factor-A (VEGF-A), VEGF-A 165 b, in human obesity. Methods and Results— We biopsied paired subcutaneous and visceral adipose tissue in 40 obese subjects (body mass index, 45±8 kg/m 2 ; age, 45±11 years) during bariatric surgery and characterized depot-specific adipose tissue angiogenic capacity using an established ex vivo assay. Visceral adipose tissue exhibited significantly blunted angiogenic growth compared with subcutaneous fat ( P 165 b ( P =0.004). The extent of VEGF-A 165 b expression correlated negatively with angiogenic growth ( r =−0.6, P =0.006). Although recombinant VEGF-A 165 b significantly impaired angiogenesis, targeted inhibition of VEGF-A 165 b with neutralizing antibody stimulated fat pad neovascularization and restored VEGF receptor activation. Blood levels of VEGF-A 165 b were significantly higher in obese subjects compared with lean control subjects ( P =0.02), and surgical weight loss induced a marked decline in serumVEGF-A 165 b ( P =0.003). Conclusions— We demonstrate that impaired adipose tissue angiogenesis is associated with overexpression of a novel antiangiogenic factor, VEGF-A 165 b, that may play a pathogenic role in human adiposopathy. Moreover, systemic upregulation of VEGF-A 165 b in circulating blood may have wider-ranging implications beyond the adipose milieu. VEGF-A 165 b may represent a novel area of investigation to gain further understanding of mechanisms that modulate the cardiometabolic consequences of obesity.

ObjectiveTo determine the prospective relationship between changes in sugar-sweetened beverage (SSB) intake and central adiposity in older children.DesignDietary intakes of children were obtained by 3 d food records at ages 10 and 13 years. Waist circumference (WC) and weight and height to determine BMI were measured at 10 and 13 years and total body fat mass (TBFM) at 13 years by dual-energy X-ray absorptiometry. Analyses were conducted using multivariable linear regression. Reporting errors were measured and participants were categorized as under-, plausible and over-reporters of dietary intakes.SettingCommunity-based British cohort of children participating in the Avon Longitudinal Study of Parents and Children.ResultsAmong 2455 older children, increased SSB consumption from ages 10 to 13 years was associated with higher WC (standardized β=0·020, P=0·19), BMI (β=0·028, P=0·03) and TBFM (β=0·017, P=0·20) at 13 years. Effects were strengthened among plausible dietary reporters (n 1059): WC (β=0·097, Pβ=0·074, Pβ=0·065, P=0·003). The association between change in SSB and WC was weakened, but remained statistically significant after accounting for BMI (β=0·042, P=0·02) and TBFM (β=0·048, P=0·01).ConclusionsHigher consumption of SSB from ages 10 to 13 years was associated with a larger WC at age 13 years independent of differences in total adiposity. Accounting for dietary reporting errors strengthened associations. Our findings further support recommendations to limit intakes of SSB to reduce excess weight gain in children and suggest that SSB have an additional deleterious effect on central adiposity.

