Influence of alcohol and sucrose consumption on energy balance and brown fat activity in the rat

Voluntary intake of solutions of alcohol (7%) and sucrose (10%) represented 20% and 25% of total metabolizable energy intake, respectively, in young male rats maintained on a stock diet, but total energy intake was similar to that of controls drinking water. Body weight and energy gains were similar for control and sucrose-treated rats but were significantly reduced in the group drinking alcohol, and energy expenditure, corrected for body size (kJ/kg0.75/day), was elevated in rats drinking alcohol (17% above control) or sucrose (18%). Gross and net energetic efficiencies were markedly depressed by consumption of alcohol but not by consumption of sucrose. Resting oxygen consumption, before and after injection of norepinephrine (25 micrograms/100 g body weight) was similar for all groups. Brown adipose tissue (BAT) mass and mitochondrial protein did not differ between groups, but the activity of the mitochondrial proton conductance pathway, assessed from the binding of 3H-guanosine diphosphate, was significantly elevated by alcohol and sucrose consumption. Thus, the increased energy expenditure associated with alcohol and sucrose ingestion may involve BAT thermogenesis, but this alone cannot explain the larger effects of alcohol on metabolic efficiency.     

Effects of age on diet-induced thermogenesis and brown adipose tissue metabolism in the rat

Measurements of energy balance, thermogenic responses to noradrenaline and brown adipose tissue (BAT) activity were performed in male Lister-hooded rats aged 3.5 and 6.5 months, and fed either a pelleted control diet or a palatable cafeteria diet for 15 d. Cafeteria feeding produced increases in energy intake of 34 and 30 per cent in 3.5 and 6.5-month-old rats respectively, and energy expenditure was elevated by 25 and 10 per cent in these groups. Three-and-a-half-month-old cafeteria-fed rats gained more energy than their controls, but net energetic efficiency was significantly reduced, while in the older cafeteria rats, body energy gain was markedly increased without any apparent effect on net efficiency. The thermogenic response to noradrenaline was enhanced by cafeteria feeding at both ages. The younger cafeteria-fed rats showed significant increases in the mass, protein content and mitochondrial yield of BAT, and the activity of the mitochondrial proton conductance pathway, assessed from GDP-binding, was greater than their controls. The 6.5-month-old cafeteria group also showed hypertrophy of BAT and small, but not significant, increases in the protein content of the tissue and mitochondrial GDP-binding. These results demonstrate that rats aged 3.5 months can exhibit diet-induced thermogenesis and activate BAT in response to overfeeding, but the capacity for thermogenesis declines with age and was virtually absent in 6.5-month-old rats.     

Energy balance and brown fat activity in rats fed cafeteria diets or high-fat, semisynthetic diets at several levels of intake

The object of the study was to determine the relative effects of hyperphagia and diet composition on energy balance and thermogenic activity in rats fed highly palatable cafeteria diets. Three types of diet were used: a pelleted stock diet, a cafeteria diet composed of a variety of human food items, and semisynthetic diets with nutrient compositions similar to the stock and cafeteria diets. Feeding rats a high-fat semisynthetic diet (similar to the cafeteria diet) at a energy intake equivalent to that of stock-fed controls (approximately 2.5 times maintenance) resulted in greater body energy gains and energetic efficiencies. These effects were probably due to the reduced energy costs of fat synthesis associated with high-fat diets. No effect of dietary composition on body energy gain was seen in animals fed below 2.5 times maintenance. Animals fed four cafeteria food items each day, or the high-fat semisynthetic diet, at 2.5 times maintenance showed significantly greater thermogenic responses to norepinephrine, increased brown adipose tissue (BAT) mass, and greater BAT mitochondrial GDP binding than controls on the same intake. Injection of propranolol reduced oxygen consumption in all groups, but the effect was greater in animals on higher intakes and was highest in the cafeteria groups. Thus, increasing fat intake, either by presenting cafeteria food items or by feeding a high-fat semisynthetic diet at the same level of intake as controls, stimulates the sympathetic nervous system and BAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brown adipose tissue activity and oxygen consumption after scald injury in the rat

Scald injury (30% surface scald) in the rat caused rapid (1-3 h) and transient decreases in oxygen consumption (VO2 20%), colonic temperature (1.1 degree C), and brown adipose tissue (BAT) thermogenic activity (22%). Three days after injury, VO2 was slightly increased in injured rats, and sympathetically mediated heat production (assessed from the inhibitory effect of a beta-adrenergic antagonist on VO2) was significantly greater than than for controls. At this time, BAT activity (in vitro mitochondrial GDP binding) was 35% higher in injured than control rats. Food intake was inhibited for only 24 h in injured animals, but weight gain was suppressed for at least 3 days. The data indicate that sympathetic modification of BAT thermogenesis may contribute to the changes in metabolic rate and body weight gain after scald injury in the rat.     

