The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium

Abstract Background The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. Methods We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m2) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. Results Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m2, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10−6, r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). Conclusion Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.

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Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03182-1 ◽

2021 ◽

Author(s):

Susanna M. Wallerstedt ◽

Karin Nylén ◽

Magnus A. B. Axelsson

Keyword(s):

Bariatric Surgery ◽

Antiepileptic Drugs ◽

Therapeutic Drug ◽

Serum Concentrations ◽

Consistent Finding ◽

Low Calorie ◽

Post Surgery ◽

Low Calorie Diet ◽

Calorie Diet ◽

The Impact

Abstract Purpose As a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations. Methods In a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered. Results In all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6–17 individuals, 11 substances: 1–4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: −0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself. Conclusions Serum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

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Effectiveness, Compliance, and Acceptability of Preoperative Weight Loss with a Liquid Very Low-Calorie Diet Before Bariatric Surgery in Real Practice

Obesity Surgery ◽

10.1007/s11695-018-3444-0 ◽

2018 ◽

Vol 29 (1) ◽

pp. 54-60 ◽

Cited By ~ 3

Author(s):

Kamthorn Yolsuriyanwong ◽

Komdej Thanavachirasin ◽

Kimberly Sasso ◽

Lauren Zuro ◽

Jessica Bartfield ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Preoperative Weight Loss ◽

Very Low Calorie Diet ◽

Low Calorie ◽

Low Calorie Diet ◽

Calorie Diet ◽

Preoperative Weight ◽

Real Practice

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Efficacy of a dietitian‐led very low calorie diet (VLCD) based model of care to facilitate weight loss for obese patients prior to elective, non‐bariatric surgery

Journal of Human Nutrition and Dietetics ◽

10.1111/jhn.12819 ◽

2020 ◽

Cited By ~ 1

Author(s):

S. B. Griffin ◽

L. J. Ross ◽

M. J. Burstow ◽

B. Desbrow ◽

M. A. Palmer

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Obese Patients ◽

Model Of Care ◽

Very Low Calorie Diet ◽

Low Calorie ◽

Low Calorie Diet ◽

Calorie Diet

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Very low-calorie diet in candidates for bariatric surgery: change in body composition during rapid weight loss

Clinics ◽

10.6061/clinics/2019/e560 ◽

2019 ◽

Vol 74 ◽

Cited By ~ 3

Author(s):

Marcela Pires Serafim ◽

Marco Aurelio Santo ◽

Alexandre Vieira Gadducci ◽

Veruska Magalhães Scabim ◽

Ivan Cecconello ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Body Composition ◽

Rapid Weight Loss ◽

Very Low Calorie Diet ◽

Low Calorie ◽

Low Calorie Diet ◽

Calorie Diet

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Effectiveness of a Low-Calorie Diet for Liver Volume Reduction Prior to Bariatric Surgery: a Systematic Review

Obesity Surgery ◽

10.1007/s11695-020-05070-6 ◽

2020 ◽

Author(s):

Marleen M. Romeijn ◽

Aniek M. Kolen ◽

Daniëlle D. B. Holthuijsen ◽

Loes Janssen ◽

Goof Schep ◽

...

Keyword(s):

Systematic Review ◽

Bariatric Surgery ◽

Weight Loss ◽

Liver Volume ◽

Volume Reduction ◽

Restricted Diet ◽

Low Calorie ◽

Low Calorie Diet ◽

Calorie Diet ◽

Very Low Calorie Diets

Abstract An energy-restricted diet is often prescribed before bariatric surgery to reduce weight and liver volume. While very-low-calorie diets (VLCDs, 450–800 kcal per day) have shown to be effective, the effectiveness of low-calorie diets (LCDs, 800–1500 kcal per day) is less obvious. The objective of this systematic review was to elucidate the effectiveness of LCD on liver volume reduction in patients awaiting bariatric surgery. Eight studies (n = 251) were included describing nine different diets (800–1200 kcal, 2–8 weeks). An LCD was effective in liver volume reduction (12–27%) and weight loss (4–17%), particularly during the first weeks. The LCD showed an acceptable patients’ compliance. Based on these findings, an LCD (800–1200 kcal), instead of a VLCD, for 2 to 4 weeks should be preferred.

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Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis

Acta Endocrinologica ◽

10.1530/eje-12-0955 ◽

2013 ◽

Vol 168 (6) ◽

pp. 829-843 ◽

Cited By ~ 197

Author(s):

Giovanni Corona ◽

Giulia Rastrelli ◽

Matteo Monami ◽

Farid Saad ◽

Michaela Luconi ◽

...

