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J Peret

Publications and source records attributed to J Peret.

At least 37 records · Page 2Linked to original sources

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)

Adenine Nucleotides↗

Glucose turnover and recycling in unrestrained and unanesthetized 48-h-old fasting or post-absorptive newborn pigs.

The metabolism of glucose has been studied in 48-h-old unanesthetized fasting and post-absorptive sucking piglets. Both [6-3H]- and [U-14C]glucose were administered either by a single injection method or by a primed infusion technique. The rates of glucose turnover and recycling were estimated under steady-state conditions. The rates of glucose turnover and recycling in 48-h-old fasting or post-absorptive piglets were not statistically different when measured using the single injection technique or the primed infusion method. The mean (with SE) rate of glucose turnover was 65.8 (2.5) in post-absorptive and 31.1 (1.9) mumol/kg per min in fasted newborn pigs. Glucose utilization was linearly related to blood glucose concentration; regression analysis indicated a y-intercept of 7.2 mumol/kg per min. As tested by arterio-portal differences the gut was not releasing glucose or galactose in 5 h-post-absorptive sucking newborn pigs. Thus, the higher rates of glucose turnover in post-absorptive newborn pigs compared with fasting ones suggest that hepatic glucose production is enhanced in post-absorptive sucking piglets. The mean (with SE) rates of glucose recycling were four times higher in post-absorptive piglets than in fasting ones, i.e. 14.4 (1.6) and 3.7 (0.5)% of [6-3H]glucose turnover respectively. As liver glycogen was exhausted in 48-h-old sucking piglets, this suggests that hepatic glucose production results from gluconeogenesis.

Animals↗

Gluconeogenesis from dihydroxyacetone in rat hepatocytes during the shift from a low protein, high carbohydrate to a high protein, carbohydrate-free diet.

Pyruvate kinase activity and rates of gluconeogenesis and glycolysis in rat hepatocytes were evaluated by production of glucose and lactate + pyruvate from dihydroxyacetone during the first 48 hours after the shift from a low protein, high carbohydrate diet to a high protein, carbohydrate-free diet. The effect of glucagon was also studied. In the absence of glucagon, 11-17 hours after the dietary shift when glycogen was lowest, gluconeogenesis was maximal and glycolysis minimal. The concentration of fructose 1,6-biphosphate was high and did not change during the experiment. The activity ratio of pyruvate kinase measured with phosphoenolpyruvate (PEP) (V0.5 mM PEP/V4 mM PEP) was high in crude extracts and low in (NH4)2SO4-treated extracts, but remained unchanged during the whole experiment. There was no correlation of the rates of gluconeogenesis or glycolysis from dihydroxyacetone with the activity ratio of pyruvate kinase. With glucagon, gluconeogenesis from dihydroxyacetone was increased and a concurrent decrease in glycolysis was paralleled with a decrease in the fructose 1,6-bisphosphate concentration and in the activity ratio of pyruvate kinase. The activity ratio of pyruvate kinase in (NH4)2SO4-treated cells represented about 50% of that in the absence of the hormone. This difference may be related to glucagon-induced phosphorylation of pyruvate kinase.

Animals↗

Pyruvate kinase activity in isolated rat hepatocytes during a feeding cycle and during fasting.

The short-term regulation of pyruvate kinase in rat hepatocytes was studied during a feeding cycle or progressive fasting. In fed and fasted rats, the activity ratio of pyruvate kinase (V0.5-mMPEP/Vmax) in crude extracts was directly correlated with the concentration of glucose 1,6-bisphosphate++ in hepatocytes. Precipitation of the enzyme from homogenates with ammonium sulphate, which removes fructose 1,6-bisphosphate, induced in both groups of animals a low activity ratio of pyruvate kinase which remained unchanged during the whole experiment. These results show that in absence of added glucagon in hepatocytes, the activity of pyruvate kinase is mainly controlled by the intracellular level of fructose 1,6-bisphosphate. Addition of glucagon to hepatocytes from fed or fasted rats inactivated pyruvate kinase and decreased the concentration of fructose 1,6-bisphosphate in cells. However, in crude extracts both the activity ratio of pyruvate kinase and fructose 1,6-biphosphate levels were higher in fed rats than in starved rats. These findings suggest that glucagon-induced inactivation of pyruvate kinase also depends upon the concentration of fructose 1,6-biphosphate in hepatocytes.