Effects of chronic low doses of d-fenfluramine on weight gain and calorie intake, brown adipose tissue thermogenic parameters and brain neurotransmitter content in rats fed chow or palatable diets

Male black-hooded rats of original age 3 months were maintained on either a standard laboratory chow diet or a palatable diet (32 animals in each group). After two months, when clear increases in weight gain and calorie intake in the latter group were evident, eight animals from each group were killed for analysis. For one further month, eight animals from each group received low doses (1-3 mg/kg/day) of d-fenfluramine in drinking water, another eight served as untreated controls, and the remaining eight were pair-fed to the treated groups. On killing, the interscapular brown adipose tissue (BAT) mass, and also BAT mitochondrial protein and uncoupling protein contents, and BAT mitochondrial cytochrome oxidase activity and GDP-binding were measured. Gross brain chemical changes were assessed by measuring whole brain contents of serotonin, noradrenaline and dopamine. The palatable diet produced clear increases in weight gain, calorie intake, total BAT mass, BAT mass with respect to body mass, total BAT mitochondrial protein and total amounts of uncoupling protein in each case; however, BAT mitochondrial protein per unit of BAT mass was not significantly increased, nor was the amount of uncoupling protein per mg of mitochondrial protein. Small, but variable, increases in brain neurotransmitter contents were observed. Drug-treated animals showed marked reductions in calorie intake and body weight compared to untreated controls but no significant decreases in body weight compared to pair-fed controls were evident. The pair-fed (i.e. 'slimming') groups displayed a decrease in BAT thermogenic parameters: d-fenfluramine partially prevented these decreases.     

Glucose uptake,glucose transporter GLUT4, and glycolytic enzymes in brown adipose tissue from rats adapted to a high-protein diet

In vivo rates of glucose uptake, insulin-responsive glucose transporter (GLUT4) content, and activities of glycolytic enzymes were determined in brown adipose tissue (BAT) from rats adapted to a high-protein, carbohydrate-free (HP) diet. Adaptation to the HP diet resulted in marked decreases in BAT glucose uptake and in GLUT4 content. Replacement of the HP diet by a balanced control diet for 24 hours restored BAT glucose uptake to levels above those in rats fed the control diet, with no changes in GLUT4 levels in 4 of 5 animals examined. BAT denervation of rats fed the control diet induced a 50% reduction in glucose uptake, but did not significantly affect the already markedly reduced BAT hexose uptake in HP diet-fed rats. It is suggested that the pronounced decrease in BAT glucose uptake in these animals is due to the combined effects of the HP diet-induced reductions in plasma insulin levels and in BAT sympathetic activity. Adaptation to the HP diet was accompanied by decreased activities of hexokinase, phosphofructo-1-kinase, and pyruvate kinase (PK). The activity of BAT PK in HP diet-fed rats was reduced to about 50% of controls, and approached normal levels 24 hours after diet reversion. BAT denervation induced a small (15%) decrease in BAT PK activity in control rats, but did not affect the activity of the enzyme in HP diet-adapted rats. Also, denervation did not interfere with the restoration of PK activity induced by diet substitution. Treatment with anti-insulin serum resulted in an almost 50% reduction in PK activity in both innervated and denervated BAT from rats fed the control diet, but caused a much smaller ( thick approximate 20%) decrease in BAT from HP diet-fed rats. Furthermore, anti-insulin serum administration completely suppressed the restoration of BAT PK activity induced by diet reversion. These data suggest that, differently from glucose uptake, BAT PK activity is predominantly controlled by hormonal/metabolic factors.     