Keyword(s):

Systematic Review ◽

Bariatric Surgery ◽

Weight Loss ◽

Body Weight ◽

Meta Analysis ◽

Body Weight Loss ◽

Low Calorie ◽

Testosterone Levels ◽

Low Calorie Diet ◽

Calorie Diet

ObjectiveFew randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels.DesignMeta-analysis.MethodsAn extensive Medline search was performed including the following words: ‘testosterone’, ‘diet’, ‘weight loss’, ‘bariatric surgery’, and ‘males’. The search was restricted to data from January 1, 1969 up to August 31, 2012.ResultsOut of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51–10.95) vs 2.87 (1.68–4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029).ConclusionsThese data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.

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Extensive weight loss can reduce immune age by altering IgG N-glycosylation

10.1101/2020.04.24.20077867 ◽

2020 ◽

Author(s):

Valentina L Greto ◽

Ana Cvetko ◽

Tamara Štambuk ◽

Niall J Dempster ◽

Domagoj Kifer ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Biological Age ◽

List Type ◽

Low Calorie ◽

Inflammatory Conditions ◽

Low Calorie Diet ◽

Calorie Diet ◽

One Year

ABSTRACTBackgroundObesity represents a global health threat, and is associated not only with exponentially increased cardiometabolic morbidity and mortality, but with adverse clinical outcomes in patients infected with SARS-CoV-2 as well. Enzymatic attachment of complex oligosaccharides to proteins (glycosylation) is highly responsive to numerous (patho)physiological conditions and ageing, which is perhaps best exemplified on IgG. The prospect of immune age reduction, by reverting induced glycosylation changes through metabolic intervention, opens many possibilities. Herein, we have investigated whether weight loss interventions affect inflammation- and ageing-related glycosylation alterations, in a longitudinal cohort of bariatric-surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal TwinsUK cohort.MethodsIgG and plasma N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet and then to bariatric surgery, across multiple timepoints. Similarly, plasma glycome was analysed in 1,680 TwinsUK participants and longitudinally monitored during a 20-year follow-up.FindingsLow-calorie diet induced marked increase in low branched and significant decrease in highly branched, more complex plasma N-glycans – the change opposite to the one typically observed in inflammatory conditions. Bariatric surgery resulted in extensive, gradual alterations in IgG glycome, that accompanied progressive weight loss during one year follow-up. We observed significant increase in digalactosylated and sialylated, and substantial decrease in agalactosylated and core fucosylated IgG glycans. In general, such IgG glycan profile is associated with a younger biological age and reflects enhanced anti-inflammatory IgG potential. The TwinsUK cohort replicated weight loss-associated agalactosylation decrease and digalactosylation increase, estimated through BMI decrease over a 20-year-period.InterpretationAltogether, these findings highlight that weight loss substantially affects both plasma and IgG N-glycosylation, resulting in improved biological and immune age.GRAPHICAL ABSTRACTHIGHLIGHTSObesity is associated to circulating pro-inflammatory high branched N-glycans and IgG agalactosylationHigh branching of N-glycans from total plasma proteins decreases after 3-week low-calorie dietIgG galactosylation and sialylation increase after bariatric surgery-induced weight lossDecrease of BMI over time is associated to increased IgG galactosylation and a reduction of biological age

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Extensive weight loss reduces glycan age by altering IgG N-glycosylation

International Journal of Obesity ◽

10.1038/s41366-021-00816-3 ◽

2021 ◽

Author(s):

Valentina L. Greto ◽

Ana Cvetko ◽

Tamara Štambuk ◽

Niall J. Dempster ◽

Domagoj Kifer ◽

...

Keyword(s):

Bariatric Surgery ◽

Weight Loss ◽

Protein Glycosylation ◽

Biological Age ◽

Low Calorie ◽

Inflammatory Conditions ◽

Low Calorie Diet ◽

Calorie Diet ◽

Value Range ◽

Weight Loss Interventions

Abstract Background Obesity, a major global health problem, is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to inflammation and ageing. The prospect of biological age reduction, by changing glycosylation patterns through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. Methods IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1680 participants from the TwinsUK cohort. Results Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG N-glycome that accompanied progressive weight loss during 1-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG N-glycans (adjusted p value range 7.38 × 10−04–3.94 × 10−02). This IgG N-glycan profile is known to be associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease (adjusted p value 1.79 × 10−02) and an increase in digalactosylation (adjusted p value 5.85 × 10−06). Conclusions Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced glycan and biological age.

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