Background: Multiple diet quality scores have been used to evaluate adherence to specific dietary recommendations or to consumption of healthful foods and nutrients. It remains unknown which score can more strongly predict longitudinal changes in cardiometabolic risk factors.Objective: We aimed to determine associations of 5 diet quality scores [AHA diet score (AHA-DS), Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI)-2005, Mediterranean diet score (MeDS), and Alternative Healthy Eating Index (AHEI)] with 2-y changes in cardiometabolic risk factors in adults 45-75 y old.Methods: Data from the Boston Puerto Rican Health Study were analyzed (n = 1194). Diet quality scores were calculated from a baseline-validated food-frequency questionnaire. Multivariable-adjusted, repeated-subjects, mixed-effects models, adjusted for baseline measures, estimated associations between each z score and 14 individual cardiometabolic factors measured at 2 y.Results: MeDS was significantly associated with lower 2-y waist circumference (β coefficient ± SE: -0.52 ± 0.26, P = 0.048); body mass index (BMI; -0.23 ± 0.08, P = 0.005); log-insulin (-0.06 ± 0.02, P = 0.005); log-homeostasis model assessment of insulin resistance (HOMA-IR; -0.05 ± 0.02, P = 0.030), and log-C-reactive protein (-0.13 ± 0.03, P = 0.0002). Similar but weaker associations were observed for the AHEI with BMI, insulin, and HOMA-IR. The AHA-DS was inversely associated with BMI (-0.17 ± 0.08, P = 0.033). Neither the HEI-2005 nor DASH was significantly associated with any variable. Traditional Puerto Rican foods consumed by individuals with high MeDSs included vegetables and meats in homemade soups, orange juice, oatmeal, beans and legumes, fish, whole milk, corn oil, and beer.Conclusions: The MeDS comprises food components and scores associated with a favorable cardiometabolic profile over 2 y in Puerto Rican adults. An overall healthy diet may be particularly beneficial for maintaining a lower BMI. These results can help identify suitable measures of diet quality in epidemiologic studies and craft meaningful nutritional messages and dietary recommendations for the intended population. This study was registered at clinicaltrials.gov as NCT01231958.

There is scarce information regarding the dietary intake of adults living in Puerto Rico (PR). We aimed to assess intake of nutrients and foods, adherence to recommended intake of nutrients and diet quality, and sociodemographic and lifestyle factors correlated with diet quality among adults in the San Juan metropolitan area of PR. Data were obtained from participants of the cross-sectional convenience-sample Puerto Rico Assessment of Diet, Lifestyle, and Diseases (n = 248, ages 30&ndash, 75 years). Diet quality was defined using the Alternate Healthy Eating Index 2010 (AHEI, range 0&ndash, 110 indicating lower&ndash, higher quality). Linear regression models were used to relate AHEI to sociodemographic and lifestyle factors. Most participants met the Estimated Average Requirement (EAR) for iron, folate, and vitamins B12 and B6, 61% met the EAR for magnesium and 56% for calcium. Only 4% met the EAR for vitamin D, and 7% met the adequate intake for potassium. The main contributors to total energy intake were sugary beverages (11.8%), sweets/desserts (10.2%), dairy (8.5%), mixed dishes (7.6%), starches (6.3%), fast foods (5.5%), and rice (4.9%). The mean (SD) AHEI score was 59.8 (11.0). The lowest AHEI components for which recommended servings were met were red/processed meats, fruit, sodium, sugary beverages, and polyunsaturated fats, and the highest were nuts/legumes, omega-3 fats, and whole grains. Significantly higher AHEI scores were noted for older adults, other ethnicities (vs. Puerto Rican), being single, having some college or higher education, and never/formerly smoking. Adults living in PR report healthy and unhealthy dietary intakes, providing an opportunity to improve diet at the population level.

