The Peripheral Kynurenine Pathway and Psychosomatic Comorbidity in Subjects with Morbid Obesity Undergoing Bariatric Surgery

Background: The Kynurenine pathway (KP) is involved in various disorders, but little is known about the KP and psychosomatic complaints. The aim was to study the peripheral KP and psychosomatic comorbidity in subjects with morbid obesity. Methods: Psychosomatic comorbidity (perceived general health, muscle-skeletal pain, well-being, mood disorders, fatigue, self-esteem, sleepiness, and sense of humour) was registered, and serum samples were collected six months before and after bariatric surgery. Results: A total of 141 subjects (men/women, 116/25) with a mean age of 43.0 (SD 8.7) years and BMI of 42.1 (SD 3.8) kg/m2 were included. No significant associations were seen between the psychosomatic disorders and the KP. There was a significant downregulation of all KP metabolites after surgery, a reduction in CRP, and strong associations between CRP and the KP, particularly with the ratios of Kynurenine/Tryptophan and Quinolinic acid (QA)/Xanthurenic acid (XA). The QA/XA ratio was negatively associated with diabetes. Conclusions: The peripheral KP seemed to be of minor importance for the psychosomatic comorbidity in subjects with morbid obesity. The downregulation of all KP metabolites after bariatric surgery indicated reduced inflammation. The QA/XA ratio seemed to be a marker of insulin sensitivity and favourable glucose control.The Peripheral Kynurenine Pathway and Psychosomatic Comorbidity in Subjects with Morbid Obesity Undergoing Bariatric SurgerypublishedVersio

APOE – a genetic marker of comorbidity in subjects with morbid obesity

Background: In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity. Methods: The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Check-list 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles. Results: One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity. Conclusions: The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.acceptedVersio

Changes in circulating sirtuin 1 after bariatric surgery

Background and aims: Obesity is associated with chronic inflammation and oxidative stress. Weight loss after bariatric surgery improves the inflammatory state and risk of cardiovascular disease. Improvement in metabolic dysfunction might be associated with changes in the activity of sirtuin 1 (SIRT1) and we aimed to investigate the effect of bariatric surgery on its circulating levels. Methods and results: This is a sub-study of a prospective cohort study, including 110 subjects with morbid obesity. The surgical procedure was either laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Blood was sampled at inclusion and six and 12 months after surgery. SIRT1 was measured in EDTA plasma with an enzyme-linked immunosorbent assay. The mean age in the population was 43 years, 80% were women and mean body mass index (BMI) was 38.8 kg/m2. RYGB and SG were performed in 89 and 21 subjects, respectively. SIRT1 concentration was significantly reduced from baseline to six and 12 months after surgery, with mean values (SD) 156.8 (82.6), 119.5 (65.6) and 94.9 (45.6) ng/mL, respectively, (p 0.002, all), accompanied by significant reductions in C-reactive protein (CRP), BMI and triglycerides from inclusion (p < 0.001, all). Type of surgery did not differently modify SIRT1 levels (p Z 0.09). CRP and tri glycerides were both positively predictive of SIRT1 levels (p 0.001, both). Conclusion: SIRT1 concentration was significantly lower six and 12 months after bariatric surgery. CRP and triglycerides independently predicted SIRT1 levels, suggesting that reduction in SIRT1 levels might not intrinsically be related to weight reduction, but to improvement in metaflammation.publishedVersio

Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy

The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.publishedVersio

Reply to Paredes et al. Comment on "Aaseth et al. Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients 2022, 14, 2381"

Hereby, we thank Silvia Paredes et al. [...].publishedVersio

APOE Polymorphism and Endocrine Functions in Subjects with Morbid Obesity Undergoing Bariatric Surgery

Background: Obesity is an interplay between genes and the environment, including lifestyle. The genetics of obesity is insufficiently understood. Apolipoprotein E (APOE) genetic polymorphism has been associated with a wide range of disorders. Knowing that some APOE alleles are associated with obesity and endocrine disorders that are common in obesity, the present study aimed at exploring associations between APOE polymorphisms and endocrine functions in subjects with obesity undergoing bariatric surgery. Methods: Analyses of hormones in blood collected before and one year after bariatric surgery were examined. The APOE alleles were grouped as follows: E2 = ε2ε2 + ε2ε3; E3 = ε3ε3 + ε2ε4; E4 = ε3ε4 + ε4ε4. The APOE groups were analysed as nominal and ordered groups (E2-E3-E4) with a linear mixed model to predict the hormonal effects of the groups. Results: Forty-nine women (79%) and thirteen (21%) men with a mean age of 47.7 (SD 8.5) years were included in the study. The adiponectin level was significantly lower (p < 0.05) in the E2 group compared with the E4 group. Adiponectin and cortisol were positively and negatively associated, respectively, with the ordered APOE groups. Conclusions: The ordered APOE groups E2-E3-E4 were significantly associated with high and low levels of adiponectin and cortisol, respectively. The findings indicate APOE-mediated effects on body weight and metabolic functions in subjects with morbid obesity.publishedVersio

