The role of cholecystokinin in the expression of seasonal variation in the feed intake and eating pattern of red deer (Cervus elaphus).

The role of cholecystokinin (CCK) in the expression of seasonal variation in feed intake and feeding activity in ruminants was investigated by active immunisation of castrated male red deer (Cervus elaphus). In April, animals of two groups (five animals per group) were immunised against either CCK or vehicle solution only and booster injections were administered at 2-month intervals for the following year. Measurements were conducted for a period of more than a year from July. There were no significant effects of immunisation on mean daily food intake. However, there was a significant interaction (P<.01) between immunisation and month (season), with respect to rate of feed ingestion during meals, with animals immunised against CCK exhibiting higher mean rates of ingestion during October to May but lower mean rates during June to September. It is concluded that systemic CCK has a role in the expression of seasonal variation in the rate of feed ingestion during meals in ruminants and that this, in turn, may affect the pattern of seasonal change in daily feed intake. Since there was no evidence of differences with treatment in profiles of insulin, growth hormone (GH), thyroxine (T(4)), triiodothyronine (T(3)), insulin-like growth factor-1 (IGF-1) or prolactin, it is unlikely that this effect is expressed through changes in the profiles of these hormones.

Impact of feeding regimen on behavioral and physiological indicators for feeding motivation and satiety, immune function, and performance of gestating sows.

The effect of daily or interval (every 3 d) feeding on body weight change, blood glucose and cholecystokinin (CCK) concentrations, immune function, and behavioral activity were determined during the gestation period of sows. Sows were fed a corn-soybean meal diet either 2 kg daily or 6 kg once every 3rd d (interval). Body weight changes for the 42-d trial period were not different (P > .05) between regimens. Blood glucose concentrations were similar before feeding (P > .05). Two hours after feeding, glucose concentrations increased in interval-fed sows but not in daily-fed sows (P < .05). Premeal plasma CCK concentrations were greater for daily-fed sows than for interval-fed sows (P < .05). The CCK concentrations in sows of both regimens increased after feeding above premeal levels (P < .05), and interval-fed sows exhibited higher concentrations than daily-fed sows (P < .05). Immune function as evaluated through mitogen-induced proliferation of T cells was greater in daily-fed sows than in interval-fed sows (P < .05). Daily-fed sows were more active overall and on any given day than interval-fed sows (P < .05) and thus seemed to expend more energy. Further, daily-fed sows exhibited higher levels of mouth-based activities (i.e., sham chewing, licking, appetitive and consummatory feeding behavior, and excess drinking) than sows restricted to consumption of one large meal every 3rd d. These indicators suggest that feeding motivation significantly affected overall performance of sows. This study emphasizes the need for evaluating the impact of feeding regimens and meal size on feeding motivation and, ultimately, on the well-being of the gestating sows.

Immunogenicity of cholecystokinin octapeptide-conjugated antigens in pigs.

An improved antigen is required to raise antiserum titers against cholecystokinin higher than those observed in previous studies to demonstrate the effect of immunoneutralization of cholecystokinin on feed intake in swine. Four immunogenic carrier proteins were compared. Unsulfated cholecystokinin octapeptide (CCK8ns) was conjugated to each of human serum globulin (HSG), BSA, Keyhole limpet hemocyanin (KLH), and Tuberculin purified protein derivative (PPD). Forty crossbred swine (four from each of 10 litters, 78 d of age, 22 kg BW) were randomly assigned to the four conjugated antigens by litter. The primary and three booster doses of antigen were injected at 14-d intervals. A blood sample was drawn before the primary dose on d 1 to assess basal nonspecific binding of antigen. Additional blood samples were drawn on d 22, 29, 36, 43, 50, 57, 71, and 92 to follow the time course of antiserum titer expression (d 1 = day of primary dose). Titer is the serum dilution that binds 50% of 1 fmol of radiolabeled antigen. Titers, compared by ANOVA of log titer values, were different between antigens (P < .01) and between litters (P < .01). Mean titer (n = 40; 10 pigs, four samples/pig) during the period after the immune response (d 50, 57, 71, and 92) was 55, 115, 176, and 535 for BSA, HSG, KLH, and PPD, respectively. It is concluded that the carrier protein component has an important effect on immunogenicity of conjugated CCK antigens in pigs; BSA was inferior and KLH and PPD were superior to HSG.

Cholecystokinin octapeptide immunization: effect on growth of barrows and gilts.

