Raw soya-bean flour increases cholecystokinin release in man

1. The aim of the present study was to determine whether oral ingestion of raw soya-bean flour, which contains trypsin inhibitors, alters the release of cholecystokinin (CCK) in man. 2. Eleven healthy volunteers ate two mixed meals: one with raw soya-bean flour and the other with soya-bean flour that had been heat-treated. The two flours inhibited 34 and 3 mg trypsin/g flour respectively. 3. CCK was measured in plasma using a bioassay based on the release of amylase (EC 3.2.1.1) from dispersed rat pancreatic acini. 4. The peak CCK response was 16.8 (SE 8.1) pmol/l with raw soya-bean flour but 4.9 (SE 2.8) pmol/l with heat-treated flour (P less than 0.05). 5. We conclude that ingestion of raw soya-bean flour increases CCK release in man and that heat treatment which reduces the trypsin inhibitor content of the flour also diminishes its CCK-releasing effect.     

Coffee stimulation of cholecystokinin release and gallbladder contraction in humans

We studied the effect of the ingestion of 400 mL regular coffee on plasma cholecystokinin (CCK) concentrations and of 165 mL regular and decaffeinated coffee on plasma CCK and gallbladder contraction in six healthy regular coffee drinkers. Plasma CCK concentrations rose 3.3 +/- 0.4 pmol/L after 400 mL and 2.8 +/- 0.9 pmol/L after 165 mL regular coffee compared with 1.8 +/- 0.6 pmol/L after 165 mL decaffeinated coffee. These plasma CCK increments were greater than those after 400 and 165 mL of an isosmotic and isothermic sodium chloride solution (0.6 +/- 0.2 and 0.4 +/- 0.1 pmol/L, respectively). An average gallbladder contraction of 33 +/- 7% was observed after 165 mL regular coffee and 29 +/- 10% after 165 mL decaffeinated coffee, whereas after 165 mL sodium chloride the contraction was only 10 +/- 12%. We conclude that both regular coffee and decaffeinated coffee give rise to increments in plasma CCK and contractions of the gallbladder.     

Differences in cholecystokinin release and gallbladder contraction between emulsified and nonemulsified long-chain triglycerides.

BACKGROUND: Fat is a potent stimulus of cholecystokinin (CCK) release. Apart from lipolysis, fatty acid chain length, and saturation, emulsification may also determine the magnitude of CCK release. METHODS: We have studied the effect of emulsification of soybean oil on CCK and pancreatic polypeptide (PP) release (radioimmunoassay [RIA]) and gallbladder motility (ultrasonography). Six healthy subjects were studied on three separate occasions in random order during (1) intraduodenal administration of emulsified long-chain triglycerides (LCT) (6 mmol/h for 120 minutes); (2) equimolar amounts of nonemulsified LCT with addition of emulsifier; and (3) saline with emulsifier (control). RESULTS: Intraduodenal administration of both nonemulsified LCT and emulsified LCT induced significant (p < .05) increases in plasma CCK and PP levels and reductions in gallbladder volume. However, compared with nonemulsified LCT, emulsified LCT resulted in a readier and significantly stronger CCK release (212+/-62 pmol/L per 120 minutes vs 36+/-7 pmol/L per 120 minutes; p < .05); PP release (2034+/-461 pmol/L per 120 minutes vs 671+/-106 pmol/L per 120 minutes; p < .05); and gallbladder contraction (77%+/-2% vs 41%+/-7%; p < .05). No significant alterations were observed in plasma CCK or PP levels and gallbladder volume during administration of saline with emulsifier. CONCLUSIONS: Intraduodenal administration of a low-dose emulsified LCT more potently stimulates CCK and PP release and gallbladder contraction in comparison to equimolar amounts of nonemulsified LCT. These findings point to an important role for solubilization of LCT in determining the magnitude of CCK release from the intestine.     

Medium-chain triglycerides and long-term parenteral nutrition in children.

