Jean Peret

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)

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.

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.

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.

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.

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

SummaryThe 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.

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

SummaryThis 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 1ml 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.