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Biomedical subjects

J Peret

Publications and source records attributed to J Peret.

At least 19 recordsLinked to original sources

Metabolic changes during early starvation in rats fed a low-protein diet in the postweaning growth period.

Metabolic changes during the first 24 hours of starvation were studied in rats previously adapted for 3 weeks during the postweaning growth period to a low-protein diet using lactalbumin as a dietary protein source. Previous adaptation to a high-quality, low-protein diet reduced the effects of early starvation on the loss of body and liver weight. In rats fed a low-protein diet (6% lactalbumin, LP rats), free triiodothyronine (T3) concentration remained higher than in control rats (13% lactalbumin, C rats) throughout the experiment (+38%, 24 hours), and the plasma insulin concentration, which was lower than in C rats during the first 6 hours (-56%), was not different thereafter. Plasma insulin to glucagon molar ratio was lower (-54%) and liver cyclic adenosine monophosphate (cAMP) concentration was higher (+28%) in LP than in C rats in the fed state, but these were not different at 24 hours of starvation. Plasma glucose concentration was slightly lower in LP than in C rats (-15%) in the fed state, but it was not different in both groups during starvation. Whereas they were unchanged in the fed state, plasma lactate concentration was lower (-57%) and free fatty acid and total ketone body concentrations were higher (+38% and +183%, respectively) in LP than in C rats at 24 hours of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic effects in rats of a diet with a moderate level of medium-chain triglycerides.

Energy intake, weight gain, carcass composition, plasma fuels, hepatic metabolites and lipogenic enzyme activities were studied in adult rats fed either a low fat, high carbohydrate (LF) diet or one of two fat-containing diets in which 32% of the metabolizable energy was constituted by long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Compared with the LF diet, the MCT diet did not depress food and energy intake, weight gain, energy and nitrogen retention or lipid deposition and did not produce ketogenesis. The weight gain of rats fed LCT was 25% higher, and increased lipid deposition was observed. Lower lipogenic enzyme activities were observed in rats fed the LF diet containing 4% corn oil than in rats fed the MCT diet containing 1% corn oil. This effect disappeared when rats previously adapted to the LCT diet were fed LF or MCT diets containing 1% corn oil for 21 d. By d 21, in both groups, hepatic malic enzyme, ATP-citrate lyase, acetyl CoA carboxylase and fatty acid synthase activities were 2.2-, 2.0-, 2.3- and 1.8-fold higher than those of rats fed LCT. Intermediate hepatic glucose-6-phosphate dehydrogenase activities were observed in rats fed the MCT diet, compared with LCT (40% lower) and LF (1.6-fold higher) diets. These data show that in rats fed a diet in which MCT supplies 32% of metabolizable energy, a high activity of lipogenic enzymes is observed, suggesting that MCT had no inhibitory effect on the activity of these enzymes.

Animals↗

Metabolic changes in rats fed a low protein diet during post-weaning growth.

Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (-56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and +180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (-15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (-65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate.

Animals↗

Age-dependent glycolysis and gluconeogenesis enzyme activities in starved-refed rats.

Food intake, plasma glucose, insulin (I) and glucagon (G), hepatic glycogen and fructose 2,6-bisphosphate (F-2, 6-P2) and liver glucokinase, glucose 6-phosphatase (G6-Pase), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6-PF-2 kinase/F-2, 6-P2ase), pyruvate kinase (PK-L) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in 2 and 22-month-old rats before 3 d starvation and after 2, 4, 6, 24 and 48 h refeeding a high carbohydrate (HC, 74% w/w) diet. Expressed per 100 g of body weight, the food intake of old rats was 55% lower than that of young rats and the amount of carbohydrate absorbed hourly during the first 6 h of refeeding was 2.4-fold higher in young than in old rats. During the first 6 h of refeeding plasma glucose increased 2-fold and returned to normal values after 24 h in young rats, while plasma glucose did not change during refeeding in old rats. In young rats [I] fell by 85% after starvation and returned to normal values 2 h after refeeding. [I] was higher in old than in young rats; it decreased by 40% after starvation and returned to the basal value 4 h after refeeding. No marked changes were observed in plasma [G] in both groups. No difference was observed in hepatic glycogen in the two groups, while F-2, 6-P2 was higher in old than in young rats. In young rats, the opposite changes in liver glucokinase and G6-Pase activities occurring after starvation and during refeeding were

Aging↗

Effects of long-term feeding of high-protein or high-fat diets on the response to exercise in the rat.