There are no data concerning long-term utilization of medium-chain triglycerides (MCTs) in parenteral nutrition (PN) in children. Our study included 12 children, aged 1.5-17 yr, on total PN at home, supplying a daily intake of 214 +/- 92 mg/kg nitrogen and 47 +/- 17 kcal/kg nonprotein energy (NPE). NPE included 10-32% long-chain triglycerides (LCTs) (Intralipid 20%). After switching to emulsion containing 50% MCT and 50% LCT (Medialipide) at the same dosage regimen and infusion rate as before, the subjects were monitored at 1, 3, and 6 mo. No signs of clinical intolerance were observed. Among the laboratory parameters evaluated, the only significant (p < 0.05) changes were 1) an increase in apolipoproteins A-I and A-II at 1, 3, and 6 mo and 2) a decrease in gamma-glutamyltransferase (gamma-GT) at 6 mo. There were no changes in the status of essential fatty acids in plasma or in phospholipids (in erythrocyte membranes). Moderate urinary excretion of dicarboxylic acids (adipic, suberic, and sebacic) was evidence of peroxysomal omega-oxidation. The results support the proposal for use of MCT-rich emulsion in long-term PN, given its metabolic advantages relative to LCT.     

Physical state of meal affects gastric emptying, cholecystokinin release and satiety

To verify the influence of food consistency on satiety mechanisms we evaluated the effects of the same meal in solid-liquid (SM) and homogenized (HM) form on satiety sensation, gastric emptying rate and plasma cholecystokinin (CCK) concentration. Eight healthy men, aged 21-28 (mean 24.5) years were given two meals (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, total energy 2573 kJ, with water 300 ml) differing only in physical state: SM and HM. The subjects consumed the meals in randomized order on non-consecutive days. The sensations of fullness, satiety and desire to eat were evaluated by means of a questionnaire, gastric emptying was assessed by ultrasonographic measurement of antral area, and plasma CCK concentration was measured by radioimmunoassay. The vegetable-rich meal was significantly more satiating (P < 0.05) when in the HM form than when eaten in a SM state. Furthermore, the overall gastric emptying time was significantly slowed (255 (SEM 11) min after HM v. 214 (SEM 12) min after SM; P < 0.05) and CCK peak occurred later (94 (SEM 12) min after HM v. 62 (SEM 11) min after SM; NS) when the food was consumed in the HM form. Independently of the type of meal, antral area was significantly related to fullness sensations (r2 0.46, P = 0.004). These results demonstrate that meal consistency is an important physical food characteristic which influences both gastric emptying rate and satiety sensation. Moreover, the relationship observed between antral area and fullness sensation confirms that antral distension plays a part in the regulation of eating behaviour.     

Incorporation of dietary triacylglycerols from olive oil and high-oleic sunflower oil into VLDL triacylglycerols of hypertensive patients.

OBJECTIVES: To establish whether the ingestion of diets enriched with olive oil or high-oleic sunflower oil may produce changes in the composition of VLDL triacylglycerols from hypertensive patients. It could be relevant for the uptake and metabolism of triacylglycerol-derived metabolites by extrahepatic tissues. DESIGN: Patients were assigned to the diets in a random-order sequence. SUBJECTS: The participants were 24 hypertensive patients recruited from a religious community. INTERVENTIONS: The study was conducted over two four week periods with a four week washout period between both MUFA diets. RESULTS: Dietary olive oil kept in balance the content of saturated fatty acids and decreased the content of arachidonic acid in VLDL triacylglycerols. HOSO diet reduced the content of palmitic acid and increased the content of linoleic acid. There was also a decrease in trioleate-glycerol and an increase in tripalmitate-glycerol of VLDL after the MUFA diets, but these effects were more pronounced in the HOSO group. Intake of olive oil decreased the content of disaturated triacylglycerols and increased the content of dioleate-containing triacylglycerols. A decrease in palmitate-dioleate-glycerol after dietary HOSO was observed. Olive oil (but not HOSO) promoted the presence of long-chain PUFA of n-3 family at the sn-2 position of VLDL triacylglycerols. CONCLUSIONS: Our data indicate that olive oil and HOSO, providing a similar concentration of MUFA (oleic acid), differ in the formation of VLDL triacylglycerols in hypertensive patients.     

