BACKGROUND: Increased activity of the immuno-modulatory enzyme indoleamine-2,3-dioxygenase (IDO) during immune activation, results in tryptophan depletion. Tryptophan metabolic changes reduce serotonin production and cause mood disturbances, depression, and impaired satiety, ultimately leading to increased food intake and obesity. Bariatric surgery significantly diminishes immune mediators by substantial weight reduction. We examined IDO-mediated tryptophan-catabolism in morbidly obese patients compared to lean individuals. METHODS: Serum concentrations of kynurenine and tryptophan, calculated kynurenine to tryptophan ratios (kyn trp-1) as an indirect estimate of IDO activity, and neopterin levels reflecting IFN-gamma mediated immune activation, were assessed before and after bariatric surgery. The study population included 22 morbidly obese individuals and 20 normal-weight volunteers. RESULTS: Median weight loss after 24.4+/-5.1 months was 40.6 kg resulting in a reduction of BMI from 44.1 kg/m(2) to 29.9 kg/m(2) (P<0.001). Preoperative kyn trp-1 in morbidly obese patients was significantly increased compared to the control group (41.6+/-20.1 mmol/mol vs 26.5+/-5.1 mmol/mol; P<0.001). Postoperative weight reduction did not lead to normalization of kyn trp-1 (37.9+/-14.0 mmol/mol). As a consequence, tryptophan levels were significantly lower in morbidly obese patients (pre-: 51.5+/-9.2 micromol L(-1) and postoperatively: 46.9+/-7.6 micromol L(-1)) when compared with those of normal-weight controls (64.8+/-9.5 micromol L(-1); P<0.001). In addition, neopterin levels were elevated in the study population pre- and postoperatively compared to normal-weight volunteers (both P<0.001). CONCLUSIONS: Tryptophan depletion in morbidly obese patients is due to chronic immune activation and persists in spite of significant weight reduction following bariatric surgery. This might thereby be responsible for diminished serotonin functions, leading to unchanged satiety dysregulation and a reward-deficiency-syndrome.
BACKGROUND: Increased activity of the immuno-modulatory enzyme indoleamine-2,3-dioxygenase (IDO) during immune activation, results in tryptophan depletion. Tryptophan metabolic changes reduce serotonin production and cause mood disturbances, depression, and impaired satiety, ultimately leading to increased food intake and obesity. Bariatric surgery significantly diminishes immune mediators by substantial weight reduction. We examined IDO-mediated tryptophan-catabolism in morbidly obesepatients compared to lean individuals. METHODS: Serum concentrations of kynurenine and tryptophan, calculated kynurenine to tryptophan ratios (kyn trp-1) as an indirect estimate of IDO activity, and neopterin levels reflecting IFN-gamma mediated immune activation, were assessed before and after bariatric surgery. The study population included 22 morbidly obese individuals and 20 normal-weight volunteers. RESULTS: Median weight loss after 24.4+/-5.1 months was 40.6 kg resulting in a reduction of BMI from 44.1 kg/m(2) to 29.9 kg/m(2) (P<0.001). Preoperative kyn trp-1 in morbidly obesepatients was significantly increased compared to the control group (41.6+/-20.1 mmol/mol vs 26.5+/-5.1 mmol/mol; P<0.001). Postoperative weight reduction did not lead to normalization of kyn trp-1 (37.9+/-14.0 mmol/mol). As a consequence, tryptophan levels were significantly lower in morbidly obesepatients (pre-: 51.5+/-9.2 micromol L(-1) and postoperatively: 46.9+/-7.6 micromol L(-1)) when compared with those of normal-weight controls (64.8+/-9.5 micromol L(-1); P<0.001). In addition, neopterin levels were elevated in the study population pre- and postoperatively compared to normal-weight volunteers (both P<0.001). CONCLUSIONS:Tryptophan depletion in morbidly obesepatients is due to chronic immune activation and persists in spite of significant weight reduction following bariatric surgery. This might thereby be responsible for diminished serotonin functions, leading to unchanged satiety dysregulation and a reward-deficiency-syndrome.
Authors: Giselle G Hamad; Joseph C Helsel; James M Perel; Gina M Kozak; Mary C McShea; Carolyn Hughes; Andrea L Confer; Dorothy K Sit; Carol A McCloskey; Katherine L Wisner Journal: Am J Psychiatry Date: 2012-03 Impact factor: 18.112
Authors: Nitin K Gupta; Ameet I Thaker; Navya Kanuri; Terrence E Riehl; Christopher W Rowley; William F Stenson; Matthew A Ciorba Journal: Inflamm Bowel Dis Date: 2011-08-05 Impact factor: 5.325
Authors: Kenneth Blum; John Bailey; Anthony M Gonzalez; Marlene Oscar-Berman; Yijun Liu; John Giordano; Eric Braverman; Mark Gold Journal: J Genet Syndr Gene Ther Date: 2011-12-23
Authors: Uttam K Raheja; Dietmar Fuchs; Ina Giegling; Lisa A Brenner; Sergio F Rovner; Iqra Mohyuddin; Daniel Weghuber; Harald Mangge; Dan Rujescu; Teodor T Postolache Journal: Pteridines Date: 2015-06 Impact factor: 0.581
Authors: M Pertovaara; A Raitala; M Juonala; T Lehtimäki; H Huhtala; S S Oja; E Jokinen; J S A Viikari; O T Raitakari; M Hurme Journal: Clin Exp Immunol Date: 2007-04 Impact factor: 4.330