Fasting and refeeding cause rapid changes in intestinal tissue mass and digestive enzyme capacities of Atlantic salmon (Salmo salar L.)

Fasting and refeeding effects on gastrointestinal morphology and digestive enzyme activities of Atlantic salmon, held in tanks of seawater at 9 degrees C and 31 per thousand salinity, were addressed in two trials. Trial 1: Fish (mean body mass 1190 g) were fasted for 40 days and intestines sampled at day 0, 2, 4, 11, 19 and 40. Trial 2: Fish (1334 g), fasted for 50 days, were refed and sampled at day 0, 3 and 7. Mass, length, protein, and maltase, lactase, and leucine aminopeptidase (LAP) activities were analyzed for stomach (ST), pyloric caeca (PC), proximal (PI), mid (MI), and distal intestine (DI). PC contributed 50% of gastrointestinal mass and 75% of enzyme capacity. Fasting decreased mass and enzyme capacities by 20-50% within two days, and 40-75% after 40 days. In PC, specific brush border membrane (BBM) maltase activity decreased whereas BBM LAP increased during fasting. Upon refeeding, enzyme capacities were mostly regenerated after one week. The results suggest that refeeding should start slowly with about 25% of estimated feed requirement during the first 3 days, but may then be stepped up rapidly. Investigations of digestive processes of fed fish should only be performed when intestines are feed-filled to avoid bias due to effects of fasting.     

Short-term fasting induces intra-hepatic lipid accumulation and decreases intestinal mass without reduced brush-border enzyme activity in mink (<Emphasis Type="Italic">Mustela vison</Emphasis>) small intestine

For many mammalian species short-term fasting is associated with intestinal atrophy and decreased digestive capacity. Under natural conditions, strictly carnivorous animals often experience prey scarcity during winter, and they may therefore be particularly well adapted to short-term food deprivation. To examine how the carnivorous gastrointestinal tract is affected by fasting, small-intestinal structure, brush-border enzyme activities and hepatic structure and function were examined in fed mink (controls) and mink that had been fasted for 1–10 days. During the first 1–2 days of fasting, intestinal mass decreased more rapidly than total body mass and villus heights were reduced 25–40%. In contrast, tissue-specific activity of the brush-border enzymes sucrase, maltase, lactase, aminopeptidase A and dipeptidylpeptidase IV increased 0.5- to1.5-fold at this time, but returned to prefasting levels after 6 days of fasting. After 6–10 days of fasting there was a marked increase in the activity of hepatic enzymes and accumulation of intra-hepatic lipid vacuoles. Thus, mink may be a useful model for studying fasting-induced intestinal atrophy and adaptation as well as mechanisms involved in accumulation of intra-hepatic lipids following food deprivation in strictly carnivorous domestic mammals, such as cats and ferrets.Communicated by I.D. Hume     

Effect of starvation and refeeding on digestive enzyme activities in juvenile roach, Rutilus rutilus caspicus

We evaluated the effects of starvation and refeeding on digestive enzyme activities in juvenile roach, Rutilus rutilus caspicus. Fish were divided into four feeding groups (mean mass 1.68 ± 0.12 g). The control group was fed to satiation twice a day throughout the experiment with formulated diet (SFK). The other three groups were deprived of feed for 1(S1), 2(S2), and 3(S3) weeks, respectively, and then fed to satiation during the refeeding period. The results showed that trypsin specific activity was not affected significantly either by starvation or refeeding, in all experimental groups. Chymotrypsin specific activity did not change significantly in S1 fish during the experimental period. In S2 and S3 fish no significant changes were observed during the starvation period. Upon refeeding, the activity increased in S2 fish, while it decreased in S3 fish. Amylase specific activity decreased significantly during the starvation period in all experimental groups. Upon refeeding, the activity increased. Alkaline phosphatase specific activity did not change significantly during the experiment period in S3 fish, while it showed significant changes during the starvation and refeeding period in the S1 and S2 fish. Starvation also had a significant effect on the structure of the intestine.     

Brown fat activity in fasted and refed rats

Four days of fasting in the rat reduced brown-adipose-tissue (BAT) mass, mitochondrial protein, and tissue protein content. Specific binding of guanosine diposphate (GDP) to BAT mitochondria was depressed by 55% in 4d-fasted rats. Rats fasted for 3 d, and then refed a single carbohydrate meal (40 kJ), showed a significant increase in specific GDP-binding (27% above fasted) 24 h later, and a large increase in total binding. Specific activities of cytochrome oxidase and -glycerophosphate dehydrogenase in BAT mitochondria were not significantly affected by fasting or refeeding. These results suggest that BAT may be partly responsible for the fall in metabolic rate associated with fasting and the delayed increase after carbo-hydrate refeeding. These effects may be due to changes in the mitochondrial proton-conductance pathway in brown fat.     