Animals↗

Metabolic fate of non-esterified fatty acids in isolated hepatocytes from newborn and young pigs. Evidence for a limited capacity for oxidation and increased capacity for esterification.

In hepatocytes isolated from 48 h-old starved of suckling newborn pigs or from 15-day-old starved piglets, the rate of ketogenesis from oleate or from octanoate is very low. This is not due to an inappropriate fatty acid uptake by the isolated liver cells, but results from a limited capacity for fatty acid oxidation. Some 80-95% of oleate taken up is converted into esterified fats, whatever the age or the nutritional conditions. Three lines of indirect evidences suggest that fatty acid oxidation is not controlled primarily by malonyl-CoA concentration in newborn pig liver. Firstly, the addition of glucagon does not increase fatty acid oxidation or ketogenesis. Secondly, the rate of lipogenesis is very low in isolated hepatocytes from newborn pigs. Thirdly, the rates of oxidation and ketogenesis from octanoate are also decreased in isolated hepatocytes from newborn and young piglets. The huge rate of esterification of fatty acids in the liver of the newborn pigs probably represents a species-specific difference in intrahepatic fatty acid metabolism.

Age Factors↗

Effects of excess methionine ingestion on hepatic phosphate, adenine nucleotides and free amino acids in the rat.

Adult male rats were force-fed either a single dose of 200 mg of DL-methionine or an amino acid mixture with the pattern of casein. The animals were anesthetized with pentobarbital at 0, 1.5, 3 and 4 hours after intubation, and samples of liver were removed by a freeze-clamping technique at 0, 15 and 30 seconds of ischemia. Hepatic ATP, ADP, AMP, Pi, glucose-6-phosphate, glucose and certain nitrogenous compounds as well as plasma glucose were determined. After methionine was given by intubation, hepatic methionine and glutathione increased severalfold within 1.5 hours; cystathionine showed a transient rise at this time but returned to normal at 3 and 4 hours, when taurine was progressively increasing. Several nonessential amino acids decreased, suggesting that they may be utilized for energy. Methionine force-feeding did not modify the concentration of hepatic adenine nucleotides and probably did not change their turnover, as estimated from changes during ischemia. The level and production of Pi during ischemia was increased however. After force-feeding the amino acid mixture, hepatic methionine, cystathionine and taurine were unaffected, and glutathione increased only at hours 3 and 4; glycine and threonine were elevated by 1.5 hours. Hepatic adenine nucleotides, inorganic phosphate and glucose were not significantly affected by the feeding of amino acids by intubation.

Adenine Nucleotides↗

Development of gluconeogenesis in isolated hepatocytes from fasting or suckling newborn pigs.

The rates of glucose production from various substrates were investigated in isolated hepatocytes from fasting and suckling newborn pigs from birth to 48 hours of life. They were quantitatively compared to the rate of glucose production measured in 15-day-old suckling and fasting piglets. The data indicate that the rates of gluconeogenesis from each gluconeogenic precursor (lactate, pyruvate, alanine, glycerol, dihydroxyacetone and galactose) were two- to threefold higher in suckling than in fasting newborn pigs. The rates of glucose production from various gluconeogenic precursors were similar in suckling newborn pigs and in 15-day-old fasting piglets. The difference in the capacity for gluconeogenesis in isolated hepatocytes from fasting and suckling newborn pigs could explain why hypoglycemia develops during fasting in newborn pigs whereas suckling neonates remain normoglycemic.