OBJECTIVES: Evidence suggests that omega-3 fatty acid (n-3 FA) and fish consumption may reduce the risk of the metabolic syndrome (MetS) in older adults. We previously reported that MetS components are prevalent among college students. Identifying modifiable risk factors of developing MetS and its components in young adults will inform potential targets to reduce the risk of age-related health conditions. Our objectives were to measure the cross-sectional impacts of n-3 FA and fish consumption on ≥2 or ≥3 MetS criteria and individual criteria among college students. METHODS: The College Health and Nutrition Assessment Survey is an on-going cross-sectional study at a public New England college. We examined data from Jan 2008 – May 2017. After excluding those with missing data our final sample size was n = 4271 for n-3 FA & n = 2072 for fish intake analyses. Diet was assessed by a 3 day food record; MetS criteria were collected in fasted state. We expressed n-3 FAs as g/1000 kcals/d. Servings of fish/week was obtained via an online survey. Individuals were categorized as consuming ≥ 2 servings/week or not. MetS was defined as meeting ≥ 3 criteria: elevated glucose, triglycerides, blood pressure, waist circumference, and low HDL. Analyses were conducted by logistic regression. RESULTS: The average n-3 FA intake was 0.4 g/1000 kcal/d ± 0.25 & 40% consumed ≥ 2 servings of fish/week. Prevalence estimates for meeting ≥ 2 criteria was 18.8% and 4.8% for MetS. In sex- and energy- adjusted models, n-3 FA consumption was inversely associated with MetS (OR = 0.38; 95%CI: 0.20, 0.71) and ≥2 MetS criteria (OR = 0.67; 95%CI: 0.49, 0.91). Associations were no longer significant after considering additional confounders. Fish consumption was not significantly associated with MetS or ≥2 criteria in any model. Further n-3 FAs and fish consumption was not associated with any individual MetS criteria. CONCLUSIONS: In this cross-sectional study among college students, n-3 FA and fish consumption were not significantly associated with MetS outcomes. Further research is needed in this population using longitudinal study designs to understand long-term impact of n-3 consumption on the development of MetS and associated cardio metabolic risk factors in young adults. FUNDING SOURCES: New Hampshire Agriculture Experiment Station and USDA National Institute of Food and Agriculture Hatch Project 1010738.

Objective: The relationship between central and total fat measured by anthropometry, dual energy X-ray absorptiometry, and magnetic resonance imaging (MRI) with each other and systolic blood pressure (SBP) was examined. Design and Methods: Participants of the Avon Longitudinal Study of Parents and Children were examined at ages 9, 11, 13, and 15 years (n = 3,796-6,567). MRI was available on a subset of children at 11 (n = 156) and 13 (n = 95). Results: Body mass index (BMI) and waist circumference (WC) were highly correlated (r = 0.84-0.91, across ages), and total body fat mass (TBFM) and trunk fat mass (TFM) were very strongly correlated (r ≥ 0.98). Among boys, BMI vs. WC explained a similar degree of variation in TBFM and TFM (41-71% vs. 43-76%, across age and overweight groups); in girls, BMI accounted for 62-73% variance and WC 47-69%. Adiposity measures were generally similarly correlated with SBP within age groups. Further, the relationship between intra-abdominal adipose tissue (IAAT) volume and adiposity measures did not vary greatly at 11 (0.65-0.67) and 13 (0.64-0.67). Conclusions: BMI and WC contain a large amount of overlapping information as evidenced by their high correlation and similarly sized associations with fat mass, SBP, and IAAT. This suggests that WC may be an inadequate marker of central adiposity during childhood.

Accumulation of macrophages and T cells within crown-like structures (CLS) in subcutaneous adipose tissue predicts disease severity in obesity-related insulin resistance (OIR). Although rodent data suggest the B cell is an important feature of these lesions, B cells have not been described within the human CLS. In order to identify B cells in the human subcutaneous CLS (sCLS) in obese subjects and determine whether the presence of B cells predict insulin resistance, we examined archived samples of subcutaneous and omental fat from 32 obese men and women and related findings to clinical parameters. Using immunohistochemistry, we identified B (CD19(+)) and T cells (CD3 (+)) within the sCLS and perivascular space. The presence and density of B cells (B cells per high-power field (pHPF), T cells pHPF, and B cell:T cell (B:T) ratio) were compared with measures of insulin resistance (homeostasis model assessment (HOMA)) and other variables. In 16 of 32 subjects (50%) CD19(+) B cells were localized within sCLS and were relatively more numerous than T cells. HOMA was not different between subjects with CD19(+) vs. CD19(-) sCLS (5.5 vs. 5.3, P = 0.88). After controlling for diabetes and glycemia (hemoglobin A(1c) (HbA(1c))), the B:T ratio correlated with current metformin treatment (r = 0.89, P = 0.001). These results indicate that in human OIR, B cells are an integral component of organized inflammation in subcutaneous fat, and defining their role will lead to a better understanding of OIR pathogenesis and potentially impact treatment.

