Abstract

Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.

Highlights

  • Obesity is characterized by excess body fat, which is predominantly stored in adipose tissue

  • Insulin resistance, diabetes, dyslipidaemia and fatty liver tend to co-occur in the same individual, it has been useful to refer to this cluster of manifestations as ‘metabolic syndrome’

  • It is clear that there is a high prevalence of metabolic disturbances in individuals with schizophrenia and other psychotic disorders (Saarni et al, 2009; Suvisaari et al, 2007)

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Summary

Introduction

Obesity is characterized by excess body fat, which is predominantly stored in adipose tissue. Insulin resistance, diabetes, dyslipidaemia and fatty liver tend to co-occur in the same individual, it has been useful to refer to this cluster of manifestations as ‘metabolic syndrome’ The clustering of these pathologies is not considered a random event: rather, they probably have common pathogenic mechanisms. According to a systems biology view, most of the genetic component of complex disease susceptibility is not individual genes, but in their interactions with other genes and with the environment (Tang et al, 2009) In this context, the measurement of traits that are modulated but not encoded by the DNA sequence – commonly referred to as intermediate phenotypes (Meyer-Lindenberg and Weinberger, 2006) – is of particular interest. The metabolome is sensitive to both genetic and environmental factors, which makes metabolomics a powerful phenotyping tool for personalized medicine

Assessing individuals versus populations
The lipidome in health and disease
Detecting early markers of metabolic disorders
Increased vulnerability to inflammation
Conclusions
Findings
Forthcoming DMM articles
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