The aim of this work was to find by which mechanisms an increased availability of plasma free fatty acids (FFA) reduced carbohydrate utilization during exercise. Rats were fed high-protein medium-chain triglycerides (MCT), high-protein long-chain triglycerides (LCT), carbohydrate (CHO) or high-protein low-fat (HP) diets for 5 weeks, and liver and muscle glycogen, gluconeogenesis and FFA oxidation were studied in rested and trained runner rats. In the rested state the hepatic glycogen store was decreased by fat and protein feeding, whereas soleus muscle glycogen concentration was only affected by high-protein diets. The percentage decrease in liver and muscle glycogen stores, after running, was similar in fat-fed, high-protein and CHO-fed rats. The fact that plasma glucose did not drastically change during exercise could be explained by a stimulation of hepatic gluconeogenesis: the activity of phosphoenolpyruvate carboxykinase (PEPCK) and liver phosphoenolpyruvate (PEP) concentration increased as well as cyclic adenosine monophosphate (AMPc) while liver fructose 2,6-bisphosphate decreased and plasma FFA rose. In contrast, the stimulation of gluconeogenesis in rested HP-, MCT- and LCT-fed rats appears to be independent of cyclic AMP.

Animals↗

Post-exercise glycogen resynthesis in trained high-protein or high-fat-fed rats after glucose feeding.

This study examined the effect on glycogen resynthesis during recovery from exercise of feeding glucose orally to physically trained rats which had been fed for 5 weeks on high-protein low fat (HP), high-protein/long-chain triglyceride (LCT) or high carbohydrate (CHO) diets. Muscle glycogen remained low and hepatic gluconeogenesis was stimulated by long-term fat or high-protein diets. The trained rats received, via a stomach tube, 3 ml of a 34% glucose solution immediately after exercise (2 h at 20 m.min-1), followed by 1-ml portions at hourly intervals until the end of the experiments. When fed glucose soleus muscle glycogen overcompensation occurred rapidly in the rats fed all three diets following prolonged exercise. In LCT- and CHO-fed rats, glucose feeding appeared more effective for soleus muscle repletion than in HP-fed rats. The liver demonstrated no appreciable glycogen overcompensation. A complete restoration of liver glycogen occurred within a 2- to 4-h recovery period in the rats fed HP-diet, while the liver glycogen store had been restored by only 67% in CHO-fed rats and 84% in LCT-fed rats within a 6-h recovery period. This coincides with low gluconeogenesis efficiency in these animals.

Animals↗

Fatty acid metabolism in hepatocytes isolated from rats adapted to high-fat diets containing long- or medium-chain triacylglycerols.

Fatty acid oxidation and synthesis were studied in isolated hepatocytes from adult rats adapted for 44 days on low-fat, high-carbohydrate (LF), diet or high-fat diets, composed of long-chain (LCT) or medium-chain (MCT) triacylglycerols. The rates of [1-14C]octanoate oxidation were almost similar in each group studied, whereas the oxidation of [1-14C]oleate was 50% lower in the LF group than in animals adapted to high-fat diets. The rates of oleate oxidation are inversely correlated with the rates of lipogenesis. However, it seems unlikely that [malonyl-CoA] itself represents the sole mechanism involved in the regulation of oleate oxidation during long-term LCT or MCT feeding, since: (1) despite a 3-fold higher concentration of malonyl-CoA in MCT-fed rats than in LCT-fed ones, the rates of oleate oxidation are similar; (2) when malonyl-CoA concentration is increased after stimulation of lipogenesis (by adding lactate + pyruvate) in MCT-fed rats, to a level comparable with that of the LF group, the rate of oleate oxidation remains 55% higher than that measured under similar conditions in the LF-fed rats; (3) in the LF group, the 90% decrease in malonyl-CoA concentration [by 5-(tetradecyloxy)-2-furoic acid] is not associated with a stimulation of oleate oxidation. By contrast, the sensitivity of carnitine palmitoyltransferase I (CPT I) to malonyl-CoA is markedly decreased in the LCT- and MCT-fed rats, by 90% and 70% respectively. The relevance of this decrease in the sensitivity of CPT I is discussed.

Animals↗

Effects of ingestion of high protein or excess methionine diets by rats for two years.