Effect of starvation and refeeding on digestive enzyme activities in sturgeon (Acipenser naccarii) and trout (Oncorhynchus mykiss)

The digestive enzyme activities were determined in Adriatic sturgeon and rainbow trout during starvation and refeeding period. Overall, the digestive enzyme activities are affected in the same sense in both species. The protease and lipase activities were decreased later than amylase activity. Even after 1 month of starvation, both species would be prepared to digest protein and lipids in an effective way. After 72 days of starvation, the digestive machinery of the sturgeon and of the trout shows an altered capacity to digest macronutrients. The capacity to digest proteins and lipids, after 60 days of refeeding, begins to become re-established in sturgeon and trout. In contrast, in this period, the capacity to digest carbohydrates remains depressed in both species.     

Physiological and morphological responses to the first bout of refeeding in southern catfish (Silurus meridionalis)

Many animals experience fasting because of the high temporal and spatial sporadicity of food availability. Once food is available, animals use external energy to restore their depressed functional performance. In the present study, the physiological and morphological responses to the first bout of refeeding in juvenile southern catfish (Silurus meridionalis) were characterized. Fish that had undergone long-term fasting (fasted for 32 days, the S32 group) exhibited a lower resting metabolic rate ( $ {\dot{\text{M}}} $ O_2rest decreased by 49 %), lower peak metabolic rate ( $ {\dot{\text{M}}} $ O_2peak decreased by 24 %), greater energy expenditure (increased by 15 %) during specific dynamic action (SDA) and longer duration SDA response (increased by 41 %) than those of a control group (S0 group, fasted for 0 days). The S32 group showed a significantly reduced peak gastric evacuation rate (0.131 g meal h^?1) compared with the S0 group (0.315 g meal h^?1). The S0 group also had a shorter gastric evacuation time (36 h) than either of the two fasting groups (both 64 h). The S32 group displayed a higher minimum gastric pH (3.1) than the S0 and S16 groups (2.6). Refeeding did not trigger an increase in the wet mass of the gastrointestinal tract, whereas the liver wet mass of the S0 and the two fasting groups increased significantly with refeeding. The trypsin and lipase of the S0 group showed higher mass-specific activities and organ capacities than either of the two fasting groups at certain specific time points. A similar result was found for aminopeptidase activity. Multiple loach meals equaling 6 % of the body weight of the fed fish completely restored the liver morphology within the S16 but not the S32 group. Our results suggest that the regulation of the digestive performance of the gastrointestinal tract in S. meridionalis that are finishing their first small meal after fasting is delayed compared with that of nonfasting fish and that it is similar to the characteristics (lower $ {\dot{\text{M}}} $ O_2peak, greater SDA and a longer duration of the SDA response) of the refeeding SDA.     

Physiological responses to short-term fasting among herbivorous,omnivorous, and carnivorous fishes

We explored the integrated role of dietary specialization and feeding periodicity on the response of the gastrointestinal tract of teleosts fishes to short-term (7–10 days) fasting and refeeding. Fasted and fed herbivorous grass carp (Ctenopharyngodon idella), omnivorous channel catfish (Ictalurus punctatus), and carnivorous largemouth bass (Micropterus salmoides) were compared for digestive organ masses, intestinal morphology, gastrointestinal pH, and the specific activities and total intestinal capacities of the intestinal hydrolases aminopeptidase (APN) and maltase and intestinal nutrient transporters. All three species experience intestinal hypertrophy with feeding as noted by significant increases in enterocyte dimensions. Of the three, only I. punctatus experienced a postprandial increase in intestinal length, and only C. idella experienced significant modulation of intestinal microvillus length. Feeding resulted in acidification of the stomachs of I. punctatus and M. salmoides. Predicted to exhibit a relatively modest set of postprandial responses because of their more frequent feeding habits, C. idella only experienced increases in APN and maltase activity with feeding and no significant regulation of nutrient uptake. Significant regulation of hydrolase activities and nutrient uptake were exhibited by I. punctatus and M. salmoides, with I. punctatus experiencing the most comprehensive set of responses. As predicted by food habits, there was an interspecific gradient in intestinal length and glucose uptake extending from longer intestines and greater glucose uptake for the herbivorous C. idella, intermediate lengths and glucose uptake for the omnivorous I. punctatus, and shorter intestines and reduced glucose uptake for the carnivorous M. salmoides. Among teleosts fishes, short episodes of fasting lead to significant alterations in intestinal form and function that are rapidly restored with feeding.     

