Gastrointestinal targets of appetite regulation in humans.

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.

Impact of some isoenergetic snacks on satiety and next meal intake in healthy adults.

BACKGROUND: Choosing small portions especially of low energy foods is a standard recommendation for weight management. However, this can result in rapid return of hunger or an increase in the next meal size. Enhancing the satiating capacities of low energy foods may help to overcome these effects. The present study compared the satiating properties of small servings of four low energy foods [465 kJ (111 kcal)] including a drinking yogurt enhanced for satiety. METHODS: Thirty volunteers attended the laboratory to consume isoenergetic preloads of: a fibre-enriched drinking yogurt, a regular drinking yogurt, plain crackers, fresh banana; or an isovolumetric serving of water. Satiety was analysed using visual analogue scales, before and every 15 min after consumption for 60 min, when ad libitum food intake was measured. RESULTS: The yogurts and the banana were more satiating than water and crackers (P < 0.001 for yogurts and banana versus crackers and water). Only the fibre-enriched yogurt produced higher satiety scores than crackers at 60 min (P < 0.05). Mean + or - SD consumption at next meal was: fibre-enriched yogurt 2050 + or - 787 kJ (490 + or - 188 kcal); regular yogurt 2071 + or - 575 kJ (495 + or - 137 kcal); bananas 2178 + or - 603 kJ (520 + or - 144 kcal); crackers 2232 + or - 590 kJ (533 + or - 141 kcal); water 2519 + or - 741 kJ (602 + or - 177 kcal); (yogurts versus water: P = 0.001; bananas versus water: P = 0.013; crackers versus water: P = 0.064), demonstrating accurate energy compensation for the yogurts only. CONCLUSIONS: Although there were no significant differences between the different foods' satiating capacity, a trend for the following ranking was found: fibre-enriched yogurt > regular yogurt > banana > crackers > water. Overall, the fibre-enriched drinking yogurt tended to be more satiating than the other foods.

The role of Teashirt in proximal leg development in Drosophila: ectopic Teashirt expression reveals different cell behaviours in ventral and dorsal domains.

Localised transcription factors specify the identity of developmental domains. Here we analyse the function of the Teashirt zinc finger protein, which is expressed in the proximal domain of the Drosophila leg. By ectopic expression of a teashirt transgene we show that Teashirt contributes to the differences in cell-cell adhesion between proximal and distal leg cells. Whereas clones of cells expressing the teashirt transgene survive in the endogenous Teashirt domain, most cells expressing Teashirt in an ectopic distal position are lost from the epithelium. In clones which were recovered in the distal domain, different effects were seen dependent on position with respect to the dorsal-ventral axis. In the ventral region, where Wingless is signalling, surviving clones express Teashirt and cause abnormalities in the adult leg. Contrarily, lateral and dorsal clones generally do not accumulate Teashirt and have no effect on patterning. One exception to the differential dorsal-ventral effects occurs at the boundary between Teashirt-expressing and -nonexpressing cells. Both ectopic and hypomorphic loss of teashirt affects patterning at all positions at the boundary, suggesting that Teashirt plays a crucial role in boundary formation. The results are discussed with respect to the roles of transcriptional and posttranscriptional mechanisms in proximal-distal axis patterning of the Drosophila legs.

The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila.

Wnt signalling is a key pathway for tissue patterning during animal development. In Drosophila, the Wnt protein Wingless acts to stabilize Armadillo inside cells where it binds to at least two DNA-binding factors which regulate specific target genes. One Armadillo-binding protein in Drosophila is the zinc finger protein Teashirt. Here we show that Wingless signalling promotes the phosphorylation and the nuclear accumulation of Teashirt. This process requires the binding of Teashirt to the C-terminal end of Armadillo. Finally, we present evidence that the serine/threonine kinase Shaggy is associated with Teashirt in a complex. We discuss these results with respect to current models of Armadillo/beta-catenin action for the transmission of the Wingless/Wnt pathway.

Trunk-specific modulation of wingless signalling in Drosophila by teashirt binding to armadillo.

BACKGROUND: One function of the Wingless signal cascade is to determine the 'naked' cuticle cell-fate choice instead of the denticled one in Drosophila larvae. Wingless stabilises cytoplasmic Armadillo, which may act in a transcriptional activator complex with the DNA-binding protein T-cell factor (also known as Pangolin). As these components are critical for all Wingless-dependent patterning events, the problem arises as to how specific outputs are achieved. RESULTS: The Teashirt zinc finger protein was found to be necessary for a subset of late Wingless-dependent functions in the embryonic trunk segments where the teashirt gene is expressed. Teashirt was found to be required for the maintenance of the late Wingless signalling target gene wingless but not for an earlier one, engrailed. Armadillo and Teashirt proteins showed similar Wingless-dependent modulation patterns in homologous parts of each trunk segment in embryos, with high levels of nuclear Teashirt and intracellular Armadillo within cells destined to form naked cuticle. We found that Teashirt associates with, and requires, Armadillo in a complex for its function. CONCLUSIONS: Teashirt binds to, and requires, Armadillo for the naked cell-fate choice in the larval trunk. Teashirt is required for trunk segment identity, suggesting that Teashirt provides a region-specific output to Armadillo activity. Further modulation of Wingless is achieved in homologous parts of each trunk segment where Wingless and Teashirt are especially active. Our results provide a novel, cell-intrinsic mechanism to explain the modulation of the activity of the Wingless signalling pathway.