Use of Metabolomics to Discover Metabolic Patterns Associated with Human Diseases

Now that complete genome sequences are available for a variety of organisms, the elucidation of gene functions involved in metabolism necessarily includes a better understanding of cellular responses upon mutations on all levels of gene products, mRNA, proteins, and metabolites. Such progress is essential since the observable properties of organisms – the phenotypes – are produced by the genotype in juxtaposition with the environment. Whereas much has been done to make mRNA and protein profiling possible, considerably less effort has been put into profiling the end products of gene expression, metabolites. To date, analytical approaches have been aimed primarily at the accurate quantification of a number of pre-defined target metabolites, or at producing fingerprints of metabolic changes without individually determining metabolite identities. Neither of these approaches allows the formation of an in-depth understanding of the biochemical behaviour within metabolic networks. Yet, by carefully choosing protocols for sample preparation and analytical techniques, a number of chemically different classes of compounds can be quantified simultaneously to enable such understanding. In this review, the terms describing various metabolite-oriented approaches are given, and the differences among these approaches are outlined. Metabolite target analysis, metabolite profiling, metabolomics, and metabolic fingerprinting are considered. For each approach, a number of examples are given, and potential applications are discussed.

Although diet and nutrition are widely believed to play an important part in the development of Type II (non-insulin-dependent) diabetes mellitus, specific dietary factors have not been clearly defined. Much controversy exists about the relations between the amount and types of dietary fat and carbohydrate and the risk of diabetes. In this article, we review in detail the current evidence regarding the associations between different types of fats and carbohydrates and insulin resistance and Type II diabetes. Our findings indicate that a higher intake of polyunsaturated fat and possibly long-chain n-3 fatty acids could be beneficial, whereas a higher intake of saturated fat and trans-fat could adversely affect glucose metabolism and insulin resistance. In dietary practice, exchanging nonhydrogenated polyunsaturated fat for saturated and trans-fatty acids could appreciably reduce risk of Type II diabetes. In addition, a low-glycaemic index diet with a higher amount of fiber and minimally processed whole grain products reduces glycaemic and insulinaemic responses and lowers the risk of Type II diabetes. Dietary recommendations to prevent Type II diabetes should focus more on the quality of fat and carbohydrate in the diet than quantity alone, in addition to balancing total energy intake with expenditure to avoid overweight and obesity.

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown. Here we show that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding.