Dataset Information

Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

ABSTRACT: Context:Obesity is associated with subclinical white adipose tissue inflammation, as defined by the presence of crown-like structures (CLSs) consisting of dead or dying adipocytes encircled by macrophages. In humans, bariatric surgery-induced weight loss leads to a decrease in CLSs, but the effects of rapid diet-induced weight loss on CLSs and metabolism are unclear. Objective:To determine the effects of rapid very-low-calorie diet-induced weight loss on CLS density, systemic biomarkers of inflammation, and metabolism in obese postmenopausal women. Design:Prospective cohort study. Setting:Rockefeller University Hospital, New York, NY. Participants:Ten obese, postmenopausal women with a mean age of 60.6 years (standard deviation, ±3.6 years). Main Outcome Measures:Effects on CLS density and gene expression in abdominal subcutaneous adipose tissue, cardiometabolic risk factors, white blood count, circulating metabolites, and oxidative stress (urinary isoprostane-M) were measured. Results:Obese subjects lost approximately 10% body weight over a mean of 46 days. CLS density increased in subcutaneous adipose tissue without an associated increase in proinflammatory gene expression. Weight loss was accompanied by decreased fasting blood levels of high-sensitivity C-reactive protein, glucose, lactate, and kynurenine, and increased circulating levels of free fatty acids, glycerol, ?-hydroxybutyrate, and 25 hydroxyvitamin D. Levels of urinary isoprostane-M declined. Conclusion:Rapid weight loss stimulated lipolysis and an increase in CLS density in subcutaneous adipose tissue in association with changes in levels of circulating metabolites, and improved systemic biomarkers of inflammation and insulin resistance. The observed change in levels of metabolites (i.e., lactate, ?-hydroxybutyrate, 25 hydroxyvitamin D) may contribute to the anti-inflammatory effect of rapid weight loss.

SUBMITTER: Aleman JO

PROVIDER: S-EPMC5686624 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

Alemán José O JO Iyengar Neil M NM Walker Jeanne M JM Milne Ginger L GL Da Rosa Joel Correa JC Liang Yupu Y Giri Dilip D DD Zhou Xi Kathy XK Pollak Michael N MN Hudis Clifford A CA Breslow Jan L JL Holt Peter R PR Dannenberg Andrew J AJ

Journal of the Endocrine Society 20170425 6

<h4>Context</h4>Obesity is associated with subclinical white adipose tissue inflammation, as defined by the presence of crown-like structures (CLSs) consisting of dead or dying adipocytes encircled by macrophages. In humans, bariatric surgery-induced weight loss leads to a decrease in CLSs, but the effects of rapid diet-induced weight loss on CLSs and metabolism are unclear.<h4>Objective</h4>To determine the effects of rapid very-low-calorie diet-induced weight loss on CLS density, systemic biom ...[more]

PMID: 29264516

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Project description:BACKGROUND:Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. METHODS:We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by 1H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. RESULTS:Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-?-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. CONCLUSIONS:VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome. Trial Registration ClinicalTrials.gov NCT01699906, 4-Oct-2012, Retrospectively registered. URL- https://clinicaltrials.gov/ct2/show/NCT01699906.

Project description:Little is known about the effect of intentional weight loss and subsequent weight regain on cardiometabolic risk factors in older adults. The objective of this study was to determine how cardiometabolic risk factors change in the year following significant intentional weight loss in postmenopausal women, and if observed changes were affected by weight and fat regain.Eighty, overweight and obese, older women (age = 58.8±5.1 years) were followed through a 5-month weight loss intervention and a subsequent 12-month nonintervention period. Body weight/composition and cardiometabolic risk factors (blood pressure; total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; fasting glucose and insulin; and Homeostatic Model Assessment of Insulin Resistance) were analyzed at baseline, immediately postintervention, and 6- and 12-months postintervention.Average weight loss during the 5-month intervention was 11.4±4.1kg and 31.4% of lost weight was regained during the 12-month follow-up. On average, all risk factor variables were significantly improved with weight loss but regressed toward baseline values during the year subsequent to weight loss. Increases in total cholesterol, triglycerides, glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance during the postintervention follow-up were significantly (p < .05) associated with weight and fat mass regain. Among women who regained weight, model-adjusted total cholesterol (205.8±4.0 vs 199.7±2.9mg/dL), low-density lipoprotein cholesterol (128.4±3.4 vs 122.7±2.4mg/dL), insulin (12.6±0.7 vs 11.4±0.7mg/dL), and Homeostatic Model Assessment of Insulin Resistance (55.8±3.5 vs 50.9±3.7mg/dL) were higher at follow-up compared with baseline.For postmenopausal women, even partial weight regain following intentional weight loss is associated with increased cardiometabolic risk. Conversely, maintenance of or continued weight loss is associated with sustained improvement in the cardiometabolic profile.