Animal Population Groups↗

Hepatic metabolites and amino acid levels during adaptation of rats to a high protein, carbohydrate-free diet.

Changes in hepatic levels of lactate, pyruvate, phosphoenolpyruvate (PEP), alpha-ketoglutarate, malate, oxaloacetate, ketone bodies, alanine, serine, glycine, aspartate, glutamate, glutamine, valine, urea, adenine nucleotides and inorganic phosphate were examined in rats consuming a high protein, carbohydrate-free diet for up to 40 days. While some components showed transient changes, others (pyruvate, malate, oxaloacetate, PEP, ketone bodies, alanine, glycine, glutamine, valine, urea, adenine nucleotides and inorganic phosphate) were permanently altered. The cytoplasmic and mitochondrial redox states were only transiently affected and by day 24 were not different from control values. In contrast, the cytoplasmic phosphorylation state was affected from day 1 on; this suggests a role for the latter in permanently reorienting metabolism toward gluconeogenesis and ureogenesis.

Adaptation, Physiological↗

Circadian variation of liver metabolites and amino acids in rats adapted to a high protein, carbohydrate-free diet.

Diurnal variation in hepatic levels of lactate, pyruvate, phosphoenolpyruvate (PEP), alpha-ketoglutarate, malate, oxaloacetate, ketone bodies, alanine, serine, glycine, aspartate, glutamate, glutamine, valine, urea, adenine nucleotides and inorganic phosphate were studied in rats adapted to a high protein, carbohydrate-free diet for 24 days. Most circadian rhythms differed in relation to controls (10% protein diet); many merely had different amplitudes, some were inverted, and some exhibited drastically altered patterns. Cytoplasmic redox state exhibited nearly similar variations and phosphorylation state differed primarily in amplitude whereas mitochondrial redox state was highly depressed in the absorptive phase. The metabolic regulation implied by the results is discussed in relation to both circadian variations of plasma insulin and glucagon concentrations, and pyruvate kinase and phosphoenolpyruvate carboxykinase activities previously reported.

Adenine Nucleotides↗

Plasma glucagon and insulin concentrations and hepatic phosphoenolpyruvate carboxykinase and pyruvate kinase activities during and upon adaptation of rats to a high protein diet.

Plasma hormones, glucose and free fatty acids, liver glycogen and two key enzymes of glycolysis and gluconeogenesis were examined in adult rats during a 40-day period of high protein feeding. Plasma insulin fell within 1 day but returned to normal after 4 days. Glucagon changed more slowly, reaching a maximum on day 4 and declined to near the control value within 24 days. Consequently, the insulin to glucagon ratio was lower on days 1, 4 and 8 and was nearly normal on day 24. With respect to hepatic enzymes, phosphoenolpyruvate carboxykinase activity rose sharply on the 1st day and remained elevated for 40-day period; the L-isozyme of pyruvate kinase, although unchanged on the 1st day, decreased thereafter and from day 8 on represented 15--20% of control. Circadian variations in these parameters were also measured in rats adapted to the high protein diet. In such animals, the diurnal change in plasma hormones was less marked but tended to be inverted with respect to controls; the insulin/glucagon ratio was highest during daylight on high protein and in late night on the control diet. Over 24 hours, pyruvate kinase activity was related directly and phosphoenolpyruvate carboxykinase inversely to the hormone ratio. We concluded that in rats adapted to high protein, as in controls, the diurnal balance between glycolysis and gluconeogenesis is probably regulated by the same factor, namely the insulin/glucagon ratio.

Animals↗

Changes in circulating fuels, pancreatic hormones and liver glycogen concentration in fasting or suckling newborn pigs.