Objective— The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. Methods and Results— In 30 obese subjects (age 42±11 years, body mass index 46±11 kg/m 2 ) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75–250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot ( P ω -nitro- l -arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. Conclusion— Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.

Inflammation and infiltration of immune cells in white adipose tissue have been implicated in the development of obesity-associated insulin resistance. Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects. In this study, we examined the relationships between AMPK activity, the expression of multiple inflammatory markers in visceral (mesenteric and omental) and abdominal subcutaneous adipose tissue, and whole-body insulin sensitivity in morbidly obese patients (BMI 48 ± 1.9 kg/m2) undergoing gastric bypass surgery. AMPK activity was assessed by western-blots (P-AMPK/T-AMPK) and mRNA levels of various markers of inflammation by qRT-PCR. Patients were stratified as insulin sensitive obese or insulin resistant obese according to their HOMA-IR values. The results indicate that AMPK activity is lower in visceral than in subcutaneous abdominal adipose tissue of these patients and that this is associated with an increased expression of multiple inflammatory genes. They also revealed that AMPK activity is lower in adipose tissue of obese patients who are insulin resistant (HOMA-IR > 2.3) than in BMI-matched insulin sensitive subjects. Furthermore, this difference was evident in all three fat depots. In conclusion, the data suggest that there are close links between reduced AMPK activity and inflammation in white adipose tissue, and whole-body insulin resistance in obese humans. Whether adipose tissue AMPK dysregulation is a causal factor for the development of the inflammation and insulin resistance remains to be determined.

Obesity is associated with increased cardiovascular risk. Although short-term weight loss improves vascular endothelial function, longer term outcomes have not been widely investigated. We examined brachial artery endothelium-dependent vasodilation and metabolic parameters in 29 severely obese subjects who lostor =10% body weight (age 45 +/- 13 years; BMI 48 +/- 9 kg/m(2)) at baseline and after 12 months of dietary and/or surgical intervention. We compared these parameters to 14 obese individuals (age 49 +/- 11 years; BMI 39 +/- 7 kg/m(2)) who failed to lose weight. For the entire group, mean brachial artery flow-mediated dilation (FMD) was impaired at 6.7 +/- 4.1%. Following sustained weight loss, FMD increased significantly from 6.8 +/- 4.2 to 10.0 +/- 4.7%, but remained blunted in patients without weight decline from 6.5 +/- 4.0 to 5.7 +/- 4.1%, P = 0.013 by ANOVA. Endothelium-independent, nitroglycerin-mediated dilation (NMD) was unaltered. BMI fell by 13 +/- 7 kg/m(2) following successful weight intervention and was associated with reduced total and low-density lipoprotein cholesterol, glucose, hemoglobin A(1c), and high-sensitivity C-reactive protein (CRP). Vascular improvement correlated most strongly with glucose levels (r = -0.51, P = 0.002) and was independent of weight change. In this cohort of severely obese subjects, sustained weight loss at 1 year improved vascular function and metabolic parameters. The findings suggest that reversal of endothelial dysfunction and restoration of arterial homeostasis could potentially reduce cardiovascular risk. The results also demonstrate that metabolic changes in association with weight loss are stronger determinants of vascular phenotype than degree of weight reduction.

