Specific adaptation of gastric emptying to diets with differing protein content in the rat: is endogenous cholecystokinin implicated?

BACKGROUND: Recent studies indicate that gastric emptying may be influenced by patterns of previous nutrient intake. Endogenous cholecystokinin (CCK), whose synthesis and release can be affected by dietary intake, has a major role in the regulation of gastric emptying. AIMS: To evaluate the influence of diets with differing protein content on gastric emptying of differing liquid test meals and plasma CCK levels in the rat and to check whether the inhibitory effect of exogenous CCK on gastric emptying is modified after long term intake of diets with differing protein content. METHODS: Rats were fed for three weeks with high protein, medium protein (regular), or low protein diet. On day 22 gastric emptying of a peptone meal was studied. In addition, basal and postprandial CCK levels after the different dietary regimens were measured by bioassay. The time course of dietary adaptation was studied and its specificity assessed through the use of different (peptone, glucose, and methylcellulose) test meals. The effect of exogenous CCK-8 on gastric emptying was studied at the end of the adaptation period (three weeks). RESULTS: Feeding the animals with a high protein diet for three weeks resulted in a significant (p < 0.05) acceleration (by 21.2 (8.2)%) of gastric emptying while feeding with a low protein diet was followed by a significant (p < 0.05) delay (by 24.0 (6.2)%) in the emptying rate. When the time course of the effect of dietary adaptation on gastric emptying was studied, it appeared that at least two weeks are required for dietary protein to be effective. The regulatory effect of dietary protein on gastric emptying proved to be dependent on meal composition. Only the emptying rate of a protein containing meal (40% peptone) was significantly modified by previous dietary intake. No significant (p > 0.05) changes were observed with glucose and methylcellulose meals whose emptying rates were similar in rats receiving a high protein or low protein diet. A peptone meal strongly and significantly (p < 0.05) increased plasma CCK levels in rats fed a medium protein (regular) diet. Results were similar in rats receiving a low protein diet (p < 0.05) but not in rats on a high protein diet (p > 0.05). As a consequence, postprandial plasma levels of CCK in rats fed with a medium or low protein diet were significantly (p < 0.05) higher than those in rats receiving a high protein diet. In rats on high and low protein diets, dose response curves to CCK-8 were virtually identical, suggesting that dietary protein intake has no influence on the effect of exogenous CCK. CONCLUSIONS: These results clearly show that gastric emptying of a protein containing meal can be modified by previous dietary protein intake. This effect, which is time dependent and meal specific, may be related to changes in endogenous CCK release which will affect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, these results emphasise the importance of dietary history in the evaluation and interpretation of gastric emptying data.

Butyrate enhances major histocompatibility complex class I, HLA-DR and ICAM-1 antigen expression on differentiated human intestinal epithelial cells.

Besides its metabolic role, butyrate, a by-product of colonic fermentation, can modulate colonocyte proliferation and the expression of various molecules. In inflammatory bowel diseases, epithelial cells express HLA class II molecules and may behave as antigen-presenting cells. This study was performed to characterize the effect of butyrate on major histocompatibility complex expression by human colonocytes in comparison with interferon-gamma. Five cell lines displaying different differentiation features were analysed for antigen expression by flow cytofluorimetry. All lines expressed class I antigens, whereas only SW 1116 cells express HLA-DR. On these cells, butyrate and interferon-gamma strongly enhanced HLA-DR and ICAM-1 expression, whereas a mild increase in class I antigens was noted. Moreover, an increase in class I antigens was observed on two other differentiated cell lines, and it was synergistic with interferon-gamma. Butyrate, by its modulation of HLA-DR, ICAM-1 and HLA class I expression, may act on antigen presentation and, thus, influence some inflammatory processes.

Leukemia inhibitory factor (LIF) and oncastsin M (OSM) high affinity binding require additional receptor subunits besides GP130 and GP190.

The structure of Leukaemia Inhibitory Factor (LIF) and Oncostatin M (OSM) receptors is not completely resolved. Heterodimerization of gp190 and gp130 has been proposed to form a high affinity receptor (type I) shared by LIF and OSM, while heterodimerization of gp130 with an as yet unidentified subunit is proposed to form a high affinity OSM receptor (type II) not shared by LIF. We have analysed the binding stoichiometries, cross-competition properties and cross-linking patterns of LIF and OSM to the choriocarcinoma JAR cell line. The data obtained are not fully accounted for by the model proposed above. They indicate rather that third chains of 140-150 kDa molecular mass, in addition to the gp130 and gp190 subunits, enter in the structure of LIF and OSM high affinity receptors. These results were strongly supported by transfection experiments in CHO cells. CHO cells co-transfected with the human gp190 and gp130 cDNAs expressed high affinity LIF receptors but no high-affinity OSM receptors, indicating that an additional component is required for high affinity OSM binding. High-affinity LIF cross-linking on these cells also showed the association of LIF with a 150 kDa component in addition to the gp130 and gp190 subunits.

[Expression of the gene of cholecystokinin. Demonstration from duodenal biopsies in man]. / Expression du gène de la cholécystokinine. Mise en évidence à partir de biopsies duodénales chez l'homme.

Cholecystokinin (CCK) is a peptide released after feeding. Until now, CCK gene expression has been studied only on sacrified animals on mucosa scrapped off the duodenum. OBJECTIVE--The aim of this study was to assess CCK-mRNA detection on duodenal biopsy specimens in subjects undergoing gastrointestinal endoscopy. METHODS--Six biopsy specimens were taken from 6 healthy subjects, a) after a 12-h overnight fast and b) 6 or 12 h after a fat meal, and inducing a CCK release. CCK-mRNA was analyzed by Northern blot. RESULTS--Plasma CCK levels increased from basal levels of 0.5 +/- 0.1 pmole/L to 8.2 +/- 1.5 pmole/L 10 min after the meal. The fasting CCK-mRNA levels were 44.0 +/- 0.6% and the post-prandial levels increased to 74.0 +/- 6.0% at 6 h and decreased to 47.5 +/- 0.5% at 12 h. CONCLUSIONS--Detection of CCK gene expression in human duodenal biopsy specimens is feasible. Stimulation of CCK release after a meal is followed by an increase in CCK-mRNA in the duodenal mucosa.

The effects of cyclosporine on HILDA/LIF gene expression in human T cells.

We examined the effect of cyclosporine on HILDA/LIF gene expression in alloreactive human T lymphocyte clones (ATLCs) 2B11 and 2F7 obtained from cells infiltrating a rejected human kidney graft. Both ATLCs were stimulated either by the specific antigen or by PMA + calcium ionophore in the presence of various concentrations of CsA (10-500 ng/ml). Inhibition of HILDA/LIF gene expression was analyzed at the protein level using a proliferative assay on the HILDA/LIF-dependent Da-1a cell line and by RNA blotting using a specific probe. Without CsA, the kinetics of mRNA accumulation for both ATLCs peaked at 5 and 10 hr, respectively, after mitogenic and antigenic stimulations. HILDA/LIF activity peaked at 24 and 72 hr, respectively, after mitogenic and antigenic stimulation in supernatants from both ATLCs and decreased thereafter. Subsequent experiments with CsA were thus performed at these time points. Our results show that HILDA/LIF mRNA accumulation and protein secretion in 2B11 and 2F7 clones were strongly inhibited in a dose-dependent manner by CsA, in both stimulation conditions. Maximal inhibition of HILDA/LIF transcripts and protein secretion (60-90%) was observed within the range of 75-500 ng/ml CsA.