Markers of inflammation and fat distribution following weight loss in African-American and white women.
ABSTRACT Changes in markers of inflammation (MOI) and fat distribution with weight loss between African-American (AA) and white (W) women have yet to be characterized. The purpose of this study was to examine potential ethnic differences in MOI and regional fat distribution with weight loss, and identify the associations between these markers and changes in regional fat distribution with weight loss among AA and W women. Subjects were 126 healthy, premenopausal women, BMI 27-30 kg/m(2). They were placed on a weight-loss intervention consisting of diet and/or exercise until a BMI <25 was achieved. Fat distribution was measured with computed tomography, and body composition with dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor-α (TNF-α), soluble TNF receptor-I (sTNFR-I), sTNFR-II, C-reactive protein (CRP), and interleukin-6 (IL-6) were assessed. All MOI and adiposity measures significantly decreased with weight loss. Significant ethnic differences with weight loss were observed for fat mass, body fat, intra-abdominal adipose tissue (IAAT), sTNFR-I, and sTNFR-II. Mixed-model analysis indicated that adjusting for change in IAAT explained ethnic differences in change in TNF-α and the decrease in TNF-α with weight loss, while total fat mass only explained the decrease in sTNFR-I and sTNFR-II with weight loss. In conclusion, all MOI decreased following weight loss among W, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed was a greater impact of weight loss on TNF-α in W compared to AA, which was directly associated with IAAT in W.
Full-textDOI: · Available from: Gordon Fisher, Oct 21, 2014
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ABSTRACT: Elevated serum high-sensitivity C-reactive protein (hs-CRP) and low serum 25-hydroxyvitamin D [25(OH)D] are associated with increased cardiovascular disease (CVD) risk. Ethnic differences in serum hs-CRP and 25(OH)D concentrations and CVD are known. to investigate the ethnic differences in hs-CRP concentrations, to assess the influence of 25(OH)D on these ethnic differences and to examine the influence of 25(OH)D on association between hs-CRP and cardiovascular health indices. 62 healthy adults [26 African Americans (AA), 26 European Americans (EA), and 10 Hispanic Americans (HA)], ages 18-55 years. Serum hs-CRP and 25(OH)D as well as pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilatation (FMD) were measured. hs-CRP was inversely associated with 25(OH)D (r = -0.25, P = 0.049), and hs-CRP was positively associated with PWV (r = 0.29, P = 0.04). The association of hs-CRP with PWV attenuated after adjustment for 25(OH)D (P = 0.15). hs-CRP was higher in AA compared to EA (P = 0.05); this differences was reduced by 32% after adjusting for serum 25(OH)D. eventhough the inverse association between serum 25(OH)D and CRP does not infer causality, lower serum 25(OH)D may increase risk for inflammation and endothelial dysfunction. The lower 25(OH)D in AA may predispose to greater inflammation and associated vascular dysfunction.Journal of nutrition and metabolism 09/2012; 2012:475975. DOI:10.1155/2012/475975
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ABSTRACT: Although several epidemiological studies have investigated associations between TNF-α and insulin resistance, results have been inconsistent. We studied the relationship between TNF-α and glucose tolerance status as part of the Insulin Resistance Atherosclerosis Study. Serum concentrations of TNF-α were measured in 1558 individuals in a triethnic population across a spectrum of glucose tolerance. Insulin sensitivity and insulin secretion were assessed by a frequently sampled iv glucose tolerance test (FSIGT). Compared with those with normal glucose tolerance, circulating levels of TNF-α were elevated in individuals with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2D) after adjusting for age, gender, ethnicity, clinic site, and body mass index (3.3, 3.5, and 3.7 pg/ml in subjects with normal glucose tolerance, IGT, and T2D, respectively; P<0.05). Age-, sex-, and body mass index-adjusted levels of TNF-α differed by ethnicity, with Hispanics having the highest levels and African-Americans having the lowest (4.1, 3.6, and 3.0 pg/ml in Hispanics, non-Hispanic whites, and African-Americans, respectively; P<0.05). TNF-α was correlated with waist circumference, high-density lipoprotein, triglycerides, plasminogen activator inhibitor-1 and insulin sensitivity index (SI) (r=0.22, -0.30, 0.35, 0.31, and -0.25; P<0.0001); however, correlations varied by ethnicity. After adjusting for demographics and adiposity, individuals characterized by increased insulin resistance (lower SI), had higher levels of TNF-α than subjects characterized by high insulin sensitivity (3.8 and 3.3 pg/ml in subjects with an SI below/above the median at baseline; P<0.0001). No differences were found for acute insulin response. We confirm that TNF-α is associated with IGT and T2D in a large, multiethnic population, independent of measures of adiposity. Adjusted values of TNF-α, as well as relationships between TNF-α and variables related to T2D, varied by ethnicity. Increased TNF-α levels were predominantly associated with insulin resistance but not with primary defects in β-cell function.The Journal of Clinical Endocrinology and Metabolism 03/2012; 97(3):1032-40. DOI:10.1210/jc.2011-2155 · 6.31 Impact Factor
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ABSTRACT: AIMS/HYPOTHESIS: Successful outcomes have been obtained by exploiting adipose-derived stem cells (ASCs) in regenerative medicine. NADPH oxidase (NOX)-generated reactive oxygen species (ROS) are known to control stem cell self-renewal. Several high glucose (HG)-mediated effects depend on NOX-generated ROS. In this study, we investigated whether, and how mechanistically, HG concentrations control ASC fate in patients with diabetes. METHODS: ASCs from the visceral adipose tissue of non-diabetic (N-ASCs) and diabetic participants (D-ASCs), identified by surface markers, were counted and evaluated for ROS generation and stem cell properties. Their ability to release soluble factors was assessed by BioPlex analysis. To reproduce an in vitro diabetic glucose milieu, N-ASCs were cultured in HG (25 mmol/l) or normal glucose (NG) concentration (5 mmol/l), as control. ASC pluripotency was assessed by in vitro study. The p47(phox) NOX subunit, AKT and octamer-binding transcription factor 4 (OCT4; also known as POU5F1) were knocked down by small-interfering RNA technology. Stem-cell features were evaluated by sphere cluster formation. RESULTS: The ASC number was higher in diabetic patients than in non-diabetic controls. Production of OCT4 and NANOG, stem-cell-specific transcription factors, was upregulated in D-ASCs compared with N-ASCs. Moreover, we found that ROS production and AKT activation drove D-ASC, but not N-ASC, secretion. When N-ASCs were cultured in vitro in the presence of HG, they also expressed OCT4/NANOG and formed spheres. By knock-down of the p47(phox) NOX subunit, AKT and OCT4 we demonstrated that NOX-generated ROS and their downstream signals are crucial for HG-mediated ASC de-differentiation and proinflammatory cytokine production. CONCLUSIONS/INTERPRETATION: We herein provide a rationale for exploiting D-ASCs in regenerative medicine and/or exploiting HG preconditioning to increase ASCs ex vivo.Diabetologia 10/2012; 56(1). DOI:10.1007/s00125-012-2734-7 · 6.88 Impact Factor