Project description:Changes in sex hormones with weight loss might have implications for breast cancer prevention but have not been examined extensively, particularly in African-American (AA) women.We conducted a prospective study of 278 overweight/obese postmenopausal women (38% AA) not taking hormone therapy within the Weight Loss Maintenance Trial. All participants lost at least 4 kg after a 6-month weight-loss phase and attempted to maintain weight loss during the subsequent 12 months. We evaluated the percentage changes in estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) using generalized estimating equations.In all study phases, AA women had higher levels of estrogen and testosterone concentrations, independent of adiposity. On average, participants lost 7.7 kg during the weight-loss phase, and concentrations of estrone (-5.7%, P = 0.006), estradiol (-9.9%, P <0.001), free estradiol (-13.4%, P <0.0001), and free testosterone (-9.9%, P <0.0001) decreased, while the SHBG concentration (16.2%, P <0.001) increased. Weight change did not significantly affect total testosterone or other androgen concentrations. Compared with non-AA women, AA women experienced less change in estrogens per kilogram of weight change (that is, per 1 kg weight loss: estrone, -0.6% vs. -1.2%, P-interaction = 0.10; estradiol, -1.1% vs. -1.9%, P-interaction = 0.04; SHBG, 0.9% vs. 1.6%, P-interaction = 0.006; free estradiol, -1.4% vs. -2.1%, P-interaction = 0.01).To the best of our knowledge this is the first study to examine and compare the effects of intentional weight loss and maintenance on a panel of sex hormones in AA women and non-AA women. Although speculative, these data suggest hormonal differences may contribute to different racial patterns of breast cancer incidence and mortality and encourage further investigations to understand the long-term effects of weight loss on sex hormones in obese postmenopausal women.ClinicalTrials.gov: NCT00054925.

Project description:To examine the relationships between plasma and tissue markers of systemic and vascular inflammation and obesity and insulin resistance and determine the effects of aerobic exercise training plus weight loss (AEX+WL) and weight loss (WL) alone on these biomarkers.Prospective controlled study.Veterans Affairs Medical Center and University research setting.Overweight and obese sedentary postmenopausal women (N = 77).Six months, 3 d/wk AEX+WL (n = 37) or WL (n = 40).Total-body dual-energy X-ray absorptiometry, abdominal computed tomography, hyperinsulinemic-euglycemic clamps (a criterion standard method of assessing insulin sensitivity), adipose tissue biopsies (n = 28), and blood for homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA).Body weight (P < .001), percentage of fat (P < .001), visceral fat (P < .005), triglyceride levels (P < .001), and systolic blood pressure decreased comparably after WL and AEX+WL (P = .04). Maximal oxygen consumption increased 16% after AEX+WL (P < .001). Insulin resistance decreased in both groups (P = .005). Glucose utilization according to the clamp increased 10% (P = .04) with AEX+WL and 8% with WL (P = .07). AEX+WL decreased CRP by 29% (P < .001) and WL by 21% (P = .02). SAA levels decreased twice as much after AEX+WL (-19%, P = .02) as after WL (-9%, P = .08). Plasma sICAM-1 and sVCAM-1 levels did not change, but women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose (P = .02), insulin (P = .02), and insulin resistance (P = .004). Gluteal ICAM messenger ribonucleic acid levels decreased 27% after AEX+WL (P = .02) and did not change after WL.Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP, SAA, and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women.

Dataset Information

Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

Publications

Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

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