A study was conducted to validate the previously reported growth response to cholecystokinin octapeptide (CCK-8) immunization in barrows and was extended to include gilts. Group-penned barrows and gilts were used to represent conditions in the swine industry. Thirty-two animals, 19 barrows and 13 gilts, were randomly assigned by sex to four pens and two treatments. The control groups were immunized with human serum globulin (hSG). The treated groups (CCK) were immunized with the C-terminal octapeptide of cholecystokinin conjugated to human serum globulin. Specific binding of CCK-8 was confirmed at 29 d after the primary inoculation. Antisera titers were highly variable throughout. The mean titer reached a peak on d 57 and then declined. Body weight gains during the last 49 d, the period during which titers were expressed, were compared by ANOVA. The treatment effect on gain was significant (P = .018); the sex effect approached significance (P = .071); the treatment x sex interaction effect was not significant (P = .82). Least squares mean gain of the CCK group was 8.4% greater than of the hSG group, 41.4 vs 38.2 kg, respectively. A significant linear regression coefficient for gain vs antisera titer was obtained for barrows (P = .03; r2 = .44) but not for gilts. Several carcass variables showed trends similar to that of BW gain, but the treatment effects were less robust (P < .05 to .10). These results generally confirm the findings of the previous study; CCK-8 immunization stimulated growth of barrows by 7.5% in the present and by 10.8% in the previous study.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cholecystokinin immunization, enhanced food intake and growth of swine on lean yield and carcass composition.

It was previously reported that cholecystokinin (CCK) immunization of swine increased food intake 8.2% and rate of growth 10.6%. This report compares carcass yields of lean, fat and bone tissues of CCK-immunized vs. human serum globulin (hSG) control animals. The experiment involved 24 castrated pigs, age 75 d, weight 25.6 kg, randomly assigned to the CCK-immunized or hSG control groups (2 pigs/pen, 6 pens/group). Food was offered for ad libitum access. Carcasses of CCK-immunized animals (vs. hSG controls) were 8.7% heavier (P less than 0.01) and 2.4% longer (P less than 0.01). Carcass yield and composition were analyzed by dissection to lean, fat and bone fractions and by proximate analysis of the resultant lean fraction. Carcasses from the CCK-immunized animals had 2.7 kg more lean (P = 0.09) and 1.8 kg more fat (P = 0.04). Proximate analysis indicated there were no significant differences in composition of the lean fraction. The 7.2% heavier lean fractions of the CCK-immunized animals contained 9.2% more protein (P = 0.09) and 5.1% more fat (P = 0.05). Lean:fat and protein:fat ratios were not significantly altered.

Principal gastrointestinal variables associated with metabolic heat production in pigs: statistical cluster analyses.

The purpose of this study was to classify organs/tissues into clusters according to their association with fasting heat production (FHP) by multivariate cluster analysis and to identify primary tissues. A data set consisting of 47 variables and 2256 data points was collected from 48 growing male pigs. Variance was perturbed by varying the daily feed allowance. Cluster analysis was conducted at each of six levels of body dissections, and a final analysis was conducted with all 47 variables. Small intestine, pancreas, liver, and kidneys were consistently assigned to the FHP-cluster; stomach, cecum, and colon to clusters correlated, r greater than 0.5, to the FHP-cluster; carcass, thoracic and offal variables to unrelated clusters. In the final analysis with all 47 variables represented, only variables from the small intestine and jejunum were assigned to the FHP-cluster. It is concluded that the small intestine, which accounts for only 2% of the body weight, is a primal organ system in swine and that pancreas, liver, and kidneys are of similar importance.

Specific heat output (SHO) of visceral organs/tissues: the hypothesis and first estimations.

It was hypothesized that each organ/tissue has a characteristic specific heat output (SHO; kcal/d.g). Heat output (HO; kcal/d) is defined as the product of the SHO and the weight, g, of the organ/tissue. FHP (fasting heat production) is defined as the sum of HO values of all tissues of fasted animals. FHP and organ weight were perturbed by variations of food intake of 48 young swine before FHP and weights of 36 organ/tissue variables were measured. Cluster analysis was used to group the variables and simplify the analyses and indicated that small intestine, kidneys, liver and pancreas were principal sources of FHP. Regression estimates indicated that the SHO of pancreas and kidneys was high (1.1 to 1.9), that of small intestine, liver and colon was intermediate (.21 to .26), and that of stomach and lungs was low (.11 to .14). All other viscera tissues were assumed to have SHO near that for nonviscera, estimated at .0165 kcal/d.g. Mean values of FHP and empty body weight were 1856 kcal/d and 46,651 g respectively; thus the mean SHO value of all tissues was about .04 kcal/d.g. The SHO values of stomach, intestine, colon, pancreas, kidneys, liver and lungs were in the range 3- to 50-fold greater than SHO of the whole body and in the range 7- to 120-fold greater than the estimated SHO of the nonviscera. These findings indicate that the small intestine, liver and kidneys account for about 60% of HO from viscera or about 30% of total FHP.