Eighteen male Wistar rats weighing 230 g (9 wk old) were fed casein diets containing 10% protein (HC), 50% protein (HP) or 10% protein plus 2% DL-methionine (MET) for 2 yr. In HC rats, mean body weight was 570 g; the carcass contained 13.5% protein and 37% lipid. The HP-fed rats had a 100 g lower body weight than HC rats due solely to a smaller amount of body lipid. Liver urea concentration and kidney weight were higher in HP rats than in HC rats. The body weight of MET-fed rats was lower than the other two groups and body lipid was only 30% that of HC rats. Histologic examination showed a normal aspect of the thoracic aorta from HC rats, whereas in HP, moderate signs of vascular aging--thicker intima and media with hypertrophy of smooth muscular cells (smc) with collagen enrichment and diffuse fibrosis--were observed. Aortas from MET rats also exhibited thicker intima and media due to smc hypertrophy. Some smc presented degenerative aspects and necrosis; other smc were replaced by chondroid cells and foci of fibrosis, resulting in a loss of the distension capacity of the aorta. Such an advanced stage of vascular aging is not normally found in 2-yr-old rats.

Aging↗

[Long-term consumption of a diet with moderate medium chain triglyceride content does not inhibit the activity of enzymes involved in hepatic lipogenesis in the rat].

The activities of glucose 6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40), ATP-citrate lyase (EC 4.1.3.8), acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthetase were lower (-25 to -60%) in liver of rats fed during 45 days with a moderate long-chain triglycerides (LCT) content diet (32% of metabolizable energy, ME), than in control rats fed with a low fat diet (LCT, 10% of ME). However, the fall in malic enzyme activity was not significant. In contrast, these activities were higher (+40 to +160%) in rats fed with a diet with a moderate medium-chain triglycerides (MCT) content (32% of ME), than in control rats. Nevertheless, the increase in activity of malic enzyme and ATP-citrate lyase was more important. Contrary to LCTs, MCTs had no inhibitory effect on the activity of enzymes involved in hepatic lipogenesis.

ATP Citrate (pro-S)-Lyase↗

Metabolic effects induced by long-term feeding of medium-chain triglycerides in the rat.

Energy intake, weight gain, carcass composition, plasma hormones and fuels, hepatic metabolites and the activities of phosphoenolpyruvate carboxykinase (PEPCK), malic enzyme, and glucose 6-phosphate dehydrogenase (G6P-DH) were examined in adult rats during a 44-day period of low fat, high carbohydrate (LF) feeding or of consumption of one or two high (70% metabolizable energy) fat diets composed of 63% (metabolizable energy) long-chain (LCT) or medium-chain (MCT) triglycerides. Energy intake was similar in the LCT and MCT groups but was less than that of LF group. The weight gain of rats fed MCT diet was 30% less than that of rats fed LF or LCT diets. Energy retention was less when the diet provided MCT than LCT or LF, and that resulted in a 60% decrease in the daily lipids deposition. Plasma glucose, free fatty acids, glycerol, and insulin/glucagon ratio were similar in the three groups. Blood ketone body (KB) concentrations in rats fed the high fat diets were extremely elevated, particularly in the MCT group, but declined throughout the experiment and by the 44th day hyperketonemia decreased by 50% but remained higher than in the LF diet. The blood beta-hydroxybutyrate/acetoacetate (B/A) ratio remained slightly elevated in rats fed the high fat diets. Similar changes were observed in liver KB concentration and in the B/A ratio. Liver lactate/pyruvate ratio elevated in the LCT and MCT groups at the initiation of the diets decreased by 50% at the end of the experiment. The consumption of high fat diets led to a 1.5-fold increase in liver PEPCK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of gluconeogenesis from various precursors in isolated rat hepatocytes during starvation or after feeding a high protein, carbohydrate-free diet.

Gluconeogenesis from dihydroxyacetone (DHA), glycerol, lactate, pyruvate or alanine was studied in the absence or in the presence of glucagon in hepatocytes isolated from starved rats or from rats fed a high protein diet for 2-48 h. In both groups, gluconeogenesis from DHA, glycerol, lactate and pyruvate exhibited similar changes over 48 h; the rates of glucose production increased progressively until 24 h and then plateaued. During the early phase (2-11 h), gluconeogenesis from DHA and glycerol were higher than gluconeogenesis from lactate and pyruvate. During the first 24 h of the experiment, gluconeogenesis from alanine displays a kinetic similar to that from lactate or pyruvate. After feeding a high protein diet for 24 to 48 h, gluconeogenesis from alanine was slightly higher than that in starved rats and paralleled the increase in alanine aminotransferase activity. Glucagon stimulated gluconeogenesis from DHA up to 48 h, but with glycerol this effect occurred only during the early phase (2-11 h). Glucagon stimulated gluconeogenesis from lactate, pyruvate or alanine by 1.35-fold throughout the experimental period. These findings suggest that the development of gluconeogenesis during starvation or after feeding a high protein diet displays different kinetics, depending on the substrate used and on the level of entry in the gluconeogenic pathway: triose phosphates or pyruvate.

