Elevated GlycA in severe obesity is normalized by bariatric surgery.
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ABSTRACT:
SUBMITTER: Manmadhan A
PROVIDER: S-EPMC6585399 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Elevated GlycA in severe obesity is normalized by bariatric surgery.
Manmadhan Arun A Lin Bing-Xue BX Zhong Judy J Parikh Manish M Berger Jeffrey S JS Fisher Edward A EA Heffron Sean P SP
Diabetes, obesity & metabolism 20180828 1
Chronic inflammation drives many obesity-associated conditions including atherosclerosis. GlycA, a marker of systemic inflammation with lower intra-individual variability than high sensitivity C-reactive protein, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of body weight loss on GlycA is untested. Obese (body mass index [BMI] 44.6 ± 6.6 kg/m<sup>2</sup> ), ...[more]
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Project description:OBJECTIVES:Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes. DESIGN:Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included. RESULTS:Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients. CONCLUSIONS:We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome-host interactions in severe obesity. TRIAL REGISTRATION NUMBER:NCT01454232.
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Project description:IntroductionObesity is associated with low-grade systemic inflammation. The "inflammome" is a network layout of the inflammatory pattern. The systemic inflammome of obesity has not been described as yet. We hypothesized that it can be significantly worsened by smoking and other comorbidities frequently associated with obesity, and ameliorated by bariatric surgery (BS). Besides, whether or not these changes are mirrored in the lungs is unknown, but obesity is often associated with pulmonary inflammation and bronchial hyperresponsiveness.ObjectivesWe sought to: (1) describe the systemic inflammome of morbid obesity; (2) investigate the effects of sex, smoking, sleep apnea syndrome, metabolic syndrome and BS upon this systemic inflammome; and, (3) determine their interplay with pulmonary inflammation.MethodsWe studied 129 morbidly obese patients (96 females; age 46 ± 12 years; body mass index [BMI], 46 ± 6 kg/m2) before and one year after BS, and 20 healthy, never-smokers, (43 ± 7 years), with normal BMI and spirometry.ResultsBefore BS, compared with controls, all obese subjects displayed a strong and coordinated (inflammome) systemic inflammatory response (adiponectin, C-reactive protein, interleukin (IL)-8, IL-10, leptin, soluble tumor necrosis factor-receptor 1(sTNF-R1), and 8-isoprostane). This inflammome was not modified by sex, smoking, or coexistence of obstructive sleep apnea and/or metabolic syndrome. By contrast, it was significantly ameliorated, albeit not completely abolished, after BS. Finally, obese subjects had evidence of pulmonary inflammation (exhaled condensate) that also decreased after BS.ConclusionsThe systemic inflammome of morbid obesity is independent of sex, smoking status and/or comorbidities, it is significantly reduced by BS and mirrored in the lungs.
