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Metabolic syndrome, age‐associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism

Oxenkrug, Gregory F.·2010·Annals of the New York Academy of Sciences
DOI 10.1111/j.1749-6632.2009.05356.x
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Abstract

The neuroendocrine theory of aging identified a cluster of conditions (hypertension, obesity, dyslipidemia, diabetes type 2, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer, e.g., breast and prostate) as age‐associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndromes (MetS). Chronic inflammation is currently considered as a common feature of MetS/AAND. One of the mechanisms by which chronic inflammation might trigger and/or maintain the development of MetS/AAND is transcriptional induction of indoleamine 2,3‐dioxygenase (IDO), rate‐limiting enzyme of tryptophan (TRY)–kynurenine (KYN) pathway, by pro‐inflammatory cytokines (PIC). Activation of IDO shifts TRY metabolism from serotonin synthesis to formation of “kynurenines.” Diminished serotonin production is associated with mental depression while increased formation of kynurenines might contribute to development of MetS/AAND via their apoptotic, neurotoxic, and pro‐oxidative effects, and upregulation of inducible nitric oxide synthase, phospholipase A2, arachidonic acid, prostaglandin, 5‐lipoxygenase, and leukotriene cascade. The combined presence of high producers of alleles of polymorphic PIC genes (e.g., interferon‐gamma and tumor necrosis factor alpha) might account for the genetic predisposition to high levels of PIC production, leading to “superinduction” of IDO. The other rate‐limiting enzyme of the TRY–KYN pathway, TRY 2,3‐dioxygenase, is activated by substrate (TRY) and cortisol. Therefore, KYN–TRY metabolism might be the meeting point for gene‐environment interaction and a new target for prevention and treatment of MetS/AAND.

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Metadata

Authors
Oxenkrug, G. F.
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2010-06
Volume
1199
Issue
1
Pages
1-14
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/j.1749-6632.2009.05356.x
OpenAlex
W1535378236
Cited by
221
References
12
FWCI
4.14
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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CoChat. (2026). Citation check: Metabolic syndrome, age‐associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism. https://app.cochat.ai/papers/10.1111/j.1749-6632.2009.05356.x
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Oxenkrug, G. F. (2010). Metabolic syndrome, age‐associated neuroendocrine disorders, and dysregulation of tryptophan—kynurenine metabolism. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.2009.05356.x

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