The effect of fasting or suckling on blood glucose, circulating fuels, pancreatic hormones and liver glycogen concentration have been measured in newborn pigs during the first 48 h of life. Blood glucose concentrations fell to hypoglycaemic values after 48 h of fasting whereas for the same period of time, suckling piglets maintain a normal blood glucose. These differences are not due to hepatic glycogen mobilization, since liver is totally depleted from its high glycogen stores 24 h after birth, both in fasting and suckling piglets. Blood lactate is present at a high concentration during the first 48 h, both in fasting and suckling piglets. In contrast, blood pyruvate concentration is lower in suckling than in fasting newborn pigs. Colostrum intake leads to an increase in blood amino acid concentrations in the suckling piglets in comparison with the fasting newborn. Plasma non-esterified fatty acid levels and blood glycerol concentrations are lower in fasting piglets than in the suckling ones. In suckling newborn pigs, circulating ketone bodies are very low despite the increase in non-esterified fatty acids levels. The decrease in plasma insulin/glucagon molar ratio at birth, is due to a decrease in plasma insulin and an increase in plasma glucagon, both in fasting and suckling piglets. Plasma insulin and glucagon concentrations are higher during suckling than during fasting. The data suggest that gluconeogenesis could be impaired, in fasting newborn pigs, by a low plasma glucagon level and/or a limiting availability of non-esterified fatty acids.

Amino Acids↗

Development of gluconeogenic enzymes in the liver of fasting or suckling newborn pigs.

Gluconeogenic enzymes and substrates were measured in the livers of fasted and suckled newborn pigs in the first 48 h postpartum. The activities at birth of glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase were, respectively, 70%, 45%, 117% and 35% of adult values. At birth, cytosolic phosphoenolpyruvate carboxykinase represented 35% of total activity, a similar distribution to that in the adult. In suckled piglets, all activities were greater at 24 and 48 h that at birth. In starved piglets, the increases were greater in all cases; the increase in cytosolic phosphoenolpyruvate carboxykinase was much more pronounced than for that for the particulate enzyme, with the former representing more than 50% of total at 48 h. The levels of gluconeogenic enzymes in the piglets in the early neonatal period would appear to be adequate for their needs and do not provide an explanation for their fasting hypoglycaemia. Hepatic levels of lactate, pyruvate, phosphoenolpyruvate, ketone bodies, and amino acids were determined in these piglets. No significant differences were observed in these metabolites between fasted and suckled animals except that glutamine was doubled in fed piglets, Evidence for the metabolic block in the livers of fasted animals was lacking and ketone bodies did not accumulate. These observations suggest that the limitations to gluconeogenesis result from unavailability of energy substrates and/or carbon precursors to the liver or the deficiency in their uptake.

Animals↗

The effects of dietary self-selection upon the overshoot phenomenon in starved-refed rats.

The food intake, liver composition and hepatic activity of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME) and acetyl CoA carboxylase (AcCoA Cx) were studied in starved-refed rats. When rats were refed a mixed diet for 3 days, food intake significantly increased (by 33%) from day 1 to 3 and the glycogen accumulation was maximal after 24 hours, but decreased significantly by day 3 (by 34%). In contrast, liver triglycerides sharply increased (10-fold) from day 1 to 3. Furthermore, during refeeding a large increase of G6P-DH, ME and AcCoA Cx was reached on day 3 when the average activity was 5.5- to 6.5-fold higher than before fasting. When rats were refed under conditions of self-selection (carbohydrates, lipids and proteins) total food intake was the same each day, but lipid and carbohydrate intakes varied reciprocally: lipid intake decreased whereas carbohydrate consumption increased during the 3 day refeeding period. Liver glycogen level was unchanged and both the triglyceride accumulation and the overshoot of lipogenic enzymes were highly attenuated: on day 3, they reached 50% of values observed in mixed diet refed rats. Administration of 8-azaguanine during refeeding under self-selecting conditions lowered food intake but had no effect on the pattern of food intake on the first day. In the following days, lipid intake fell dramatically. Azaguanine does not alter liver glycogenesis, but prevents both liver triglyceride accumulation and the overshoot of lipogenic enzymes.

Animals↗

Relationships between spontaneous food intake and metabolic activities in the dormouse (Glis glis L.).