There are limited data on successful weight management approaches among adolescents from underserved communities. The primary aim of this study was to obtain preliminary data on the efficacy, safety, and acceptability of a lifestyle intervention with milk-based supplements among adolescents from underserved communities. The secondary aims of this study were to assess change in adiposity indices and metabolic indices and to measure compliance. The authors conducted a 12-week open-labeled lifestyle intervention. Adolescents were taught a structured meal plan, including the use of 2 milk-based supplements daily, and participated in weekly lifestyle counseling. Overweight was defined as a body mass index >85th percentile. Percent total body fat was estimated using bioelectric impedance. Fasting blood samples were used to measure insulin indices and other biochemical safety tests. The sample consisted of 40 adolescents (70% girls, 83% minority). Although there was no significant change in body mass index (median [Q1, Q3]; –0.10 [–0.91, 0.61] kg/m2, P = .26), participants showed a decrease in body mass index z score (–0.03 [-0.08, 0.01] SD, P = .01]), weight z score (–0.04 [–0.11, 0.02] SD, P = .001), and percent total body fat (–1.20 [–2.55, –0.12]%, P = .0001). No new onset of type 2 diabetes mellitus was reported, and plasma vitamin D increased ( P –.01). Consumption of milk-based drinks increased from a median of 4.5 to 13.5 servings per week, whereas sugary beverages decreased from 8.0 to 3.8 servings per week. A lifestyle intervention that includes milk-based supplements may safely improve some adiposity indices and decrease intake of sugary beverages among overweight adolescents from underserved areas.

Objective— Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals. Methods and Results— We collected subcutaneous abdominal fat in 77 obese subjects (BMI ≥30 kg/m 2 ) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5±4.5 versus 2.6±1.9, P =0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5±4.4% versus 10.8±3.8%, P Conclusions— In a cohort of obese subjects, we demonstrate that proinflammatory changes in adipose tissue are associated with systemic arterial dysfunction and insulin resistance. These findings suggest that adipose inflammation may be linked to vascular injury and increased cardiovascular risk in obese subjects.

Although excess fat mass is broadly linked to increased cardiovascular risk, the relation between vascular phenotype and degree of obesity in extreme weight categories is unknown. We examined brachial artery vasomotor responses using ultrasound in 203 consecutive patients mainly afflicted with severe obesity (mean age 44 ± 11 yr; body mass index (BMI) 46 ± 9 kg/m2, range 30–72 kg/m2; and body weight 128 ± 29kg, range 69–207 kg). We studied a unique population with >70% of subjects characterized as morbidly obese (BMI ≥ 40) including a 31% group of super-obese individuals (BMI ≥ 50). Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) were examined as measures of endothelium-dependent and -independent dilation, respectively, in relation to clinical, hemodynamic, and metabolic parameters. Endothelial function was significantly impaired in the highest as compared to lowest tertile of body weight (FMD 6.5 ± 4.6 vs. 9.8 ± 4.8%, p

Objective: To evaluate a new scanning electronic microscopic (EM) method for assessing fat cell sizes and compare fat cell size distribution in human adipose tissue from different fat depots before and after weight loss. Research Methods and Procedures: Identical human fat tissue biopsies were separated into two fractions: one used to prepare a fat cell suspension by collagenase digestion followed by photomicrography (collagenase method) and the other fixed in formalin for EM analysis. The EM method was evaluated further by determining fat cell sizes from lean and ob/ob mice. Finally, the EM method was used to assess fat cell sizes in biopsies of different human depots from before and after weight loss. Results: Fat cell size distributions measured by the two methods were not identical, but differences were generally small. The EM method reproduced the well-documented fat cell size difference between lean and ob/ob mice. Large variation was detected in fat cell distributions among three depots in humans. Weight loss reduced fat cell sizes in subjects with large baseline fat cells but had no effect in subjects with small baseline fat cell sizes. Discussion: Our results suggest that the EM method may be a useful alternative for fat cell size analysis of clinical samples.