Stimulation of food intake and growth of swine by cholecystokinin immunization.

Experimental superalimentation at 30% above ad libitum intake increased growth 40% and confirmed that voluntary food intake is a growth-limiting factor in swine. A sequence of contingent hypotheses was proposed for swine: cholecystokinin (CCK) is a regulator of food intake; food intake is enhanced by reduction of serum CCK; serum CCK is reduced by anti-CCK antibodies: anti-CCK antibodies are raised by active immunization. The objectives of this study were to determine if antibodies were raised in immunized swine and if the anti-CCK titers were sufficient to increase food intake and growth. Twelve young growing swine were immunized against cholecystokinin (CCK-8) to test the hypothesis that anticholecystokinin antibodies in serum would suppress cholecystokinin inhibition of appetite (food intake). An equal number of control animals (hSG) were immunized against the antigenic carrier protein by the same protocol. Specific binding of [125I]CCK-8, the C-terminal octapeptide, by sera diluted 1:181 increased to a peak value on day 43. Food intake and body weight gain were similar for the two groups during the first phase of the study. However, food intake was 8.2% greater and body weight gain was 10.6% greater for the CCK-8 than for the hSG group during the second phase (d 43 to d 77). Total food intake over the 77-day study was 5.4% greater for the CCK-8 group (P = .08): body weight gain was 8.3% greater (P = .006). Regression analyses confirmed that gain over the 34-day second phase increased .076 kg (P = .045; R2 = 0.34) for each percentage unit increase of serum binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune, growth and carcass responses of ram lambs to active immunization against desulfated cholecystokinin (CCK-8).

This study explored feed intake and carcass responses to active immunization against desulfated cholecystokinin-octapeptide (CCK-8) in ram lambs. Antibody titers 8 wk following primary immunization and booster immunizations given at 4 and 6 wk averaged greater than 1:1,000. Titers increased to greater than 1:10,000 by 16 wk following a final booster immunization at 11 wk. The antibodies developed against desulfated CCK-8 exhibited 29% and 13% cross-reactivities for sulfated CCK-8 and gastrin-17, respectively. Immunization against desulfated CCK-8 had no effect on feed intake, ADG, carcass weight or carcass quality grade. Backfat thickness and carcass yield grade were reduced (P less than .05) by immunization. Organ weights at slaughter, including those of the pancreas and small intestines, were not affected by CCK-8 immunization, with the exception of the lungs, which were 16% lighter (P less than .01) in immunized lambs. In conclusion, active immunization against desulfated CCK-8 resulted in development of high antibody titers against desulfated and sulfated CCK-8. Immunization against CCK-8 decreased fat content of the carcass but failed to affect feed intake, carcass weight or ADG.

Morphometry of the intestine of the pig. I. A method for complete circumsection analysis.

A method and scheme are described to improve precision for quantitation of functional aspects of the intestine by morphometric evaluation of a representative sample hereafter called a circumsection. A circumsection is defined as: all tissue lying within the total circumference of a slice of the intestinal wall transected at a righ angle to the long axis of the intestine tube. The quantitative values obtained from these substantial specimens therefore provide a basis for reliable estimations of the organ content of specified cellular masses or of functional surfaces, ie, villi volume, epithelial surface, crypt mass, muscle mass, etc. The volume, mass, or area of specialized cells can be compared with physiological functions and capacities. These comparisons and relationships are important to investigate the causes and effects of digestion-absorption parameters on performance output of healthy animals--growth, development, reproduction, lactation, work output, etc. The data can also describe responses of the digestive organs (tissues) to various inputs--dietary, environmental, chemical, and physical. The method involves analysis of a montage of photomicrographs of the circumsection. The method was successful; the data collected demonstrated that the small intestine of the pig has lateral symmetry (left vs right) but is asymmetrical in the opposite plane (mesenteric vs antimesenteric). The asymmetry is especially clear in the ileum and jejunum where significant differences between opposite halves ranged from 7% to 90% of the mean value.

Morphometry of the intestine of the pig. II. Circumsection response to feeding schedules.