The soybean beta-conglycinin beta 51-63 fragment suppresses appetite by stimulating cholecystokinin release in rats

We previously demonstrated that soybean beta-conglycinin peptone suppresses food intake and gastric emptying by direct action on rat small intestinal mucosal cells to stimulate cholecystokinin (CCK) release. The aim of the present study was to define the active fragment in beta-conglycinin by using synthetic peptides chosen from the sequence of three beta-conglycinin subunits. We selected the fragments that had multiple nonadjacent arginine residues, and investigated their ability to bind to components of the rat intestinal brush border membrane as well as to stimulate CCK release and appetite suppression. The fragment from 51 to 63 of the beta subunit (beta 51-63) had the strongest binding activity. Intraduodenal infusion of beta 51-63 inhibited food intake and markedly increased portal CCK concentration. The threshold concentration of beta 51-63 to affect food intake was 3 micro mol/L. The CCK-A receptor antagonist abolished the beta 51-63-induced suppression of food intake. Three types of smaller fragments of beta 51-63 (beta 51-59, beta 53-63 and beta 53-59) and two types of fragments similar to beta 51-63 in the beta-conglycinin alpha and alpha' subunits (alpha 212-224 and alpha' 230-240) had less binding ability than did beta 51-63. Model peptides constructed with arginine (R) and glycine (G), such as GRGRGRG, had strong binding affinity, but peptides containing a single R or RR did not. These results indicate that the beta-conglycinin beta 51-63 fragment is the bioactive appetite suppressant in beta-conglycinin, and multiple arginine residues in the fragment may be involved in this effect.     

Effect of different long-chain fatty acids on cholecystokinin release in vitro and energy intake in free-living healthy males

Long-chain fatty acids have been shown to suppress appetite and reduce energy intake (EI) by stimulating the release of gastrointestinal hormones such as cholecystokinin (CCK). The effect of NEFA acyl chain length on these parameters is not comprehensively understood. An in vitro screen tested the capacity of individual NEFA (C12 to C22) to trigger CCK release. There was a gradient in CCK release with increasing chain length. DHA (C22) stimulated significantly (P < 0.01) more CCK release than all other NEFA tested. Subsequently, we conducted a randomised, controlled, crossover intervention study using healthy males (n 18). The effects of no treatment (NT) and oral doses of emulsified DHA-rich (DHA) and oleic acid (OA)-rich oils were compared using 24 h EI as the primary endpoint. Participants reported significantly (P = 0.039) lower total daily EI (29 % reduction) with DHA compared to NT. There were no differences between DHA compared to OA and OA compared to NT. There was no between-treatment difference in the time to, or EI of, the first post-intervention eating occasion. It is concluded that NEFA stimulate CCK release in a chain length-dependent manner up to C22. These effects may be extended to the in vivo setting, as a DHA-based emulsion significantly reduced short-term EI.     

Nickel deficiency and nickel-rhodium interaction in chicks.

Nickel deficiency was produced in chicks under near optimal growth conditions. This judgment is based on the finding that chicks fed the experimental diet supplemented with nickel had a very satisfactory growth rate, over 600 g in 4 weeks. To induce nickel deficiency, chicks were raised in plastic cages located inside plastic isolators and were fed diets (containing 2-15 ng of nickel/g) based on dried skim milk, acid-washed ground corn, EDTA-extracted soy protein, and corn oil. In 2 experiments, controls were fed 3 mug of nickel/g as NiCl2-6H2O. In experiment 3, instead of 1 control group 25, 50, 250, and 2,500 ng/g of supplemental dietary nickel as NiCl2-6H2O were each given to separate groups of chicks. Nickel deprivation resulted in: ultrastructural changes in the liver with the most obvious abnormality in the organization of the rough endoplasmic reticulum; altered gross appearance, reduced oxidative ability, and decreased lipid phosphorus in the liver; altered shank skin pigmentation that was associated with a decrease in yellow lipochrome pigments; and lower hematocrits. Deficiency also tended to increase the thickness of the legs and size of the hock; decrease the length:width ratios of the tibias and femurs; and decrease the plasma cholesterol. None of the signs of deficiency were seen in chicks fed diets containing at least 52 ng of nickel/g. In one experiment, a group of birds was fed 50 mug of rhodium/g of diet as (ClRh(NH3)5)SO4 to ascertain whether rhodium is a metabolic antagonist of nickel. Supplemental rhodium increased the hematocrits and liver oxidative ability of both nickel-deficient and -supplemented chicks, and increased total liver lipids, liver lipid phosphorus, and liver cholesterol in the nickel-deficient chicks alone. Rhodium did not increase the signs of nickel deficiency.     