Animals↗

Studies on the early changes in rat hepatic fructose 2,6-bisphosphate and enzymes in response to a high protein diet.

Pertinent hepatic metabolites and enzymes were examined in rats fed a high carbohydrate (HC) diet and during the first 24 h of either starvation or feeding a high protein (HP) diet. Consumption of the HC diet induced slight but definite 24-h oscillations in hepatic concentrations of cyclic AMP, glycogen, glucose 6-phosphate, fructose 2,6-bisphosphate, fructose 1,6-bisphosphate and phosphoenolpyruvate, as well as the activities of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The transition to starvation or the HP diet induced, within 12 h, concurrent increases in cyclic AMP and phosphoenolpyruvate and decreases in glycogen, glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate and fructose 1,6-bisphosphate. These changes were associated with a decrease in the ratio of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and an increase in phosphoenolpyruvate carboxykinase. These results suggest that the activity of the fructose 6-phosphate/fructose 1,6-bisphosphate cycle is similar during the first 24 h of starvation or HP consumption.

Analysis of Variance↗

Comparison between starvation and consumption of a high protein diet: plasma insulin and glucagon and hepatic activities of gluconeogenic enzymes during the first 24 hours.

Plasma insulin, glucagon, glucose, free fatty acids and glycerol, hepatic cyclic AMP and glycogen, and liver phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase) and alanine amino transferase (AAT) activities were examined in adult rats during the first 24 h of either starvation or consumption of a high protein, carbohydrate-free (HP) diet. Under both nutritional conditions, plasma insulin fell within 12 h and remained constant thereafter. Glucagon increased 12 h after the start of the experiment and peaked between 18-24 h. The insulin: glucagon ratio was lower during the last 12 h of the experiment. In both experimental groups, liver cyclic AMP increased progressively and peaked between 15-24 h, but it increase was higher on HP diet than on starvation. Whereas plasma glucose remained low on starvation for 24 h, it returned to normal on consumption of the HP diet. In both groups, liver glycogen fell within 12 h and remained low until the end of experiment. FBPase, G6Pase and AAT did not change on starvation, while they increased toward the end of 1 d HP consumption. During starvation or consumption of the HP diet, PEPCK increased progressively and peaked between 15-24 h, but the increase was greater with the HP diet than with starvation. These findings suggest that in the first 24 hours, the adaptative response of hepatic gluconeogenesis is higher with a HP diet than upon starvation.

Adaptation, Physiological↗

Comparison between starvation and consumption of a high protein diet in rats: hepatic metabolites and amino acid levels during the first 24 hours.

Changes in hepatic levels of lactate, pyruvate, phosphoenolpyruvate, alpha-ketoglutarate, malate, oxaloacetate, adenine nucleotides, inorganic phosphate, ketone bodies, alanine, serine, glycine, aspartate, glutamate, valine and urea were examined in adult rats during the first 24 h of either starvation or consumption of a high protein (HP) diet. No differences were found between these two conditions in the concentration of metabolites studied or the cytosolic redox state. Under both conditions, the cytosolic phosphorylation state decreased to a low 15 h into the experiment but the changes were more pronounced on the HP diet. Hepatic ketone bodies rose sharply after 12 h, with the increase 2.5 times greater for starved rats. In starvation, hepatic aspartate, valine, and urea were low and glycine was high, whereas the opposite was seen for the HP diet. In both groups, alanine fell within 9 h and remained low thereafter. These findings suggest that, in the first 24 h of starvation, the energy necessary for gluconeogenesis is obtained from fatty acid oxidation, while during HP feeding the energy for both gluconeogenesis and ureagenesis are derived from fatty acid oxidation and amino acid oxidation.

Adenine Nucleotides↗

Effect of intragastric triglyceride administration on glucose homeostasis in newborn pigs.

