Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes

Mudry, Jonathan M.; Alm, Petter S.; Erhardt, Sophie; Goiny, Michel; Fritz, Tomas; Caidahl, Kenneth; Zierath, Juleen R.; Krook, Anna; Wallberg-Henriksson, Harriet

doi:10.1002/dmrr.2798

Cited by 46 publications

(54 citation statements)

References 18 publications

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“…Indeed in our study, TNF mRNA was actually reduced in HFD‐fed mice. The only upregulated enzyme downstream in this pathway in HFD‐fed mice intestine was KMO, which may be consistent with an increased KMO in omental adipose tissue from obese women and higher kynurenine levels positively correlate with body mass index . In our studies, DIO mice had no change in intestinal mucosal tph1 expression, whereas in obese subjects TPH1 (Figure , Pathway 2) expression was increased in jejunum .…”

Section: Discussionsupporting

confidence: 85%

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Jennis

Cavanaugh

Leo

et al. 2017

Neurogastroenterology Motil

122

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Section: Discussionsupporting

confidence: 85%

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Jennis

Cavanaugh

Leo

et al. 2017

Neurogastroenterology Motil

122

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“…Diabetic retinopathy patients have elevated serum Kyn [72]. mRNA expression of KAT I and KAT II is modestly reduced in skeletal muscle from type 2 diabetic patients compared with that in normal glucose tolerant humans [73]. Exercise enhances KAT activity [73] may through upregulation of skeletal muscle KATs mediated by PGC-1α1 [22].…”

Section: Abnormal Kp and Risk Factors For Cvdmentioning

confidence: 99%

“…mRNA expression of KAT I and KAT II is modestly reduced in skeletal muscle from type 2 diabetic patients compared with that in normal glucose tolerant humans [73]. Exercise enhances KAT activity [73] may through upregulation of skeletal muscle KATs mediated by PGC-1α1 [22]. As expected, bariatric surgery is associated with the improvement and even the remission of T2D.…”

Section: Abnormal Kp and Risk Factors For Cvdmentioning

confidence: 99%

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Song

Ramprasath

Wang

et al. 2017

Cell. Mol. Life Sci.

172

134

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Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Following this first step, the KP has two major branches, one branch is mediated by kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU) and is responsible for the formation of 3-HK, 3-HAA, and quinolinic acid (QA); and another branch is controlled by kynurenine aminotransferase (KAT), which generates KA. Uncontrolled Trp catabolism has been demonstrated in distinct CVD, thus, understanding the underlying mechanisms by which regulates KP enzyme expression and activity is paramount. This review highlights the recent advances on the effect of KP enzyme expression and activity in different tissues on the pathological mechanisms of specific CVD, KP is an inflammatory sensor and modulator in the cardiovascular system, and KP catabolites act as the potential biomarkers for CVD initiation and progression. Moreover, the biochemical features of critical KP enzymes and principles of enzyme inhibitor development are briefly summarized, as well as the therapeutic potential of KP-enzyme inhibitors against CVD is briefly discussed.

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“…Most recently, Mudry et al reported a decline in kynurenine after exercise in humans, 28 suggesting that exercise-induced kynurenine degradation may be one of the reasons for lower kynurenine in those with higher muscle strength and functional capacity. In contrast, in most previous studies, inflammatory processes were regarded as the principal pathophysiological mechanism in patients with activated kynurenine pathway.…”

Section: Potential Mechanismsmentioning

confidence: 99%

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure　― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―

Konishi

Ebner

Springer

et al. 2017

Circ J

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Background: Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/ function plays a pathophysiological role. Methods and Results:Plasma kynurenine was assessed in 249 patients with HF (67±11 years, 21% women) and in 45 controls from the SICA-HF study. Kynurenine was higher in 173 HF patients with reduced ejection fraction (EF) and in 76 patients with preserved EF than controls (3.5±1.5, 3.4±1.3, and 2.4±1.1 μmol/L, P<0.001). In HF patients, kynurenine had an inverse association with handgrip strength (r=-0.26, P<0.01), peak oxygen consumption (r=-0.29, P<0.01), 6-min walk distance (r=-0.23, P<0.01), and had a positive association with kidney and liver function parameters. No correlation was observed between kynurenine and lean mass. On multivariable linear regression analysis, a significant association was noted between kynurenine and peak oxygen consumption even after adjustment for age, gender, BMI, and hemoglobin (β=-0.23, P<0.001). Patients with higher kynurenine were at higher risk of death (adjusted HR, 1.46 per 1 μmol/L, P<0.01). Conclusions:In stable HF patients, plasma kynurenine was inversely correlated with muscle strength and functional capacity as well as with liver and kidney function.

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Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes

Cited by 46 publications

References 18 publications

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure　― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―

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Direct effects of exercise on kynurenine metabolism in people with normal glucose tolerance or type 2 diabetes

Cited by 46 publications

References 18 publications

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Microbiota‐derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure ― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―

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Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure　― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―