Background: Omega-3 (n-3) fatty acid (FA) consumption is thought to improve depressive symptoms. However, current evidence is limited, and whether this association exists among Puerto Ricans, a population burdened by depression, remains uncertain. Objectives: We examined the association between omega-3 FA biomarkers and depressive symptoms as well as the potential influence of oxidative stress. Methods: Baseline and longitudinal analyses were conducted in the Boston Puerto Rican Health Study (n = 787; participants aged 57 +/- 0.52 y, 73% women). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration, a measure of oxidative stress, and erythrocyte FA composition were collected at baseline. We calculated the omega-3 index as the sum of eicosapentaenoic and docosahexaenoic acids, expressed as a percentage of total FAs. Baseline and 2-y depressive symptoms were characterized by using the Center for Epidemiological Studies-Depression Scale (CES-D). Statistical analyses included linear and logistic regression. Results: Urinary 8-OHdG concentration tended to modify the relation between the erythrocyte omega-3 index and baseline CES-D score (P-interaction = 0.10). In stratified analyses, the omega-3 index was inversely associated with CES-D score (beta = -1.74, SE = 0.88; P = 0.02) among those in the top quartile of 8-OHdG concentration but not among those in the lower quartiles. The relation between the omega-3 index and CES-D at 2 y was more clearly modified by 8-OHdG concentration (P-interaction = 0.04), where the omega-3 index was inversely associated with CES-D at 2 y, adjusted for baseline (beta = -1.66, SE = 0.66; P = 0.02), only among those with elevated 8-OHdG concentrations. Among individuals not taking antidepressant medications and in the top tertile of urinary 8-OHdG concentration, the omega-3 index was associated with significantly lower odds of a CES-D score >= 16 at baseline (OR: 0.72; 95% CI: 0.53, 0.96) but not at 2 y (OR: 0.83; 95% CI: 0.60, 1.15). Conclusions: An inverse association between the omega-3 index and depressive symptoms was observed among participants with elevated oxidative stress biomarkers. These data suggest that oxidative stress status may identify those who might benefit from omega-3 FA consumption to improve depressive symptoms.

Background Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV). Methods Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area. Results In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05). Conclusions LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation.

BACKGROUND: A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity. OBJECTIVE: To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat. METHODS: We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI⩾30 kg m−2) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS+ or CLS− based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLSs), omental (CLSo) and mesenteric (CLSm) adipose depots. RESULTS: The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS+) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS+ status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved. CONCLUSIONS: In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.

The relationship between central and total fat measured by anthropometry, dual energy X-ray absorptiometry, and magnetic resonance imaging (MRI) with each other and systolic blood pressure (SBP) was examined.Participants of the Avon Longitudinal Study of Parents and Children were examined at ages 9, 11, 13, and 15 years (n = 3,796-6,567). MRI was available on a subset of children at 11 (n = 156) and 13 (n = 95).Body mass index (BMI) and waist circumference (WC) were highly correlated (r = 0.84-0.91, across ages), and total body fat mass (TBFM) and trunk fat mass (TFM) were very strongly correlated (r ≥ 0.98). Among boys, BMI vs. WC explained a similar degree of variation in TBFM and TFM (41-71% vs. 43-76%, across age and overweight groups); in girls, BMI accounted for 62-73% variance and WC 47-69%. Adiposity measures were generally similarly correlated with SBP within age groups. Further, the relationship between intra-abdominal adipose tissue (IAAT) volume and adiposity measures did not vary greatly at 11 (0.65-0.67) and 13 (0.64-0.67).BMI and WC contain a large amount of overlapping information as evidenced by their high correlation and similarly sized associations with fat mass, SBP, and IAAT. This suggests that WC may be an inadequate marker of central adiposity during childhood.

Maladaptive peripheral arterial remodeling, which leads to large arteries with low shear stress, may be associated with increased cardiovascular risk. We tested the hypothesis that arterial enlargement in severe obesity represents maladaptive remodeling and that weight reduction would reverse this process. We evaluated brachial arterial diameter and flow using ultrasound in 244 severely obese patients (age 44 ± 11 years, 80% female, body mass index (BMI) 46 ± 9 kg/m) at baseline and in a group of 67 subjects who experienced weight loss at 1 year. Higher BMI was associated with larger brachial artery diameter ( p = 0.01) and lower shear stress ( p = 0.008), indicating maladaptive remodeling. Significant (≥ 10%) weight reduction was associated with a decrease in resting arterial diameter (—0.19 ± 0.47 mm, p = 0.02) along with a trend toward increased shear stress. Decreased systemic inflammation was associated with weight loss-induced reverse remodeling of the brachial artery. Our findings demonstrate the presence of maladaptive arterial remodeling in advanced obesity that was ameliorated by significant weight loss.

Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site-specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free-fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free-fatty acids (P ≤ 0.01) and negatively correlated to high-density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site-specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI.

Obesity markedly elevates circulating proinflammatory cytokines, which are found to be associated with multiple chronic diseases, such as cardiovascular diseases and type 2 diabetes mellitus. However, the underlying mechanisms for systemic inflammation in obese individuals are poorly understood. One unambiguous physiologic change from lean to obese individuals is a chronic elevation of circulating free fatty acids (FFAs), imparted owing to enlarged fat cell size and population as well as impaired antilipolytic actions of insulin. FFA has been shown to induce cytokine production in several cell types, including macrophages. Obesity is found to be associated with increased macrophage infiltration in adipose tissue, but the cause of such is still not conclusive. On the other hand, adipose tissue is naturally enriched with preadipoctyes. Striking similarity has been documented between preadipocytes and macrophage with even conversion between the two cell types under adequate conditions. Paradoxically, little is known about how FFA affects the function of preadipocytes, the cell type that is closely associated with adipocyte-derived FFA. In this study, we showed that FFA directly activates NF-κB, the master proinflammatory transcription factor and its downstream products IL-6 and TNF-α in clonal preadipocytes (3T3-L1) and in isolated human adipose stromal-vascular cells (SVCs). Inhibition of NF-κB using NF-κB-specific inhibitor (TLCK), proteasome inhibitor (MG132), and siRNA-mediated inhibition of NF-κB-p105 significantly attenuated FFA-stimulated IL-6 production in both 3T3-L1 and human SVAs (p

ObjectivesThe aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status.BackgroundClinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown.MethodsWe prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m2) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels.ResultsPatients age 45 ± 1 years, with BMI 45 ± 9 kg/m2, experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 μIU/ml; n = 99), ≥10% weight loss (compared with

ObjectivesThe purpose of this study was to determine whether obese individuals with reduced adipose tissue inflammation exhibit a more favorable cardiovascular risk profile.BackgroundObesity is associated with a low-grade state of chronic inflammation that might be causally related to cardiometabolic disease.MethodsWith immunohistochemistry, we categorized obese individuals dichotomously as having inflamed fat (n = 78) or noninflamed fat (n = 31) on the basis of the presence (+) or absence (−) of macrophage crown-like structures (CLS) in subcutaneous abdominal fat biopsy samples. We compared their metabolic, vascular, and adipose tissue characteristics with lean subjects (n = 17).ResultsInflamed CLS+ obese individuals displayed higher plasma insulin, homeostasis model assessment, triglycerides, glucose, blood pressure, high-sensitivity C-reactive protein, low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, and brachial artery flow-mediated dilation compared with lean subjects (p < 0.05). Adipose messenger ribonucleic acid expression of inflammatory genes including CD68, leptin, matrix metalloproteinase-9, CD163, and CD8A were significantly greater and vascular endothelial growth factor was lower in the CLS+ group (p < 0.05). In contrast, obese subjects with noninflamed fat exhibited a mixed clinical phenotype with lower insulin resistance, reduced proatherogenic gene expression, and preserved vascular function as in lean subjects. In multiple linear regression adjusting for age and sex, CLS status (beta = −0.28, p = 0.008) and waist circumference (beta = −0.25, p = 0.03) were independent predictors of flow-mediated dilation.ConclusionsThese findings lend support to the novel concept that factors in addition to absolute weight burden, such as qualitative features of adipose tissue, might be important determinants of cardiovascular disease. Therapeutic modulation of the adipose phenotype might represent a target for treatment in obesity.