1. The relationships between food intake self-selection and liver substrates (glycogen, fat) or activities of pyruvate kinase, glucose-6-phosphate dehydrogenase, malic enzyme, acetyl CoA carboxylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were determined during the spontaneous variations of body weight in the dormouse. 2. The results show that during the phase of increasing body weight, carbohydrate intake and enzyme activities involved in lipogenesis are on a high level. 3. On the last part of the body weight increasing phase, when lipid intake occurs, lipogenesis is depressed and a gluconeogenetic activity is set on, while total caloric intake is important and body weight is still increasing. 4. These metabolic changes are interpreted as a preparation to hibernating conditions in the dormouse.

Animals↗

Schedule of protein ingestion and circadian variations of glycogen phosphorylase, glycogen synthetase and phosphoenolpyruvate carboxykinase in rat liver.

The circadian rhythms of liver glycogen and hepatic activity of glycogen synthetase (GS), glycogen phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPCK) were studied in adult male rats. The rats either received a mixed diet ad libitum (10% protein) or a protein meal (1.85 g protein) given at 09:00 or 21:00 hours, with free access to a protein-free diet (separately-fed). When the protein meal was ingested at 09:00 hours it was followed by a drop in liver glycogen and a persistent daylight increase in GP and PEPCK activities, this phenomenon being attenuated when proteins were ingested during darkness (21:00 hours). Moreover in the latter case, the circadian rhythm of liver glycogen was modified (glycogen accumulation occurring later) and the protein meal ingestion was followed after a transient decrease by a high and sustained GS activity during a long period (12 hours). The drop in the hepatic glycogen level and the unusually long daylight period of sustained GP and PEPCK activities in separately-fed rats consuming the protein meal at 09:00 hours suggests that, in this case, part of the ingested nitrogen could have been catabolized and used for gluconeogenesis, thus explaining our previous observation of lower nitrogen retention observed in this group of rats.

Animals↗

Influence of diet, cortisol and insulin on the activity of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in the rat liver.

The influence of nutritional factors, such as fasting (24, 48 and 72 hours), protein free and high protein diets, and endocrine factors (cortisol and insulin) on the activity of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) in adult rats was studied. The circadian rhythm in the activity of these enzymes was studied at two protein levels: 15% and 50%. Under all conditions which favored gluconeogenesis the activity of PEPCK increased. Cortisol did not further increase the activity of PEPCK in rats fed a high protein diet. Regardless of the protein content of the diet, insulin did not reduce PEPCK activity. Dietary protein level had no influence on the usual rhythm of activity of PEPCK. On the other hand, the high protein diet increased it threefold. Under all experimental conditions we observed no changes in PC activity. This is probably due to the fact that PC is a constitutive enzyme and therefore is not adaptative.

Animals↗

Schedule of protein ingestion and circadian rhythm of certain hepatic enzyme activities involved in glucose metabolism in the rat.

The circadian rhythms of liver glycogen, plasma glucose, corticosterone and insulin, and hepatic activity of PK, G6PDH, ME, Ac, CoA carbox. PEP-CK and GPT were studied in adult rats. Animals either received a mixed diet ad libitum (8% protein) or a protein meal (1.1 g protein) given at 05:00 or 17:00 h, with free access to a protein-free diet (separately fed). When the protein meal was ingested during the lighted period (17:00) the 24-hour average level of liver PEP-CK was greater than in rats consuming protein during darkness (05:00). In the latter case, modification of the circadian rhythm of liver glycogen and of circadian rhythm of liver PK, G6PDH, ME and Ac.CoA carbox. activity (increase of 24 h average level, extension of period of high activity, sudden increase after ingestion of protein meal) were observed. Conversely, the circadian rhythm of plasma insulin and corticosterone and of liver PEP-CK and GPT activity were only slightly affected by the mode of feeding.

Acetyl-CoA Carboxylase↗