Studies on the plasma cholesterol and triacylglycerols in chronic methemoglobinemia in rats.

Plasma cholesterol and triacylglycerols were measured in rats with modelled chronic two-stage (mild and moderate) intermittent nitrite methemoglobinemia for 15 and 30 days. It was found that at the moment of methemoglobinemic peak (60 +/- 10 min) the experimental animals had mixed (hemtoxic, anemic and hypoxic) hypoxemia. The every day "pulse" decrease of the total oxygen concentration during the 30-day methemoglobinemia was accompanied with a significant rise (p < 0.05) of cholesterol concentrations in the high-density lipoproteins and the total cholesterol, as well as a decrease in the amount of triacylglycerols. These changes are considered to represent the side effects of adaptation for whose elucidation further research is needed.     

Medium-chain fatty acid nanoliposomes suppress body fat accumulation in mice

Medium-chain fatty acids (MCFA) are widely used in diets for patients with obesity. To develop a delivery system for suppressing dietary fat accumulation into adipose tissue, MCFA were encapsulated in nanoliposomes (NL), which can overcome the drawbacks of MCFA and keep their properties unchanged. In the present study, crude liposomes were first produced by the thin-layer dispersion method, and then dynamic high-pressure microfluidisation (DHPM) and DHPM combined with freeze-thawing methods were used to prepare MCFA NL (NL-1 and NL-2, respectively). NL-1 exhibited smaller average size (77.6 (SD 4.3) nm), higher zeta potential (- 40.8 (SD 1.7) mV) and entrapment efficiency (73.3 (SD 16.1) %) and better stability, while NL-2 showed narrower distribution (polydispersion index 0.193 (SD 0.016)). The body fat reduction property of NL-1 and NL-2 were evaluated by short-term (2 weeks) and long-term (6 weeks) experiments of mice. In contrast to the MCFA group, the NL groups had overcome the poor palatability of MCFA because the normal diet of mice was maintained. The body fat and total cholesterol (TCH) of NL-1 (1.54 (SD 0.30) g, P = 0.039 and 2.33 (SD 0.44) mmol/l, P = 0.021, respectively) and NL-2 (1.58 (SD 0.69) g, P = 0.041 and 2.29 (SD 0.38) mmol/l, P = 0.015, respectively) significantly decreased when compared with the control group (2.11 (SD 0.82) g and 2.99 (SD 0.48) mmol/l, respectively). The TAG concentration of the NL-1 group (0.55 (SD 0.14) mmol/l) was remarkably lower (P = 0.045) than the control group (0.94 (SD 0.37) mmol/l). No significant difference in weight and fat gain, TCH and TAG was detected between the MCFA NL and MCFA groups. Therefore, MCFA NL could be potential nutritional candidates for obesity to suppress body fat accumulation.     

Biological activity of 24,25-dihydroxycholecalciferol in chicks and rats.

The ability of 24R, 25- and 24S, 25-dihydroxycholecalciferol to stimulate intestinal calcium transport and bone calcium mobilization in chicks was measured. Enhancement of intestinal calcium transport by 325 or 130 nmoles of either compound was maximal by 24 hours. The effects of these compounds on bone calcium mobilization were also maximal by 24 to 36 hours. When lower doses were tested, 2 nmoles of the 24R, 25-dihydroxycholecalciferol significantly stimulated intestinal calcium transport, whereas 130 nmoles of the S isomer were required for a significant response. Neither steroid had a significant effect on bone calcium mobilization when doses of less than 130 nmoles were given. When chicks received orally 32.5, 325 or 1,625 pmoles of 24R, 25-dihydroxycholecalciferol daily from hatching for 4 weeks, several parameters showed a dose-related response. These included growth, serum calcium, bone ash, renal 25-hydroxycholecalciferol-1-hydroxylase and intestinal vitamin D-dependent calcium binding protein. Rats given 32.5 to 1,625 pmoles of 24R, 25-dihydroxycholecalciferol for 3 or 6 weeks were equivalent to vitamin D-treated controls in terms of growth and serum calcium levels. It is concluded that within the lower dose ranges (2 to 30 pmoles) the R isomer of 24,25-dihydroxycholecalciferol is more active in stimulating intestinal calcium transport than the S isomer but that neither compound increases bone calcium mobilization at these dose levels. Also, the rat is more responsive in terms of growth and serum calcium, to small dialy doses of 24R, 25-dihydroxycholecalciferol than is the chick.     

Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators

BACKGROUND: Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the food chain; they also have long biological half-lives. OBJECTIVES: Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. METHODS: We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor alpha (ER-alpha)-deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of beta-hexosaminidase. RESULTS: All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha. CONCLUSIONS: Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens.     

Lipotoxic effects of triacylglycerols in J774.2 macrophages

OBJECTIVE: Triacylglycerols (TGs) are being considered as an independent risk factor in atherosclerosis and metabolic syndrome, acting by dysregulation of the TG/high-density lipoprotein axis. Accumulation of lipids in subendothelial space attracts macrophages, leading to atherosclerotic plaque formation and increased plaque instability due to formation of foam cells and macrophage death. The aim of this study was to evaluate lipotoxic effects in macrophages caused by TG uptake. METHODS: J774.2 macrophages were exposed to soybean or olive oil-based lipid emulsions as a source of TGs (1 mg/mL) in a presence or absence of lipase inhibitor paraoxon (20 microM) or to bovine serum albumin-complexed palmitic (150 microM), linoleic (600 microM), and oleic (600 microM) fatty acids. RESULTS: The results demonstrated accumulation of TGs, G1/S arrest, and cell death with necrotic morphologic features after exposure to TG emulsions. These effects were prevented by treatment with an antioxidant N-acetyl-cysteine (0.5 mM). Paraoxon inhibited intracellular TG degradation but did not prevent lipotoxicity and cell death. Olive oil TG triggered macrophage death in a manner similar to soybean oil. Treatment of the macrophages with free fatty acid, mainly with palmitic acid, showed a reactive oxygen species-independent cell death pathway, which was different from that of TG and was not prevented by N-acetyl-cysteine. CONCLUSION: This study shows a direct lipotoxic pathway for TG molecules in macrophages, which is not associated with degradation of TG molecule to free fatty acids. This study for the first time can explain at a cellular level how TGs as an independent risk factor aggravate atherosclerotic outcomes.     

Involvement of food intake in the lysine-arginine antagonism in chicks.

Studies were conducted to evaluate the involvement of food intake in the lysine-arginine antagonism. Diets were formulated to compensate for the metabolic consequences of excess dietary lysine; induction of renal arginase activity, depression of heptic glycine transamidinase, and urinary losses of arginine. This was accomplished by inclusion of creatine in the basal diet, use of a moderate excess of lysine that did not increase urinary arginine excretion, and addition of the arginase depressors, alpha-aminoisobutyric acid (AIB) and L-threonine, to diets containing excess lysine. When chicks were fed diets containing excess lysine ad libitum, growth and efficiency of arginine retention were reduced. Supplementation of the diets with AIB and threonine markedly reduced the growth depression and restored efficiency of arginine utilization. When chicks were force-fed the diet containing excess lysine, growth was depressed, and body composition was altered. Inclusion of AIB and threonine in the diet containing excess lysine resulted in growth and body composition equivalent to levels of force-fed controls. In a second experiment the basal diet and basal supplemented with AIB and threonine were pair-fed to lysine-supplemented diets containing AIB and threonine. Body weight gains and body composition of all groups were similar. In other experiments, food intake increased within 24 hours (P less than 0.05) and probably within 12 hours (P less than 0.10) after removal of excess lysine from the diet. It is concluded that a portion of the lysine-arginine antagonism is due to a primary effect of lysine on regulation of food intake.