Maturation of the intestinal digestion and of microbial activity in the young rabbit: impact of the dietary fibre:starch ratio

The developmental changes of intestinal digestive potential and caecal microbial activity were described in suckling and weaned rabbits according to two feeding programmes. Two groups of thirteen litters were fed from 18 to 42 days old a “High” or a “Medium” NDF:starch ratio diet (resp. 2.7 vs 2.0, groups HL and ML) with similar protein and lipid levels, and from 42 to 70 days old the two groups were fed a “Low” NDF:starch ratio diet (1.7). From 25 to 32 days (weaning), the milk and solid feed intake were 22% and 41% higher in ML group (P < 0.05), and the mortality by diarrhoea was 4 units lower (P < 0.01). The whole tract digestive efficiency increased by 10% before weaning, and remained steady (organic matter) or decreased (lipids, protein) after weaning. Energy digestibility was 0.623 and 0.686 for High and Medium diets respectively. From 25 to 42 days, total enzymatic activity in intestinal content increased for chymotrypsin (5-fold, P < 0.001), lipase (10-fold, P < 0.001), amylase (17-fold, P < 0.01) and maltase (11-fold, P < 0.001), while trypsin doubled after weaning. The feeding programme only affected the amylase and maltase activities, that were higher in HL group (P < 0.05). The volatile fatty acids concentration in the caecum was not significantly different among the groups, but it increased by 44% 10 days after weaning. The bacterial fibrolytic enzymes, increased by 30% after weaning and were similar among the two groups. The study revealed that the intestinal digestive maturation and the caecal microbial activity of the rabbit evolved markedly between 3 and 5 weeks of age, and was weakly affected when the NDF:starch ratio decreased from 2.7 to 2.0.     

Cortisol increases the activities of intestinal apical membrane hydrolases and nutrient transporters before weaning in mink (Mustela vison)

Glucocorticoids from endogenous and exogenous sources accelerate maturation of brush-border membrane (BBM) hydrolases in omnivorous laboratory rodents and pigs. Less is known for carnivores, and whether the route of administration (oral or systemic) has an influence. The present study examined the influence of administering cortisol (hydrocortisone succinate, 5 mg/kg-day) to mink during postnatal week 4, just prior to weaning, on small intestine glucose and amino acid (aspartate, leucine, lysine, methionine, proline) absorption and on the activities of BBM disaccharidases and peptidases. Kits treated with cortisol were smaller (P<0.05), but had small intestines that were proportionally larger (P<0.05 for length and mass per kg body weight, but not for mucosal mass) than control kits with higher rates of absorption for most nutrients, except leucine, and increased activities of most BBM hydrolases, except lactase. As a consequence, cortisol increased hydrolytic and absorptive capacities of the entire small intestine, with the responses more pronounced when the cortisol was given orally. These findings indicate administration of cortisol stimulates growth of the developing mink small intestine, but does not accelerate the postnatal declines in nutrient transport, and may be a dam-to-kit signal that prepares suckling mink to digest and absorb the adult diet.     

Quantitation by immunoblotting of the in vivo induction and subcellular distribution of hepatic acetyl-CoA carboxylase

The in vivo induction of rat liver acetyl-CoA carboxylase (ACC) the rate-limiting enzyme of fatty acid biosynthesis, has been examined by immunoblotting, avidin blotting, and enzyme isolation. Three high-molecular-weight immunoreactive bands (Mr 220,000-260,000) were recognized in liver extracts by an anti-carboxylase polyclonal antiserum. Two bands, A and B, comigrated on sodium dodecyl sulfate polyacrylamide gels with purified acetyl-CoA carboxylase, were avidin binding, and were dramatically induced following high carbohydrate refeeding. Only band A was recognized on immunoblots using a monoclonal antibody directed against acetyl-CoA carboxylase, suggesting that band B is a proteolytic fragment in which the epitope recognized by the monoclonal antibody is absent. Following refeeding, approximately 57% of acetyl-CoA carboxylase mass (band A + band B) was present in the high-speed supernatant fraction, while 34 and 9% were in the high-speed (microsomal) and low-speed pellet fractions, respectively. Refeeding caused a large increase in total acetyl-CoA carboxylase mass, the magnitude of which differed in the various fractions. In the low-speed supernatant, a 20-fold increase in ACC mass was observed, while a 12-fold increase was seen in the high-speed supernatant. The fold increase in the high-speed pellet was even greater (greater than 27-fold). Acetyl-CoA carboxylase purified by avidin-Sepharose chromatography from fasted/refed rats had an approximate 4-fold higher Vmax and a significantly lower Ka for citrate than enzyme purified from fasted animals. The results of this study indicate that the induction of hepatic ACC that occurs during high carbohydrate refeeding of the fasted rat predominantly involves increases in enzyme content in both cytosol and microsomes, but is also accompanied by an increase in enzyme specific activity.     

