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Adverse effects of long-term weight gain on microvascular endothelial function.

ABSTRACT: BACKGROUND:Endothelial dysfunction is the first stage of the atherosclerotic cascade, and independently associated with cardiovascular events. We evaluated the associations of longitudinal changes in weight, waist circumference, body fat percentage and lean mass index with changes in endothelial function. METHODS:521 community-based subjects who belonged to hypertensive sibships and had no history of myocardial infarction or stroke had their anthropometric measures and endothelial function assessed a mean of 8.5 years apart. Endothelial function was assessed with brachial artery ultrasound, yielding measures of flow-mediated dilation and reactive hyperemia. We used multivariable linear regression with generalised estimating equations to assess the associations of longitudinal changes (?) in anthropometric measures with ? flow-mediated dilation and reactive hyperemia, adjusting for potential confounders. RESULTS:Mean±standard deviation age was 57.6±8.7years, 58% were women, and 72% were hypertensive. Most (84%) were overweight or obese at baseline. At end of follow-up, flow-mediated dilation and reactive hyperemia increased by 1.9±7.6% and 51.2±605.8% on average, respectively. In multivariable linear regression, changes in anthropometric measures were not associated with changes in flow-mediated dilation. However, ? weight (?±SE: -9.00±2.35), ? waist circumference (-6.78±2.21) and ? body fat percentage (-19.72±5.62, P<0.0001 for each) were inversely associated with ? reactive hyperemia. ? lean mass index was not associated with ? reactive hyperemia. CONCLUSIONS:Long-term increases in weight, waist circumference and body fat percentage are associated with progressive worsening of microvascular endothelial function, but not conduit vessel endothelial function, in subjects without a history of cardiovascular events, independently of risk factors.

SUBMITTER: Coutinho T

PROVIDER: S-EPMC6146400 | biostudies-literature | 2018 Sep - Oct

REPOSITORIES: biostudies-literature

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Adverse effects of long-term weight gain on microvascular endothelial function.

Coutinho Thais T Turner Stephen T ST Kullo Iftikhar J IJ

Obesity research & clinical practice 20180628 5

<h4>Background</h4>Endothelial dysfunction is the first stage of the atherosclerotic cascade, and independently associated with cardiovascular events. We evaluated the associations of longitudinal changes in weight, waist circumference, body fat percentage and lean mass index with changes in endothelial function.<h4>Methods</h4>521 community-based subjects who belonged to hypertensive sibships and had no history of myocardial infarction or stroke had their anthropometric measures and endothelial ...[more]

PMID: 30224028

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Project description:BACKGROUND:Phthalates are known endocrine disruptors and peroxisome proliferator-activated receptor (PPAR) activators, potentially capable of promoting an obesogenic effect. Pregnant women are especially vulnerable to phthalate exposure due to physiological and metabolic changes during pregnancy, including those related to the metabolism of xenobiotics. Phthalate exposure during pregnancy has been associated with early gestational weight gain, however, its effect on long-term weight gain remains unclear. The aim of the present study was to evaluate the association between phthalate exposure during pregnancy and long-term changes in weight among women. METHODS:Urinary phthalate concentrations, socioeconomic, anthropometry and information on diet and socioeconomic status were collected during pregnancy from 178 women from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. Maternal body weight and diet information was also collected up to 5 times in the first year postpartum and twice during follow-up visits 5.2-10.7 years later. A path analysis was performed to assess associations between urinary phthalate metabolite levels during pregnancy and change in weight (kg) per year after delivery, including age, education, living with/without partner, parity, daily energy intake and breastfeeding duration. RESULTS:The mean age at pregnancy was 27.3?±?5.9 years and mean body mass index during the first postpartum year was 27.07?±?4.22?kg/m2. On average, women gained 3.48?kg (0.52?±?0.84?kg/year). A unit increase in log-transformed mono-3-carboxypropyl phthalate (MCPP) was associated with 0.33?kg (95% CI: 0.09, 0.56) higher weight gain per year, and mono-benzyl phthalate (MBzP) with 0.21?kg (95% CI: -0.38, -0.03) lower weight gain per year. CONCLUSION:Exposure to certain phthalates during pregnancy may be associated with long-term weight change in women. More studies on the effects of phthalate exposure during pregnancy on women's long-term health are required.

Project description:BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.

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Adverse effects of long-term weight gain on microvascular endothelial function.

Publications

Adverse effects of long-term weight gain on microvascular endothelial function.

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