Effect of cold acclimation on brown adipose tissue fatty acid synthesis in rats adapted to a high-protein, carbohydrate-free diet

The effect of cold acclimation on brown adipose tissue (BAT) fatty acid synthesis was investigated in rats adapted to a high-protein, carbohydrate-free diet. At an ambient temperature (25 degrees C), rates of fatty acid synthesis in BAT from rats adapted to the high-protein diet were reduced to 27% of rats fed the balanced diet and increased markedly after cold acclimation (10 days at 4 degrees C), although the increase was smaller than in control rats. BAT weight increase induced by cold acclimation was smaller in rats fed the high-protein diet (30%) than in controls (100%). When expressed per whole tissue, maximal activities of BAT glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate (ATP)-citrate lyase, and acetyl-coenzyme A carboxylase were markedly reduced in high-protein diet-adapted rats at 25 degrees C and increased after cold acclimation in BAT from the 2 groups. However, when expressed per milligram protein, only acetyl-coenzyme A carboxylase showed an increase in both controls and in rats fed the high-protein diet. G6P-dehydrogenase, malic enzyme, and ATP-citrate lyase increased (per milligram protein) only in rats adapted to the high-protein diet and actually decreased in BAT from cold-acclimated control rats. Initial (before activation) pyruvate dehydrogenase (PDH) complex activity was lower in BAT from rats fed the high-protein diet at 25 degrees C and increased in cold-acclimated rats from the 2 groups. Circulating levels of insulin decreased in the 2 groups after cold acclimation. The data suggest that the cold acclimation-induced increase in BAT lipogenesis in rats adapted to the high-protein diet was due to a restoration of sympathetic activity, which induced both BAT hyperplasia and activation of adipocyte free fatty acid (FFA) synthesis, with an important participation of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase.     

Serum lipids, lipoprotein composition and liver cholesterol in genetically obese Zucker rats fed semipurified diets containing either casein or soy protein

The effect of semipurified diets containing either casein or soy protein on serum lipids, lipoprotein composition and liver cholesterol was studied in genetically obese Zucker rats. The ingestion of a cholesterol-enriched semipurified diet containing casein resulted in elevated levels of serum cholesterol and phospholipids compared to the feeding of a soy protein diet. No differences in serum triglycerides were observed. Differences in serum cholesterol and phospholipids were mainly reflected in the very low density lipoproteins and low density lipoproteins and to a minor extent in the high density lipoproteins. Liver cholesterol paralleled the levels of cholesterol in the serum, the rats fed casein exhibited markedly higher levels of liver cholesterol than those fed soy protein. Furthermore, the rats fed casein also had enlarged livers. Thus, this study clearly shows the differential cholesterolemic effect of dietary casein and soy protein in genetically obese Zucker rats.     

Changes in body composition, brown adipose tissue activity and thermogenic capacity in BN/BiRij rats undergoing senescence

Metabolic rate, thermogenesis, brown adipose tissue (BAT) activity, and body composition were followed in ageing rats (female BN/BiRij) at 3 to 35.5 months of age. Colonic temperatures were similar in rats at 3 to 23 months of age (37.1–37.6°C), but significantly reduced (36.3°C) in those aged 36 months. Resting oxygen consumption (VO₂), corrected for body size, was comparable in all groups, but the thermogenic response to noradrenaline was significantly reduced with age. BAT mass was unaffected by age, but brown fat protein content, specific mitochondrial cytochrome oxidase activity and thermogenic activity (assessed from mitochondrial purine nucleotide binding) all declined markedly with age.

Carcass analysis revealed a fall in body protein in very old (35.5 month) rats, but body fat content increased up to 23 months of age and thereafter declined.     

Lipolysis and the antilipolytic effect of insulin in adipocytes from rats adapted to a high-protein diet

Free fatty acid (FFA) mobilization during fasting was investigated in rats fed a high-protein, carbohydrate-free (HP) diet (70% casein, 8% fat, wt/wt) or a balanced diet (66% carbohydrate, 17% casein, 8% fat) for 30 to 40 days. In vivo, rats on the HP diet showed reduced rates of plasma FFA increase during fasting. Their blood sugar remained unchanged and was higher than that of control rats 24 hours after removal of food. In the fed state, serum insulin levels were smaller in HP-fed rats but did not differ significantly in the two experimental groups during fasting. In vitro, the rates of glycerol and FFA release by epididymal fat pads obtained from fasted rats were similar in rats consuming the HP diet. Fat cells isolated from rats on the HP diet also had reduced rates of basal lipolysis. Furthermore, they showed a significant increase in responsiveness to the lipolytic action of noradrenaline and an increase in both sensitivity and responsiveness to the inhibitory effect of insulin on noradrenaline-stimulated lipolysis. Adipocytes from HP-fed and control rats had mean diameters of 51 and 60 mu, respectively, and estimated average volumes of 90 and 142 pL. On the basis of existing data on the correlation between size and lipolytic activity of fat cells, the smaller size of the adipocytes from HP-fed rats might account for the lower rate of basal lipolysis but not for the increased response to the hormones. The increased sensitivity of fat cells to the antilipolytic action of insulin may have been an important factor in the reduced lipomobilization during fasting in rats under the high-protein regimen.     

