Biomarkers in blood

Recently developed techniques and acquired knowledge on the regulation of blood parameters known to be involved in signaling satiety and satiation - such as cholecystokinin, glucose, insulin, leptin, GLP-1 and others - enable the measurement of physiological correlates of satiation and satiety. In addition to these 'classic' parameters, new techniques can be used to find biomarkers of satiety. Nuclear magnetic resonance (NMR) spectroscopy combined with pattern recognition is a promising technique to identify potential biomarkers in blood and urine. With NMR techniques, a broad range of compounds with different physico-chemical properties can be detected simultaneously. Sophisticated statistical software is needed to explore patterns in NMR data. From these patterns it is possible to nominate potential biomarkers. Fractionation of the samples and subsequent NMR liquid chromatographic and mass-spectrometric analysis on the fractions will elucidate the structure of the biomarkers. In addition, proteomics, metabolomics and transcriptomics are promising techniques that can be used for identifying biomarkers of satiety (Werf et al., 2001). Transcriptomics and proteomics can be employed to determine changes in gene expression and proteome relevant to the state of hunger or satiety. One such example has recently been published: consuming a breakfast relatively high in protein resulted in higher concentrations of ghrelin, glucagon, gastric inhibitory peptide (GIP), CCK and GLP-1 compared with consuming a breakfast relatively high in carbohydrates (Blom et al., 2005). These conditions also differentially affected lymphocyte gene expression. Consumption of the high-carbohydrate breakfast resulted in expression of glycogen metabolism genes, whereas consumption of the high-protein breakfast resulted in expression of genes involved in protein biosynthesis (Van Erk et al., 2006).

Hunger and satiety: relation to body weight control 37 2.5.2 Central biomarkers

There is limited knowledge of how the brain contributes to the regulation of food intake in humans. After eating, the human brain senses a biochemical change and then signals satiation, but precisely when this occurs is unknown. With respect to central nervous system biomarkers of satiety and satiation, there have been a number of recent studies in the literature using imaging techniques. The two most important techniques used to study appetite are positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) (Berns, 1999). These studies have identified various regions in the brain that can distinguish between fasted state and that after food ingestion (for example, Liu et al., 2000; Smeets et al., 2005a, 2005b). Some studies suggest that the responses of the brain to a meal differ between obese and lean individuals (Matsuda et al., 1999; Gautier et al., 2000). The rapid development of brain imaging techniques during the past decade, however, provides non-invasive methods enabling the investigation of brain function in response to various stimuli. The applicability of these techniques is limited, because specific and expensive technology is required and only specific brain areas may be investigated.

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