Expression of hepatic calcium-binding protein regucalcin mRNA is elevated by refeeding of fasted rats: Involvement of glucose,insulin and calcium as stimulating factors

The effect of refeeding on the expression of Ca²⁺-binding protein regucalcin mRNA in the liver of fasted rats was investigated. When rats were fasted overnight, the hepatic regucalcin mRNA level was reduced about 70% of that in feeding rats. Refeeding produced a remarkable elevation of hepatic regucalcin mRNA level (about 150–170% of fasted rats). Liver regucalcin concentration was appreciably increased by refeeding, although it was not altered by fasting. The oral administration of glucose (2 g/kg body weight) to fasted rats caused a significant increase in hepatic regucalcin mRNA level. Moreover, hepatic regucalcin mRNA level was clearly elevated by a single subcutaneous administration of insulin (10 and 100 U/kg) to fasted rats. The hormonal effect was not further enhanced by the simultaneous administration of calcium chloride (250 mg Ca/kg) to fasted rats, although calcium administration stimulated regucalcin mRNA expression in the liver. The present study suggests that the expression of hepatic regucalcin mRNA stimulated by refeeding is significantly involved in the action of insulin and/or calcium as stimulating factors.     

Phenotypic flexibility of digestive system in Atlantic cod (Gadus morhua)

This study examined the restoration of the digestive capacity of Atlantic cod (Gadus morhua Linnaeus) following a long period of food deprivation. Fifty cod (48 cm, 1 kg) were food-deprived for 68 days and then fed in excess with capelin (Mallotus villosus Müller) on alternate days. Ten fish were sampled after 0, 2, 6, 14 and 28 days and the mass of the pyloric caeca, intestine and carcass determined. Two metabolic enzymes (cytochrome c oxidase and citrate synthase) were assayed in white muscle, pyloric caeca and intestine, and trypsin activity was measured in the pyloric caeca. A delay of 14 days was required before body mass started to increase markedly, whereas most of the increase in mass of both the pyloric caeca and intestine relative to fish length occurred earlier in the experiment. By day 14, the activities of trypsin and citrate synthase in the pyloric caeca as well as citrate synthase in the intestine had reached maxima. The growth of the digestive tissues and restoration of their metabolic capacities thus occur early upon refeeding and are likely required for recovery growth to take place. The phenotypic flexibility of the cod digestive system is therefore remarkable: increases in trypsin activity and size of pyloric caeca resulted in a combined 29-fold increase in digestive capacity of the fish during the refeeding period. Our study suggests that Atlantic cod are able to cope with marked fluctuations in food availability in their environment by making a rapid adjustment of their digestive capacity as soon as food availability increases.     

Kidney-specific enzyme expression by human kidney cell lines generated through oncogene transfection.

The human kidney cell line 293 was generated by transfection of adenovirus DNA into normal human embryonic kidney (HEK) cells (Graham et al., 1977), whereas the human kidney cell lines ST-1i and STt-4i were generated by transfection of HEK cells with plasmids encoding SV40 viral oncogenes (Abcouwer et al., 1989). In this study, we examined kidney-specific enzyme activity levels in 293, ST-1i, and STt-4i cells to determine their ability to exhibit kidney-specific gene expression. Enzymes examined were leucine aminopeptidase (LAP), gamma-glutamyl transpeptidase (gamma-GTP), and the disaccharidases trehalase and maltase. Enzymatic activity levels were compared to three other kidney cell lines (MDCK, OK, and LLC-PK1) as well as to normal human embryonic kidney (HEK) cells and the human hepatoma cell line, Hep G2. Modulation of kidney-specific enzyme activities was assessed in response to several differentiation-inducing agents (adenosine, n-butyric acid, hexamethylene bisacetamide (HMBA), dimethyl sulfoxide (DMSO), N,N'-dimethylformamide (DMF), isobutyl methyl xanthine (IBMX), di butyryl cAMP, and retinoic acid). ST-1i and STt-4i exhibit elevated levels of LAP, gamma-GTP, trehalase, and maltase, consistent with their kidney cell origin, whereas 293 cells exhibit elevated levels of just gamma-GTP and maltase. Maltase and gamma-GTP enzyme activities in ST-1i and STt-4i cells were very responsive to the various inducing agents; 293 cells were less responsive at the inducer concentrations examined. None of the three human cell lines formed domes under any of the experimental conditions. In summary, ST-1i and STt-4i are comparable to normal HEK cells in expression of kidney-specific enzymes and in responsiveness to differentiation-inducing agents, in spite of continued expression of SV40 oncogenes.     