Influence of sodium intake on thermogenesis and brown adipose tissue in the rat

Presenting rats with a 0.9 per cent sodium chloride solution to drink instead of water had little or no effect on body weight gain and food intake, but resting oxygen consumption and total energy expenditure (corrected for body size) were elevated, and thermogenic responses to both noradrenaline and a meal were enhanced. Brown adipose tissue (BAT) mass and protein content were significantly elevated in saline treated rats, but mitochondrial GDP-binding capacity was depressed. Basal Na+, K+-ATPase activity was slightly increased in BAT homogenates from rats given saline, but noradrenaline-stimulated enzyme activity was much greater than control values. In rats drinking 1.8 per cent saline, energy intake, body weight gain and the efficiency of gain (g gain/MJ eaten) were all markedly depressed. BAT mass, corrected for differences in body size, was slightly greater than controls and the protein content of BAT was increased by 45 per cent. Rats allowed 0.9 per cent saline to drink for 7 d, and then presented with a palatable cafeteria diet, showed a more rapid rise in metabolic rate than cafeteria-fed animals drinking water. This difference was apparent only over the first 3-4 d of cafeteria feeding, and energy balance over 14 d was similar for both groups. These data show that increasing sodium intake with isotonic saline has very little effect on food intake or resting metabolic rate, but causes a marked increase in thermogenic capacity and responses to food or noradrenaline, probably because of an increase in active BAT mass. Changes in plasma ion concentrations or osmolarity, therefore, could be involved in the thermogenic response to food.     

Metabolic and hormonal investigations in long-term streptozotocin diabetic rats on different dietary regimens

Summary Groups of diabetic rats (65 mg/kg streptozotocin SC) were fed ad lib on three different dietary regimens for 43 weeks: a standard control diet (68% of calories as carbohydrate, 20% as protein, and 12% as fat), a low carbohydrate high protein diet (6% carbohydrate, 63% protein, 31% fat) or a low carbohydrate-high fat diet (5% carbohydrate, 75% fat, 20% protein). The high fat diet resulted in a fall of blood glucose from 700 to 350 mg/100 ml. Rats fed the high protein diet showed a similar initial decrease in blood glucose concentration, and a further improvement was evident from the 28th week on. After 43 weeks blood glucose levels were below 180 mg/100 ml and glycosuria below 100 mg/24 h in all rats fed the high protein diet. When rats exhibiting blood glucose levels below 180 mg/dl were transferred temporarily to standard diet blood glucose levels increased and marked glycosuria was observed. Rats on the standard diet maintained blood glucose concentrations greater than 500 mg/100 ml and glycosuria of about 16 g/24 h throughout the experiment. The pancreatic insulin content at death of rats fed the standard diet or the high fat diet was 1% of normal rats, whereas the values for the rats on the high protein diet were increased to 9%. Animals fed the low carbohydrate diets showed greater weight gain. In the high fat diet group there was a marked rise after 43 weeks in plasma triglycerides, free fatty acids, 3-hydroxybutyrate and acetoacetate in the plasma. Urea excretion was raised in the animals on the high protein diet. Thus, treatment with low carbohydrate diets for 10 months regardless of fat and protein content markedly improved the diabetic state of rats.     

Beneficial effects of low-carbohydrate-high-protein diets in long-term diabetic rats

Groups of streptozotocin-diabetic rats (65 mg/kg subcutaneously) were fed ad lib. on three different diets over 12 mo: a low-carbohydrate (CHO)-high-protein (6%:63% of calories) diet; a moderate-CHO-high-protein (27%:50%) diet; and a standard control diet (68% as CHO, 20% as protein). The 6%-CHO diet resulted in an initial decrease in nonfasting blood glucose from 550 to 280 mg/dl, followed by a further gradual improvement ending with blood glucose levels below 160 mg/dl and reduction of glycosuria to physiologic amounts. In the group fed the 27%-CHO diet, there was a similar initial decrease in blood glucose, but blood glucose values below 160 mg/dl after 12 mo were attained in only 3 of 8 rats. All rats fed the standard 68%-CHO diet maintained blood glucose levels between 500 and 650 mg/dl throughout. The late recovery in the low-CHO fed groups was associated with increased pancreatic insulin content. Animals fed low-CHO diets showed a better weight gain and improved general condition. The onset of cataracts as observed with the hand slit-lamp was regularly delayed in the animals on the 6%- and 27%-CHO diet; in some instances, it was entirely prevented. The threshold concentration of blood glucose seemingly required for onset of cataracts was about 300 mg/dl. Nerve sorbitol and fructose levels were clearly higher in hyperglycemic animals and correlated well with the severity of hyperglycemia. Thus, low-CHO-high-protein diets, which markedly improve hyperglycemia, may also improve at least some of the secondary changes usually seen in severely hyperglycemic rats.     