The fasting hypoglycemia (1.78 +/- 0.29 mmol/l) which develops in 48-h-old pigs is partially reversed (3.85 +/- 0.55 mmol/l) after gastric administration of long-chain triglycerides (LCT). The increase in blood glucose induced by LCT feeding was not secondary to a decreased glucose utilization because glucose disappearance rate increased in LCT-fed piglets but resulted from a twofold increase in glucose appearance. By using the crossover-plot technique, the stimulation of hepatic gluconeogenesis induced by LCT feeding has been localized at 1) the level of pyruvate carboxylase owing to the twofold increase in hepatic acetyl-CoA concentration and 2) the level of glyceraldehyde-3-phosphate dehydrogenase secondary to the increase in reducing equivalents (NADH), which displaces this equilibrium reaction in the direction of gluconeogenesis. As blood lactate, pyruvate, and alanine concentrations increased after LCT feeding, the possible effects of LCT on pyruvate dehydrogenase in peripheral tissues are discussed. These data demonstrate that fatty acids stimulate hepatic gluconeogenesis in 48-h-old fasting piglets and underline the role of fat provision in the regulation of glucose homeostasis during the neonatal period in the pig.

Animals↗

Separate effects of fatty acid oxidation and glucagon on gluconeogenesis in isolated hepatocytes from newborn pigs.

In hepatocytes isolated from 48-hour-old suckling pigs, the inhibition of endogenous fatty acid oxidation leads to a 30% inhibition of glucose production from lactate. Addition of oleate plus carnitine to hepatocytes from 48-hour-old fasting pigs increases by 30% the rate of gluconeogenesis from lactate. In hepatocytes isolated from fasting newborn pigs, addition of glucagon (0.5 ng/ml) produces a 30% increase in the rate of glucose production from lactate and a 70% increase of glucose synthesis from dihydroxyacetone. The high rate of lactate plus pyruvate production in fasting piglets is markedly suppressed by glucagon and return to the value measured in suckling newborns. Combined addition of oleate and glucagon to hepatocytes from fasting piglets increases by 2-fold the rate of glucose production from lactate but does not restore totally the rate of glucose synthesis found in suckling piglets. It is concluded that fatty acid oxidation and hormonal environment contribute significantly to the development of an active gluconeogenesis in the newborn pig but do not represent the sole factors involved in the regulation of hepatic gluconeogenesis.

Animals↗

Development of gluconeogenesis from dihydroxyacetone in rat hepatocytes during a feeding cycle and starvation.

Pyruvate kinase activity and the rates of gluconeogenesis and glycolysis in rat hepatocytes were evaluated by production of glucose and lactate + pyruvate from dihydroxyacetone during a feeding cycle or progressive starvation. In fed rats, during daylight (low food intake) and until darkness, gluconeogenesis progressively increased and glycolysis decreased slightly, but gluconeogenesis never exceeded glycolysis. During nocturnal feeding, gluconeogenesis and glycolysis returned to their morning rates. After 8 h starvation, an equal proportion of dihydroxyacetone was converted into glucose and into lactate + pyruvate. When glycogen was depleted (11 h of starvation), gluconeogenesis was maximal and glycolysis minimal. In fed and starved rats, the concentration of fructose 1,6-bisphosphate was the same. The activity ratio of pyruvate kinase (ratio of velocity at 0.5 mM-phosphoenolpyruvate to the maximum catalytic activity obtained with 4mM-phosphoenolpyruvate) was high in crude extracts of cells incubated with dihydroxyacetone and low in (NH4)2SO4-treated extracts, but remained unchanged during the whole experiment. There was no correlation between the rates of gluconeogenesis and glycolysis from dihydroxyacetone and the activity ratio of pyruvate kinase.

Animals↗

Metabolic effects of high-protein diets in Zucker rats.

The effects of dietary protein on the metabolism of proteins, carbohydrates, and especially, lipids were investigated in genetically obese Zucker rats and their lean siblings. For 40 days the rats received diets containing 15%, 64%, or 82% protein, included at the expense of cornstarch. In the obese animals, the high-protein diets led to decreased food intake and weight gain. While these diets decreased the activities of lipogenic enzymes along with the lipid gain, they did not decrease the final body-fat content. The increase protein intake stimulated hepatic ureogenesis and gluconeogenesis. Lipolysis was stimulated, as demonstrated by an accumulation of ketone bodies in the liver. Blood levels of triacylglycerols, free glycerol, and nonesterified fatty acids were concomitantly decreased, which suggests an accelerated turnover of lipids. Whatever the composition of the diet, total energy retention of the lean rats was always less than that of the obese rats. The changes observed on high-protein diets were essentially the same for the two groups, except that the final body-content of lipids in the lean rats was significantly lower. In the absence of exogenous carbohydrate, the lean rats were barely able to retain nitrogen and to maintain hepatic lipogenesis. Unlike the rats from other strains, the lean Zucker rats could not adapt to a low-carbohydrate diet; this failure may be due to a metabolic disorder.

Acetyl-CoA Carboxylase↗