Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 5;13(2):e0192169.
doi: 10.1371/journal.pone.0192169. eCollection 2018.

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

Monika H E Christensen  1   2 , Dag J Fadnes  3 , Therese H Røst  1 , Eva R Pedersen  1   4 , John R Andersen  5   6 , Villy Våge  6   7 , Arve Ulvik  8 , Øivind Midttun  8 , Per M Ueland  1   9 , Ottar K Nygård  4   10 , Gunnar Mellgren  10   11
Affiliations

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

Monika H E Christensen et al. PLoS One. .

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: Updated Competing Interest statement: The affiliation with Bevital does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. The kynurenine pathway of tryptophan metabolism.
IDO, indoleamine 2,3-dioxygenase; TDO, tryptophan 2,3-dioxygenase; KAT, kynurenine aminotransaminase; KMO, kynurenine 3-monooxygenase; KYNU, kynureninase; 3OH-kynurenine, 3-hydroxy kynurenine; 3OH-anthranilic acid, 3-hydroxy anthranilic acid; B6, vitamin B6 (pyridoxal 5`-phosphate); B2, vitamin B2 (flavin adenine dinucleotide).
Fig 2
Fig 2. Correlations of fasting glucose, HbA1c and the triglyceride:HDL ratio with tryoptophan, kynurenine and the kynurenine metabolites, inflammatory markers, vitamin B6 and vitamin B3 at baseline.
Regression coefficient based on Spearman rank correlation test, corrected for age, gender and eGFR, are shown in the figure. Tg, triglyceride; HDL, high density lipoprotein; Trp, tryptophan; Kyn, kynurenine; KA kynurenic acid; AA, anthranilic acid; HK, 3-hydroxy kynurenine; XA, xanthurenic acid; HAA, 3-hydroxy anthranilic acid; QA, quinolinic acid; KTR, kynurenine:tryptophan ratio; PLP, pyridoxal 5`-phosphate. *p-value < 0.05; **p-value < 0.005.
Fig 3
Fig 3. Inflammatory markers after bariatric surgery.
Samples were measured at baseline, 3 months and after one year in 37 patients undergoing bariatric surgery. P values for trend over time are estimated with a random intercept mixed model, adjusted for type of operation and vitamin B supplementation. Data are given as median (25th to 27th percentile).
See this image and copyright information in PMC

References

    1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377(9765):557–67. Epub 2011/02/08. doi: 10.1016/S0140-6736(10)62037-5 . - DOI - PMC - PubMed
    1. Prospective Studies C, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083–96. Epub 2009/03/21. doi: 10.1016/S0140-6736(09)60318-4 ; PubMed Central PMCID: PMC2662372. - DOI - PMC - PubMed
    1. Sjostrom L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden A, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014;311(22):2297–304. Epub 2014/06/11. doi: 10.1001/jama.2014.5988 . - DOI - PubMed
    1. Gloy VL, Briel M, Bhatt DL, Kashyap SR, Schauer PR, Mingrone G, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ. 2013;347:f5934 Epub 2013/10/24. doi: 10.1136/bmj.f5934 ; PubMed Central PMCID: PMC3806364. - DOI - PMC - PubMed
    1. Grant RW, Stephens JM. Fat in flames: Influence of cytokines and pattern recognition receptors on adipocyte lipolysis. Am J Physiol Endocrinol Metab. 2015:ajpendo 00053 2015. Epub 2015/06/11. doi: 10.1152/ajpendo.00053.2015 . - DOI - PubMed

Publication types