Chronic immune activation underlies morbid obesity: is IDO a key player?
Morbid obesity is associated with low-grade systemic inflammation and immune activation. Thereby various pro-inflammatory cytokines like TNF-alpha, IL-1, IL-6, IFN-gamma and hormones, such as leptin are synthesized and released in human adipose tissue. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is widely distributed in mammals and is inducible preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine which, depending on cell type and enzymatic repertoires, is subsequently converted to finally form niacin. More recently, it has been proposed that activation of IDO is also critically involved in the regulation of immune responses. In obesity plasma tryptophan concentrations have been shown to be decreased and to be independent of weight reduction or dietary intake. In addition, we previously demonstrated that IDO mediated tryptophan catabolism due to chronic immune activation is the cause for such reduced tryptophan plasma levels in morbidly obese patients compared to lean individuals. Furthermore, these tryptophan metabolic changes may subsequently reduce serotonin production and cause mood disturbances, depression, and impaired satiety ultimately leading to increased caloric uptake and obesity. IDO-mediated tryptophan degradation due to chronic immune activation can therefore be considered as the driving force for food intake. We here review the potential pathogenic links between chronic immune activation and decreased IDO mediated tryptophan and serotonin levels in morbid obesity.
Brandacher
G
G
Department of General and Transplant Surgery, D. Swarovski Research Laboratory, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
Hoeller
E
E
Fuchs
D
D
Weiss
Helmut G
HG
D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000818:Animals; D050110:Bariatric Surgery; D054439:Ghrelin; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D009767:Obesity, Morbid / Q000276:immunology* / Q000378:metabolism / Q000601:surgery; D036361:Peptide Hormones / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism; D015431:Weight Loss
D054439:Ghrelin; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020738:Leptin; D036361:Peptide Hormones; D012701:Serotonin; D014364:Tryptophan