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| S-EPMC6067110 | biostudies-literature
Project description:ImportanceThe variability and durability of improvements in pain and physical function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) are not well described.ObjectivesTo report changes in pain and physical function in the first 3 years following bariatric surgery, and to identify factors associated with improvement.Design, setting, and participantsThe Longitudinal Assessment of Bariatric Surgery-2 is an observational cohort study at 10 US hospitals. Adults with severe obesity undergoing bariatric surgery were recruited between February 2005 and February 2009. Research assessments were conducted prior to surgery and annually thereafter. Three-year follow-up through October 2012 is reported.ExposuresBariatric surgery as clinical care.Main outcomes and measuresPrimary outcomes were clinically meaningful presurgery to postsurgery improvements in pain and function using scores from the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (ie, improvement of ≥5 points on the norm-based score [range, 0-100]) and 400-meter walk time (ie, improvement of ≥24 seconds) using established thresholds. The secondary outcome was clinically meaningful improvement using the Western Ontario McMaster Osteoarthritis Index (ie, improvement of ≥9.7 pain points and ≥9.3 function points on the transformed score [range, 0-100]).ResultsOf 2458 participants, 2221 completed baseline and follow-up assessments (1743 [78.5%] were women; median age was 47 years; median body mass index [BMI] was 45.9; 70.4% underwent RYGB; 25.0% underwent LAGB). At year 1, clinically meaningful improvements were shown in 57.6% (95% CI, 55.3%-59.9%) of participants for bodily pain, 76.5% (95% CI, 74.6%-78.5%) for physical function, and 59.5% (95% CI, 56.4%-62.7%) for walk time. Additionally, among participants with severe knee or disability (633), or hip pain or disability (500) at baseline, approximately three-fourths experienced joint-specific improvements in knee pain (77.1% [95% CI, 73.5%-80.7%]) and in hip function (79.2% [95% CI, 75.3%-83.1%]). Between year 1 and year 3, rates of improvement significantly decreased to 48.6% (95% CI, 46.0%-51.1%) for bodily pain and to 70.2% (95% CI, 67.8%-72.5%) for physical function, but improvement rates for walk time, knee and hip pain, and knee and hip function did not (P for all ≥.05). Younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms were associated with presurgery-to-postsurgery improvements in multiple outcomes at years 1, 2, and 3.Conclusions and relevanceAmong a cohort of participants with severe obesity undergoing bariatric surgery, a large percentage experienced improvement, compared with baseline, in pain, physical function, and walk time over 3 years, but the percentage with improvement in pain and physical function decreased between year 1 and year 3.Trial registrationclinicaltrials.gov Identifier: NCT00465829.
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Project description:Inflammation, oxidative stress and dysregulation of adipokines are thought to be pathophysiological mechanisms linking obesity to the development of insulin resistance and atherosclerosis. In adults, bariatric surgery reduces inflammation and oxidative stress, and beneficially changes the levels of several adipokines, but little is known about the postsurgical changes among adolescents.In two separate longitudinal cohorts we evaluated change from baseline of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemo-attractant protein-1 (MCP-1), oxidized low-density lipoprotein cholesterol (oxLDL), adiponectin, leptin and resistin up to 12 months following elective laparoscopic Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) surgery in adolescents with severe obesity.In cohort 1, which consisted of 39 adolescents (mean age 16.5±1.6 years; 29 females) undergoing either RYGB or VSG, IL-6 (baseline: 2.3±3.4 pg ml(-1) vs 12 months: 0.8±0.6 pg ml(-1), P<0.01), leptin (baseline: 178±224 ng ml(-1) vs 12 months: 41.4±31.9 ng ml(-1), P<0.001) and oxLDL (baseline: 41.6±11.6 U l(-1) vs 12 months: 35.5±11.1 U l(-1), P=0.001) significantly decreased and adiponectin significantly increased (baseline: 5.4±2.4 μg ml(-1) vs 12 months: 13.5±8.9 μg ml(-1), P<0.001). In cohort 2, which consisted of 13 adolescents (mean age 16.5±1.6 years; 10 females) undergoing RYGB, results were similar: IL-6 (baseline: 1.7±0.9 pg ml(-1) vs 12 months: 0.4±0.9 pg ml(-1), P<0.05) and leptin (baseline: 92.9±31.3 ng ml(-1) vs 12 months: 37.3±33.4 ng ml(-1), P<0.001) significantly decreased and adiponectin significantly increased (baseline: 6.1±2.9 μg ml(-1) vs 12 months: 15.4±8.0 μg ml(-1), P<0.001). When the cohorts were combined to evaluate changes at 12 months, oxLDL also significantly decreased (baseline: 39.8±16.7 U l(-1) vs 12 months: 32.7±11.9 U l(-1), P=0.03).Bariatric surgery produced robust improvements in markers of inflammation, oxidative stress and several adipokines among adolescents with severe obesity, suggesting potential reductions in risk for type 2 diabetes and cardiovascular disease.
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Project description:Projection of gut microbiome pre and post bariatric surgery to predict surgery outcome
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Project description:Bariatric surgery Targeted loci environmental
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