title: Inflammatory, endocrine and metabolic correlates of fatigue in obese children.
abstract: Alterations in endocrine functions and low-grade systemic inflammation represent fundamental characteristics of obesity. These biological systems have been repeatedly linked to fatigue symptoms. The aim of the study was to assess the relationship between fatigue dimensions and metabolic/inflammatory markers in a sample of non-diabetic obese children. The possibility that inflammation-induced alterations in tryptophan metabolism relates to specific dimensions of fatigue was also investigated in a subsample of patients. The study was conducted in 41 obese children, median aged 12 [9-15] years, recruited in a pediatric tertiary center. Three dimensions of fatigue (e.g., general fatigue, sleep/rest, cognitive fatigue) were assessed using the Pediatric Quality of Life Inventory Multidimentional Fatigue Scale. In addition, a principal component analysis was performed to identify fatigue dimensions that were specific to the population under study. This analysis extracted five relevant dimensions corresponding respectively to concentration, energy, self-perceived cognitive efficiency, sleep/rest and motivation/anhedonia. Blood samples were collected for the measurement of inflammatory and metabolic markers, including high sensitivity C-reactive protein (hs-CRP), insulin, uricemia and glycaemia. Tryptophan, kynurenine and neopterin levels were also determined in a subsample of 17 patients. In the whole population under study, cognitive fatigue and reduced motivation/anhedonia were associated with BMI, independently of sex and age. The dimension of reduced motivation/anhedonia was associated with insulin resistance and inflammatory biomarkers. The association with insulin resistance persisted when the extent of fat mass (BMI-SDS) was taken into account. No association was found between tryptophan metabolism and specific dimensions of fatigue, but kynurenine and the kynurenine/tryptophan ratio correlated with insulin and HOMA-IR. These data indicate that insulin resistance in non diabetic obese children is associated with both cognitive fatigue and reduced motivation/anhedonia and with alterations in tryptophan metabolism. Further investigations are needed to determine whether inflammation-induced alterations in tryptophan metabolism is directly or indirectly implicated in insulin resistance and related fatigue.
authors.affiliation: CHU Bordeaux, Centre Spécialise Obésité, Hopital des Enfants, F-33076 Bordeaux, France; Univ Bordeaux, Nutrition and Integrative Neurobiology, F-33076 Bordeaux, France. Electronic address: pascal.barat@chu-bordeaux.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Barat
authors.affiliation: CHU Bordeaux, Centre Spécialise Obésité, Hopital des Enfants, F-33076 Bordeaux, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Meiffred
authors.affiliation: Univ Bordeaux, Nutrition and Integrative Neurobiology, F-33076 Bordeaux, France; CHU Bordeaux, Nuclear Medecine, F-33604 Pessac, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Brossaud
authors.affiliation: Division of Biological Chemistry, Biocenter Innsbruck Medical University Center for Chemistry and Biomedicine, A-6020 Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Univ Bordeaux, Nutrition and Integrative Neurobiology, F-33076 Bordeaux, France; CHU Bordeaux, Nuclear Medecine, F-33604 Pessac, France.
authors.forename: Jean-Benoit
authors.initials: JB
authors.lastname: Corcuff
authors.affiliation: CHU Bordeaux, Centre Spécialise Obésité, Hopital des Enfants, F-33076 Bordeaux, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Thibault
authors.affiliation: Univ Bordeaux, Nutrition and Integrative Neurobiology, F-33076 Bordeaux, France; INRA, Nutrition and Integrative Neurobiology, F-33076 Bordeaux, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Capuron
mesh_terms: D000293:Adolescent; D059445:Anhedonia / Q000502:physiology*; D057565:Apathy / Q000502:physiology*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism*; D002648:Child; D005221:Fatigue / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D007737:Kynurenine / Q000097:blood*; D008297:Male; D005222:Mental Fatigue / Q000097:blood / Q000503:physiopathology; D063766:Pediatric Obesity / Q000097:blood*; D014364:Tryptophan / Q000097:blood*
chemical_list: D007328:Insulin; D007737:Kynurenine; D014364:Tryptophan; D002097:C-Reactive Protein
keywords: Children; Fatigue; Indoleamine-2,3-dioxygenase (IDO-1); Inflammation; Insulin resistance; Obesity