PMID- 28585214
OWN - NLM
STAT- MEDLINE
DCOM- 20170912
LR  - 20170912
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 960
DP  - 2017
TI  - The Interactions Between Kynurenine, Folate, Methionine and Pteridine Pathways in 
      Obesity.
PG  - 511-527
LID - 10.1007/978-3-319-48382-5_22 [doi]
AB  - Obesity activates both innate and adaptive immune responses in adipose tissue. 
      Elevated levels of eosinophils with depression of monocyte and neutrophil 
      indicate the deficiencies in the immune system of morbidly obese individuals. 
      Actually, adipose tissue macrophages are functional antigen-presenting cells that 
      promote the proliferation of interferon-gamma (IFN-gamma)-producing CD4+ T cells 
      in adipose tissue of obese subjects. Eventually, diet-induced obesity is 
      associated with the loss of tissue homeostasis and development of type 1 
      inflammatory responses in visceral adipose tissue. Activity of inducible 
      indoleamine 2,3-dioxygenase-1 (IDO-1) plays a major role under pro-inflammatory, 
      IFN-gamma dominated settings. One of the two rate-limiting enzymes which can 
      metabolize tryptophan to kynurenine is IDO-1. Tumor necrosis factor-alpha 
      (TNF-alpha) correlates with IDO-1 in adipose compartments. Actually, 
      IDO-1-mediated tryptophan catabolism due to chronic immune activation is the 
      cause of reduced tryptophan plasma levels and be considered as the driving force 
      for food intake in morbidly obese patients. Thus, decrease in plasma tryptophan 
      levels and subsequent reduction in serotonin (5-HT) production provokes satiety 
      dysregulation that leads to increased caloric uptake and obesity. However, after 
      bariatric surgery, weight reduction does not lead to normalization of IDO-1 
      activity. Furthermore, there is a connection between arginine and tryptophan 
      metabolic pathways in the generation of reactive nitrogen intermediates. Hence, 
      abdominal obesity is associated with vascular endothelial dysfunction and reduced 
      nitric oxide (NO) availability. IFN-gamma-induced activation of the inducible 
      nitric oxide synthase (iNOS) and dissociation of endothelial adenosine 
      monophosphate activated protein kinase (AMPK)- phosphoinositide 3-kinase 
      (PI3K)-protein kinase B (Akt)- endothelial NO synthase (eNOS) pathway enhances 
      oxidative stress production secondary to high-fat diet. Thus, reduced endothelial 
      NO availability correlates with the increase in plasma non-esterified fatty acids 
      and triglycerides levels. Additionally, in obese patients, folate-deficiency 
      leads to hyperhomocysteinemia. Folic acid confers protection against 
      hyperhomocysteinemia-induced oxidative stress.
FAU - Engin, Ayse Basak
AU  - Engin AB
AD  - Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, 
      Turkey. abengin@gmail.com.
FAU - Engin, Atilla
AU  - Engin A
AD  - Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, 
      Ankara, Turkey. dr.aengin@gmail.com.
AD  - , Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey. 
      dr.aengin@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Pteridines)
RN  - 343-65-7 (Kynurenine)
RN  - 935E97BOY8 (Folic Acid)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Folic Acid/*metabolism
MH  - Humans
MH  - Inflammation/metabolism/pathology
MH  - Kynurenine/*metabolism
MH  - Methionine/*metabolism
MH  - Obesity/*metabolism/pathology
MH  - Pteridines/*metabolism
MH  - Signal Transduction/*physiology
OTO - NOTNLM
OT  - Dihydrofolate reductase (DHFR)
OT  - Endothelial nitric oxide synthase (eNOS)
OT  - Folate
OT  - Glutathione
OT  - Guanosine triphosphate (GTP)-cyclohydrolase 1 (GTPCH1)
OT  - Hyperhomocysteinemia
OT  - Indoleamine 2,3-dioxygenase-1 (IDO-1)
OT  - Inducible nitric oxide synthase (iNOS)
OT  - Insulin resistance
OT  - Kynurenine
OT  - Neopterin
OT  - Nitric oxide (NO)
OT  - Obesity
OT  - S-adenosylhomocysteine (SAH)
OT  - S-adenosylmethionine (SAM)
OT  - Serotonin (5-hydroxytryptamine, 5-HT)
OT  - Tetrahydrobiopterine (BH4)
OT  - Tetrahydrofolate
OT  - Tryptophan
OT  - Tryptophan 2,3-dioxygenase (TDO2)
OT  - Tumor necrosis factor-alpha (TNF-alpha)
EDAT- 2017/06/07 06:00
MHDA- 2017/09/13 06:00
CRDT- 2017/06/07 06:00
PHST- 2017/06/07 06:00 [entrez]
PHST- 2017/06/07 06:00 [pubmed]
PHST- 2017/09/13 06:00 [medline]
AID - 10.1007/978-3-319-48382-5_22 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2017;960:511-527. doi: 10.1007/978-3-319-48382-5_22.