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Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery.

ABSTRACT: Obesity is associated with increased inflammation and insulin resistance. In conditions with chronic immune activation, low plasma vitamin B6-levels are described, as well as an increased kynurenine:tryptophan-ratio (KTR). We investigated circulating tryptophan, kynurenine and its metabolites, neopterin, B-vitamins, CRP, and HbA1c in individuals with obesity before and after bariatric surgery.This longitudinal study included 37 patients with severe obesity, scheduled for bariatric surgery. Blood samples were taken at inclusion and at three months and one year postoperatively.We observed significant positive correlations between HbA1c and both 3-hydroxy-kynurenine and 3-hydroxyanthranilic acid at inclusion. After surgery, fasting glucose, HbA1C and triglycerides decreased, whereas HDL-cholesterol increased. Tryptophan, kynurenine and its metabolites, except for anthranilic acid, decreased during weight loss. The KTR and CRP decreased while vitamin B6 increased during the year following operation, indicating reduced inflammation (all p<0.05).In patients with obesity subjected to bariatric surgery, levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid seemed to be positively correlated to impaired glucose tolerance. One year following surgery, plasma levels of the kynurenine metabolites were substantially decreased, along with a metabolic improvement. The relation of circulating kynurenine pathway metabolites with biomarkers of metabolic impairment in patients with obesity needs further evaluation.

SUBMITTER: Christensen MHE

PROVIDER: S-EPMC5798786 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery.

Christensen Monika H E MHE Fadnes Dag J DJ Røst Therese H TH Pedersen Eva R ER Andersen John R JR Våge Villy V Ulvik Arve A Midttun Øivind Ø Ueland Per M PM Nygård Ottar K OK Mellgren Gunnar G

PloS one 20180205 2

<h4>Objective</h4>Obesity is associated with increased inflammation and insulin resistance. In conditions with chronic immune activation, low plasma vitamin B6-levels are described, as well as an increased kynurenine:tryptophan-ratio (KTR). We investigated circulating tryptophan, kynurenine and its metabolites, neopterin, B-vitamins, CRP, and HbA1c in individuals with obesity before and after bariatric surgery.<h4>Methods</h4>This longitudinal study included 37 patients with severe obesity, sche ...[more]

PMID: 29401505

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Project description:Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA's metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6-12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA's acute and chronic insults.

Dataset Information

Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery.

Publications

Inflammatory markers, the tryptophan-kynurenine pathway, and vitamin B status after bariatric surgery.

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