Browsing by Subject "INDOLE-3-PROPIONIC ACID"

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  • Puurunen, Jenni; Sulkama, Sini; Tiira, Katriina; Araujo, Cesar; Lehtonen, Marko; Hanhineva, Kati; Lohi, Hannes (2016)
    Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent and multifactorial neuropsychiatric disorder in the human population worldwide. Complex etiology and clinical heterogeneity have challenged the research, diagnostics and treatment of the disease. Hyperactive and impulsive behaviour has also been observed in dogs, and they could offer a physiologically relevant model for human ADHD. As a part of our ongoing study to understand the molecular etiology of canine anxiety traits, this study was aimed to pilot an approach to identify metabolic biomarkers in canine ADHD-like behaviours for research, diagnostics and treatment purposes. Methods: We collected fresh plasma samples from 22 German Shepherds with varying ADHD-like behaviours. All dogs were on the same controlled diet for 2 weeks prior to sampling. A liquid chromatography combined with mass spectrometry (LC-MS)-based non-targeted metabolite profiling was performed to identify plasma metabolites correlating with the ADHD-like behaviour of the dogs. Results: 649 molecular features correlated with ADHD-like behavioural scores (p(raw) <0.05), and three of them [sn-1 LysoPC(18: 3), PC(18: 3/18: 2) and sn-1 LysoPE(18: 2)] had significant correlations also after FDR correction (pFDR <0.05). Phospholipids were found to negatively correlate with ADHD-like behavioural scores, whereas tryptophan metabolites 3-indolepropionic acid (IPA) and kynurenic acid (KYNA) had negative and positive correlations with ADHD-like behavioural scores, respectively. Conclusions: Our study identified associations between canine ADHD-like behaviours and metabolites that are involved in lipid and tryptophan metabolisms. The identified metabolites share similarity with earlier findings in human and rodent ADHD models. However, a larger replication study is warranted to validate the discoveries prior to further studies to understand the biological role of the identified metabolites in canine ADHD-like behaviours.
  • de Mello, Vanessa D.; Paananen, Jussi; Lindstrom, Jaana; Lankinen, Maria A.; Shi, Lin; Kuusisto, Johanna; Pihlajamaki, Jussi; Auriola, Seppo; Lehtonen, Marko; Rolandsson, Olov; Bergdahl, Ingvar A.; Nordin, Elise; Ilanne-Parikka, Pirjo; Keinanen-Kiukaanniemi, Sirkka; Landberg, Rikard; Eriksson, Johan G.; Tuomilehto, Jaakko; Hanhineva, Kati; Uusitupa, Matti (2017)
    Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.