Stimulation of thermogenesis and brown fat activity in rats fed medium chain triglyceride

Gastric intubation of young male rats with 100 kJ/d of medium chain (C8 and C10) triglyceride (MCT) reduced their voluntary intake of stock diet such that total metabolizable energy intake was similar to that of rats intubated with water, and 41% of their energy intake was derived from MCT. Body weight, energy gain, and energetic efficiency were all markedly suppressed in MCT-fed rats, but energy expenditure over the 14-day experiment was significantly increased. Resting oxygen consumption, measured at thermoneutrality, was also enhanced in MCT-fed rats, but this difference was abolished by injection of the animals with the beta-adrenergic antagonist, propranolol. Brown adipose tissue mass was similar for both groups, but the activity of the mitochondrial proton conductance pathway, assessed from the binding of purine nucleotides, was increased by over 70%. These data indicate that the reduced weight gains of animals fed MCT are due to elevated rates of energy expenditure, possibly resulting from sympathetic activation of brown fat thermogenesis.     

Metabolic effects of medium- or long-chain triglycerides and high-protein, carbohydrate-free diets in Zucker rats

The effects of protein levels and types of fat in the diet on the metabolism of lean and obese Zucker rats were studied. For 40 days the rats were fed ad libitum one of four diets: two "usual protein" diets (19% protein by weight) with 19.4% triacylglycerols, either long chain (UP-LCT diet) or medium chain (UP-MCT diet); and two high protein (64% protein), carbohydrate-free diets, again with 19.4% triacylglycerols (HP-LCT and HP-MCT diets, respectively). The energy intakes of the obese rats decreased about equally on the HP-LCT, UP-MCT, and HP-MCT diets. The daily weight gain, which was high in the UP-LCT rats, was lower when carbohydrates were replaced by proteins, or when LCTs were replaced by MCTs; furthermore, when these two changes were made together, their beneficial effects on body weight were additive. The lipid gain, too, was high with the UP-LCT diet and lower both with the high protein diets and with the MCT diets; again combining the two amplified the two individual effects, so much that the final lipid concentration in the body was lowered, whereas the concentration of water increased. Hepatic acetyl CoA carboxylase activity was low when the diet supplied plenty of LCTs, but replacing carbohydrates with proteins in such a diet produced an additional decrease in this enzymatic activity. When either a normal protein or a high protein diet supplied MCTs in place of LCTs, acetyl CoA carboxylase activity was high and similar to that found with a high carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cafeteria feeding promotes diet-induced thermogenesis in monosodium glutamate-treated mice

We studied diet-induced thermogenesis (DIT) in cafeteria fed monosodium glutamate (MSG) and saline-treated mice. From 12 weeks of age MSG and saline-treated mice were fed a diet of either standard chow or a cafeteria diet of standard chow supplemented with chocolate or biscuits on alternate days for six weeks. There was a significant weight gain in cafeteria fed MSG-treated mice but not in cafeteria fed saline-treated mice. In cafeteria fed MSG-treated mice there was a significant increase in resting oxygen consumption. The response to exogenous norepinephrine was significantly increased in cafeteria fed saline-treated mice. The level of specific tritiated guanosine 5'-diphosphate binding to isolated mitochondrial fractions was significantly increased in both cafeteria fed MSG and saline-treated mice. It is concluded that (1) cafeteria feeding is capable of promoting DIT, within brown adipose tissue (BAT), in MSG-treated mice and (2) the mechanisms for the induction of thermoregulatory thermogenesis (TRT) and DIT are distinct since cold-induced TRT has previously been shown to be defective in MSG-treated mice.     