Weight measurement of the gastrointestinal organs (GIT) and morphometric measurements of circumsections of the small intestine (SI) have demonstrated profound responses to the level of dietary intake. The average response of pigs (all the same live body weight) gaining weight at a moderate rate (treatment LH) relative to pigs losing weight (HL) were as follows (+ denotes increase): GIT weight, +71.5%; SI weight, +84.8%; tissue fraction of SI mucosa, +16.0%; index of quantity of mucosa per SI circumsection, +64.7%; estimate of the mass of mucosa in the whole SI organ, +108%. Although the composition of circumsections from duodenum, jejunum, and ileum differed substantially and significantly, the effects of treatments were similar at each site. Of the 542-g response (LH vs HL) of the small intestine, estimates calculated from circumsection morphometry data indicate that 55 g, 11 g, and 476 g were from muscle, matrix, and mucosa, respectively. Changes in the size of the circumsection were much greater than changes in composition. The shift in the quantity of mucosa in the circumsection was about fourfold greater than would have been predicted from the tissue fraction of mucosa. The relationship between the morphometric responses and biochemical functions of the mucosa are important to understand digestive-absorptive capacities and nutrient requirements during and immediately after a major shift in food intake.

Animal growth during liberation from appetite suppression.

Superalimentation (SA) of swine at 120% (ad libitum = 100%) for 23 days elicited a 40% greater gain of body mass (P less than .005) than littermate control (C) pigs. The accretion of lean and fat tissues during this excess and rapid growth were about the same as if the animal were allowed to attain the same weight over a longer period by conventional feeding practices. Superalimentation is defined as feed intake distinctly in excess of normal voluntary intake on a grams-dry-matter-per-kilogram-body-weight basis. The substantial body mass response shows that growth is limited by a lack of nutrient intake (appetite) during normal ad libitum feeding. Either digestion-absorption processes are not saturated during normal feed intake or digestion and absorption capacities are enhanced during excess food intake; furthermore, either cellular hyperplasia or hypertrophy are not regulated by inherited neuroendocrine factors or cellular growth is somehow released from neuroendocrine regulation during periods of excess circulating nutrients. The overall gain efficiency (kg total gain per kg total alimentation dry matter) during superalimentation was slightly improved (7.3%) but was not significant. Efficiency of the differential gain (delta gain/delta dry matter intake; delta = SA-C) was 25% higher than the overall gain efficiency of the C pigs (0.374 vs 0.300 kg/kg) and suggests that the additional nutrients may have been utilized for growth with greater efficiency than nutrient consumed ad libitum.

A method for direct gastric feeding and the effect on voluntary ingestion in young swine.

The purpose of the study was to determine the effect of direct administration of diet into the stomach on total alimentation (quantity consumed voluntarily plus the quantity administered by young pigs. Ten cross-bred pigs, 82 days of age, were assigned to five treatments (two replicates of five pigs) consisting of a control (C) and four gastric fistulated (GF) pigs. The GF pigs were fed daily via the fistula 0, 20, 40 and 60% of the dry matter consumed voluntarily by the control pigs (17h per day). Relative to the control pigs, the GF-0, GF-20, GF-40 and GF-60 pigs, respectively, ate 102.4, 99.9, 91.7 and 97.3% the quantity of diet and gained 116.7, 111.1, 113.0 and 114.8% body weight; thus, the surgery, device and procedures were not detrimental. Voluntary consumption was physiologically regulated rapidly with good precision to adjust for the gastric fistula administered diet. Correlation and regression analysis of daily voluntary ingestion (y) versus gastric administration (x) of the six GF-20, -40 and -60 pigs gave a correlation coefficient, r = -0.926 (P less than 0.01), and regression coefficient, b= -1.089 (0.10 greater than P greater than 0.05). The statistical coefficients indicate that voluntary ingestion was suppressed somewhat more than the quantity administered into the stomach.

Effects of plane of nutrition on organ size and fasting heat production in pigs.

Twenty-seven 12-week-old barrows with average initial weight of 27 kg were randomly assigned to three treatments. The first group (HL) was fed to gain 19 kg body weight during the first 35 days (period 1) and to lose 5 kg during the second 35 days (period 2). The second group (MM) was fed to gain 7 kg during both periods 1 and 2. The third group (LH) was fed to lose 5 kg during period 1 and to gain 19 kg during period 2. At the end of the 70-day period, 7 pigs from each treatment were fasted for 30 hours and fasting heat production (FHP) was measured by indirect calorimetry. The animals were slaughtered and weights of stomach, small and large intestine, liver, pancreas, spleen, kidneys and heart were measured. Although all animals had the same final body weight, animals on the higher plane of nutrition during period 2 had significantly higher FHP and higher weights for stomach, small and large intestine, pancreas, liver and kidneys. FHP and the weights of small intestine, pancreas and liver from animals receiving the higher plane of nutrition during period 2 (LH) were 50% heavier than that from animals on low plane (HL). Positive correlations exist between FHP and weights of stomach, small intestine, large intestine, pancreas, liver and kidneys. These results indicate that prior nutritional history significantly influences FHP, which is highly correlated to weights of metabolically active organs.

Influence of high-fiber diet on bacterial populations in gastrointestinal tracts of obese- and lean-genotype pigs.

Bacterial populations from gastrointestinal tracts of genetically lean and obese pigs fed a low- or high-fiber diet (0 or 50% alfalfa meal, respectively) were enumerated with rumen fluid media and specific energy sources. Total culture counts in rectal samples declined 56 (P greater than 0.05) and 63% (P less than 0.05) in lean and obese animals, respectively, 3 weeks after feeding the high-fiber diet. After 8 weeks, culture counts had risen and were similar to those obtained before alfalfa was fed (0 week). At slaughter, 12 to 17 weeks after feeding the high-fiber diet, total counts from rectal samples of lean pigs continued to rise and were 13% greater than the 0-week counts, whereas counts from obese animals declined 37% (P greater than 0.05). The number of cellulolytic bacteria in rectal samples of lean-genotype pigs fed the high-fiber diet increased 80 and 71% from 0 to 3 weeks and 3 to 8 weeks, respectively. This overall increases from 0 to 8 weeks in lean pigs was significant (P less than 0.05); however, these increases were not seen in obese pigs. These data suggest that the microflora is initially suppressed when exposed to a high-fiber diet and that later some adaptation takes place, apparently more so in lean than in obese pigs. When specific energy sources were used to delineate the distribution of different bacterial populations in the cecum, colon, and rectum, trends could be detected between high- and low-fiber diets. These data also support the concept that bacteria populations from different sites in the large bowel differ.

Gastrointestinal metabolism and transport of pesticidal carbamates.

Published evidence pertaining to gastrointestinal absorption and metabolism of pesticidal carbamates will be reviewed. The major body of evidence will come form investigations conducted by the author on N-methylcarbamate pesticides with rats; few investigations directly involving the gastrointestinal system have been reported by other research groups. Results derived from in vitro and isolated in vivo preparations show that pesticidal carbamates are absorbed and metabolized by gastrointestinal tissues. Numerous gastrointestinal metabolites have been separated; some have been identified and their behavior in the gut characterized; these data will be included in the review to the extent they have been published. The absorptive and metabolic capacities of the gastrointestinal system vary from one region to another. The author draws from evidence obtained from in vitro and in vivo studies and proposes the events that occur between carbamate ingestion and the appearance of the compound and/or its metabolites in the portal blood or mesenteric lymph. In this endeavor, the author acknowledges that superimposition of the metabolic precursory substrate-product sequence on the sequential physiologic steps from ingestion to defecation produces a complex situation which is difficult if not impossible to study meaningfully by investigation of one tissue component at a time (i.e., epithelial uptake, epithelial metabolism, mucosal to serosal transport, etc.).

Propachlor detoxication in the small intestine: cysteine conjugation.

14C-labeled 2-(S-cysteinyl)-N-isopropylacetanilide was recovered from the media of everted sacs of rat small intestine incubated in media that contained [14C] propachlor (2-chloro-N-isopropyl-[1(-14) C]acetanilide). The metabolite was identified on the basis of chromatographic characteristics and mass spectra of the butyl ester-trifluoro-acetamide derivative. This evidence shows that the cysteinyl conjugate was formed during incubations of the small intestine. Although the glutathione conjugate has not been isolated from the intestine, it is a likely precursor of the cysteinyl metabolite. Data from experiments conducted with 10(-5) and 10(-4) M propachlor in the media showed that the capacity to metabolize propachlor to polar metabolites was approximately the same throughout the length of the small intestine.

Rat intestinal metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate).

Everted sacs of rat small intestine metabolized crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) under in vitro conditions to form six 14C-labeled metabolites in quantities sufficient for isolation and identification. These metabolites were 4-tert-butyl-2-chlorophenyl methyl phosphoramidate (25%), 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenyl methyl methylphosphoramidate (19%), 2-[3-chloro-4-[[(methoxy) (methyl-amino)phosphoinyl]oxy]phenyl]-2-methylpropionic acid (2%), 4-tert-butyl-2-chlorophenol (0.8%) and its glucuronide (6%), and the aromatic glucuronide of 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenol (1%). These intestinal metabolites may represent precursory stages in the overall metabolism of crufomate.