Effect of fasting on body composition and responses to stress in sunshine bass

The integrated responses of the hormonal regulation of growth and stress in sunshine bass (Morone chrysops X Morone saxatilis) as regulated by feed deprivation were investigated. Groups of fish were fed 1.5% of the body weight per day or offered no feed for 4 weeks. Another group of fish was not fed for 3 weeks and feed was offered during the fourth week. Fish in each group were sampled immediately before or after a 15-min low water confinement stressor after each week of the experiment. Liver mass and liver glycogen content were decreased after one week of fasting and remained low until the end of the study. However, both recovered after a week of refeeding. Intraperitoneal fat was significantly lower after two weeks of fasting and did not recover after a week of refeeding. None of these components were affected by confinement stress. Plasma glucose in unstressed fish was generally unaffected by fasting or refeeding; however, plasma glucose increased after confinement stress in fed but not in fasted fish. The cortisol stress response was unaltered by fasting and remained robust. Plasma IGF-I generally decreased in fasted fish but was not significantly lower than fed fish until the fourth week. A week of refeeding did not restore plasma IGF-I concentrations. Plasma IGF-I concentrations were higher in confinement stressed fed fish after two and four weeks but were unchanged in the fourth week. There was no change in the plasma IGF-I concentrations in fasted or refed fish due to the stress. Liver weight and liver glycogen were essentially depleted after 2 weeks of fasting. The reduction of liver glycogen greatly reduced the glucose response to stress; however, the cortisol stress response was maintained for at least four weeks of fasting. Intraperitoneal fat was decreased very little after 4 weeks of fasting. Plasma IGF-I concentrations were reduced only after 3 weeks of fasting.     

Developmental changes in digestive physiology of nestling house sparrows, Passer domesticus

Six decades of studies have speculated that digestive capacity might limit avian growth rate or that developmental changes in the gut might determine developmental changes in digestive efficiency. However, there are no studies on digestive enzymes during avian development, except for studies on mainly domestic birds that exhibit the precocial mode of development. We studied alimentary organ masses, intestinal enzyme activities (sucrase, maltase, isomaltase, aminopeptidase-N), and pancreatic enzyme activities (amylase, trypsin, chymotrypsin) during development of a wild passerine bird exhibiting the altricial mode of development. Wild nestling house sparrows were studied immediately after removal from the nest (days 0, 3, 6 of age; day 0=hatch), whereas captives were raised in the laboratory beginning day 3 on a formulated casein/starch-based diet until fledging age (after day 12). Digestive biochemistry was dynamic. Tissue-specific activities of some digestive enzymes continued to increase through fledging, by >10 times in some cases (e.g., sucrase and maltase in midintestine). Total pancreatic amylase activity increased 100 times between hatch and day 12 through a combination of increases in tissue-specific activity and pancreas mass. House sparrows differ from poultry, in whom after about 2 wk of age the specific activity of intestinal and pancreatic digestive enzymes is generally constant or declines during development. The data on intestinal and pancreatic enzymes help explain why digestive efficiency of nestling house sparrows improves with age, and the data seem consistent with the idea that digestive capacity might limit feeding rate and hence growth rate.     