Relationship between magnesium and zinc levels of the diet and its protein utilization

Protein utilization of the diet was tested in relation to different levels of magnesium and zinc in rats. The experimental diets contained either a low (0.14 g Mg or 10 mg Zn/kg) or adequate (0.45 g Mg or 40 mg Zn/kg) level of Mg or Zn and two different quality protein sources: casein or wheat gluten. Net protein utilization and net protein radio indexes in case of casein were significantly lower for the diet containing a low level of Mg or Zn. For gluten diets, such differences were not observed. Digestibility of protein measured in rats fed a low Mg or Zn casein diet was the same as for the diets with an adequate content of these minerals. Rats fed low Mg or Zn casein diets showed a significantly lower plasma Mg or Zn and a lower liver DNA content in comparison to the rats on adequate Mg or Zn diets. The results indicate that the utilization of protein is affected by Mg and Zn content of the diet and that this relationship depends on the quality of protein.     

Energetic efficiency and brown adipose tissue uncoupling protein of obese Zucker rats fed high-carbohydrate and high-fat diets: the effects of adrenalectomy

The influence of diet on the response of lean and obese fa/fa rats to adrenalectomy has been studied. Adrenalectomized and sham-operated rats were fed either a semi-synthetic high-carbohydrate (HC) or high-fat (HF) diet for 13 days. Energetic efficiency, calculated for measurements of energy storage and energy intake, was increased in obese rats fed both HC and HF diets and reduced close to values of lean rats after adrenalectomy. Brown adipose tissue mitochondrial GDP binding and uncoupling protein concentration were reduced in control obese rats fed both HC and HF diets. After adrenalectomy the level of GDP binding and uncoupling protein concentration were increased to levels of lean rats. Molar ratios of GDP binding to uncoupling protein were similar in lean and obese rats, were unaffected by adrenalectomy, but were elevated in rats fed the HC diet (0.40 +/- 0.02 vs 0.28 +/- 0.03). The data suggests that diet, but not obese genotype, may influence the masking of mitochondrial uncoupling protein.     

Influence of Dietary Protein Concentration and Quality on Response to Erythropoietin in the Polycythaemic Rat

S ummary . The effects were examined of dietary protein concentration and quality on the response of polycythaemic hypertransfused rats to 6 units of human urinary erythropoietin. Rats were either starved or fed one of 14 different diets. Four protein sources were used, having a quality gradient from 100 to about 24. Two proteins—casein and wheat gluten—were used at five different levels of concentration (5–25%) in the diet. The response of rats maintained on the standard diet (Purina rat chow, 23.4% protein/g) was taken as the normal standard. The response to erythropoietin was 25% of normal in starved rats and 35% of normal in rats put on a protein-free diet. When 10% protein in the diet was obtained by using high biological value proteins (egg yolk or casein) the response to erythropoietin was normal. When the same concentration was achieved by using low biological value proteins (wheat gluten or corn protein) the response to erythropoietin was undistinguishable from that of rats put on the protein-free diet. When rats were maintained on diets with different concentrations of casein (5–25%) a normal response was observed when protein concentration was 10% with no further changes at higher concentrations. When rats were fed diets with different wheat gluten concentrations (5–25%) the response to erythropoietin was subnormal. These data suggest that the ability of rats to respond normally to erythropoietin is dependent on a continuous dietary intake of proteins at levels which are dependent on their biological values.     

Lack of effect of cerulein on pancreatic growth of rats fed a low-protein diet.

The effect of dietary protein deficiency and protein concentration of the diet on the pancreatic trophic response to a CCK analogue (cerulein) were studied. Rats were fed for 14 days with semipurified diets containing 5, 30, or 60% casein. During the final 4 days, they received 2 micrograms/kg cerulein or gelatin vehicle subcutaneously three times/day, and the effects on pancreatic weight and pancreatic content of protein, RNA, DNA, amylase, and chymotrypsin were determined. Cerulein failed to increase significantly any pancreatic parameter in rats fed 5% casein, while stimulating significant increases in almost all parameters in rats fed 30 and 60% casein diets. In the absence of cerulein treatment, increases in dietary protein levels caused progressive increases in all pancreatic growth parameters with the exception of amylase. In the presence of cerulein, increases in dietary protein concentrations caused progressive increases in pancreatic growth parameters (except amylase), which were maximal at 30% casein concentration of the diet for most parameters. The results confirm that pancreatic growth is stimulated by increasing protein concentration of the diet and indicate that a low protein diet, acting through a deficiency of dietary nitrogen and essential amino acids, limits the pancreatic trophic response to CCK or analogues. These results explain the failure of trypsin inhibitors to stimulate pancreatic growth in rats fed low levels of dietary protein.