The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease

Background: Changes in tryptophan metabolism through the kynurenine pathway (KP) are observed in several disorders and coupled with pathophysiological deviations. Methods: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. Results: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. Conclusions: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.publishedVersio

The effect of ApoE e4 on blood pressure in patients with and without depression

This is an Open Access article licensed under the Creative Commons Attribution License 3.0 (CC BY 3.0) and originally published in Neuropsychiatric Disease and Treatment. You can access the article by following this link: https://dx.doi.org/10.2147/NDT.S106933Dette er en vitenskapelig, fagfellevurdert artikkel som opprinnelig ble publisert i Neuropsychiatric Disease and Treatment. Artikkelen er publisert under lisensen Creative Commons Attribution License 3.0 (CC BY 3.0). Du kan også få tilgang til artikkelen ved å følge denne lenken: https://dx.doi.org/10.2147/NDT.S106933Introduction: Depression is considered an independent risk factor for hypertension, particularly for people with recurrent episodes or a long history of depression. Another risk factor for cardiovascular disease is the Apolipoprotein E e4 allele (ApoE e4). The aim of this study was to examine how ApoE e4 was related to blood pressure (BP) in patients with depression and a control group. Methods: A total of 78 patients, 49 with depression and 29 without, all recruited from the same hospital, underwent ApoE e genotyping (24 had at least one ApoE e4 allele) and examination of BP. Results: In the depression group, but not in the control group, both systolic and diastolic BP were significantly higher in patients with ApoE e4 than in those without. The effect of ApoE e4 on BP differed significantly between the two groups. Conclusion: Our findings showed that the effect of ApoE e4 on BP differed between the patients with depression and the control group. In patients with depression, ApoE e4 was associated with an increase in BP. We suggest that patients with depression and ApoE e4-positive status are particularly prone to develop BP elevation

Do changes in persistent organic pollutants after bariatric surgery cause endocrine disruption?

Background Bariatric surgery results in weight loss, marked endocrine changes and the release of persistent organic pollutants (POPs). The release of POPs might cause endocrine disruption. The study aimed to explore associations between POPs and adiponectin, leptin and ghrelin in subjects undergoing bariatric surgery. Methods: The study included 63 subjects with severe obesity (men/women: 13/50), age (years): 45.0 (8.5), and BMI (kg/m2) 39.1 (3.4). Analyses of adiponectin, leptin and ghrelin and POPs (hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p’-DDE), polychlorinated biphenyl (PCB) 118 (dioxin-like compound; dl), and sum 6 PCB (PCB 28, -52, −101, −138, −153, and −180) were performed before and 12 months after bariatric surgery. Results: There were significant increases in adiponectin and all POPs and a fall in leptin after surgery. The main finding was the highly significant associations between adiponectin and all POPs. The increase in HCB explained 38% of the variation in adiponectin. Conclusions: If the POP-associated increase in adiponectin is a causal effect, the release of POPs might have important clinical consequences. Adiponectin has both positive and negative clinical effects exerted by essentially unknown mechanisms. The effects of released POPs on the metabolic functions in subjects undergoing bariatric surgery deserve further evaluation. © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Do changes in persistent organic pollutants after bariatric surgery cause endocrine disruption?publishedVersio

Patients with depression display cytokine levels in serum and cerebrospinal fluid similar to patients with diffuse neurological symptoms without a defined diagnosis

This is an Open Access article licensed under the Creative Commons Attribution License 3.0 (CC BY 3.0) and originally published in Neuropsychiatric Disease and Treatment. You can access the article by following this link: http://dx.doi.org/10.2147/NDT.S101925Dette er en vitenskapelig, fagfellevurdert artikkel som opprinnelig ble publisert i Neuropsychiatric Disease and Treatment. Artikkelen er publisert under lisensen Creative Commons Attribution License 3.0 (CC BY 3.0). Du kan også få tilgang til artikkelen ved å følge denne lenken: http://dx.doi.org/10.2147/NDT.S101925Introduction: Several reports indicate that inflammation may play a role in depression and demonstrate enhanced systemic levels of inflammatory mediators. We hypothesized that 44 patients with a diagnosis of depression would present with a specific and different serum and cerebrospinal fluid (CSF) cytokine profile compared to 21 patients with diffuse neurological symptoms, of whom 15 had fatigue as a major symptom, but no change in emotional state. Methods: The diagnoses of the patients with depression were according to the International Classification of Diseases, tenth edition (F32–34 spectra). Cytokine profiles in serum and CSF were determined by multiplex analysis, including 27 cytokines, chemokines, and growth factors. Results: No differences could be found between the two groups studied regarding cytokine levels in serum or CSF except for serum interleukin (IL)-1 receptor antagonist that was lower in the depression group. There were only four high correlations (>0.4) between serum and CSF levels of the cytokines, reflecting independent synthesis and turnover in these two compartments. In the control group, fatigue was associated with increased IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor, and interferon-γ (all P<0.01). Conclusion: Patients with depression had a similar cytokine profile as nondepressive patients, both systemically and in CSF. Fatigue was associated with higher levels of some inflammatory markers in the control group. It is possible that the presence of fatigue in a large proportion of patients and controls could contribute to the lack of difference in cytokine levels between these two groups