Effects of dietary supplementation with freshwater microalgae on growth performance,nutrient digestibility and gut health in weaned piglets

In pigs, digestive disorders associated with weaning lead to antibiotic use to maintain intestinal health. Microalgae have been studied in humans and rodents for their beneficial effects on health. The nutritional value of microalgae in animal diets has been assessed, but results were not conclusive. Dietary supplementation with microalgae as an alternative to antibiotic use was studied in two trials (72 piglets with initial BW=9.1±1.1 kg in trial 1 and 24 piglets with initial BW=9.1±0.9 kg in trial 2). All piglets were weaned at 28 days of age and then housed in individual cages. Piglets were randomly allocated to one of the four diets during 2 weeks after weaning: a standard diet with no supplementation (NC) or the standard diet supplemented with 1% Spirulina (SP), with 1% Chlorella (CV), or with 0.2% of colistin as positive control (PC). Trial 1 was performed to determine the effect of microalgae supplementation from 28 to 42 days on performance and incidence of diarrhoea. Animals received then a standard diet from 42 to 56 days of age. Trial 2 was performed from 28 to 42 days of age to assess nutrient digestibility of the experimental diets and to determine inflammatory status and intestinal morphology at 42 days of age. In trial 1, 94% of the pigs had diarrhoea in the 1st week after weaning with no beneficial effect of colistin on diarrhoea incidence, average daily feed intake (ADFI), average daily gain (ADG), and gain : feed (G : F) ratio. This suggests that the diarrhoea was due to digestive disorders that did not result from enterotoxigenic Escherichia coli infection. Supplementation with either Spirulina or Chlorella did not affect ADFI, ADG and G : F in trials 1 and 2 (P>0.10). Diarrhoea incidence was reduced in CV pigs compared with NC, SP and PC pigs (P<0.05). Total tract digestibility in pig receiving microalgae was greater for gross energy (P<0.05), and tended to be greater for dry matter, organic matter and NDF (P<0.10) compared with NC and PC pigs. Villus height at the jejunum was greater in SP and CV pigs compared with NC and PC pigs (P<0.05). This study shows a potential effect of both Spirulina and Chlorella supplementation on intestinal development and a potential of Chlorella supplementation to manage mild digestive disorders. Further investigation is necessary to determine the mechanism action of Spirulina and Chlorella on gut health and physiology.     

Topography of digestive enzymes in small intestine and activity of corresponding hydrolases in liver and kidney of adult pigs

Distribution of activities of disaccharidases (saccharase, maltase), amino- and dipeptidases, dipeptidyl peptidase IV (DPP) and alkaline phosphatase along the small intestine and of these hydrolases in liver and kidney, as well as distribution of the digestive enzyme activities between the membrane and cytosol fractions of enterocytes is characterized in adult 6-month old pigs. It has been shown that maximum of the studied enzyme activities, except for DPP, takes place in ileum. A higher level of the activities of the soluble form of saccharase, maltase, and aminopeptidase M and a less significant level of the activity of the glycyl-L-leucine dipeptidase soluble form in jejunum and ileum is found than those in rats and monkeys. The obtained data demonstrate the existence of the complex enzyme system in small intestine, liver, and kidney that participate in realization of nutritive and trophic-barrier functions.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 39–43.Original Russian Text Copyright © 2005 by Smirnova, Gordova, Timofeeva, Shcherbakov.     

Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA

To determine the mechanism of meal-regulated synthesis of pancreatic digestive enzymes, we studied the effect of fasting and refeeding on pancreatic protein synthesis, relative mRNA levels of digestive enzymes, and activation of the translational machinery. With the use of the flooding dose technique with L-[3H]phenylalanine, morning protein synthesis in the pancreas of Institute for Cancer Research mice fed ad libitum was 7.9 +/- 0.3 nmol phenylalanine.10 min(-1).mg protein(-1). Prior fasting for 18 h reduced total protein synthesis to 70 +/- 1.4% of this value. Refeeding for 2 h, during which the mice consumed 29% of their daily food intake, increased protein synthesis to 117.3 +/- 4.9% of the control level. Pancreatic mRNA levels of amylase, lipases, trypsins, chymotrypsin, elastases, as well as those for several housekeeping genes tested were not significantly changed after refeeding compared with fasted mice. By contrast, the major translational control pathway involving Akt, mTOR, and S6K was strongly regulated by fasting and refeeding. Fasting for 18 h decreased phosphorylation of ribosomal protein S6 to almost undetectable levels, and refeeding highly increased it. The most highly phosphorylated form of the eIF4E binding protein (4E-BP1) made up the 14.6% of total 4E-BP1 in normally fed animals, was only 2.8% after fasting, and was increased to 21.4% after refeeding. This was correlated with an increase in the formation of the eIF4E-eIF4G complex after refeeding. By contrast, feeding did not affect eIF2B activity. Thus food intake stimulates pancreatic protein synthesis and translational effectors without increasing digestive enzyme mRNA levels.