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M Lavau

Publications and source records attributed to M Lavau.

At least 73 records · Page 4Linked to original sources
PubMed1982

Evidence for a high fatty acid synthesis activity in interscapular brown adipose tissue of genetically obese Zucker rats.

Obese (fa/fa) rats (30 days old) exhibited a 50% increase in the weight of interscapular brown adipose tissue compared with their lean (Fa/fa) littermates. The tissue weight increase was accounted for by an increased fat content. Lipogenesis in vivo, as assessed by the incorporation of 3H from 3H2O into lipid, was increased 5-fold in brown adipose tissue of obese as compared with lean rats. Accordingly, acetyl-CoA carboxylase, fatty acid synthetase, citrate-cleavage enzyme and malic enzyme in this tissue were 4-8 times more active in obese than in lean rats.

Adipose Tissue, Brown↗
PubMed1982

Variations of glucose metabolism by fat cells from three adipose depots of the rat.

Fat cells isolated from the epididymal (E) and dorsal subcutaneous (S) depots from 150g male Wistar rats were similar in size, but differed markedly in glucose metabolism. Retroperitoneal (RP) fat cells were slightly larger but were metabolically similar to epididymal fat cells. Basal incorporation of [1-14C] glucose into fatty acids was lower in S than E and RP, CO2 production and glyceride-glycerol synthesis were similar in all three; and lactate production was increased in RP and S compared to E. S adipocytes exhibited a blunted respond to both submaximally and maximally-stimulating concentrations of insulin compared to RP and E adipocytes in glucose incorporation into fatty acids, CO2 and lactate production, but not glyceride-glycerol. Maximally insulin-stimulated fatty acid synthesis by S fat cells was 19% and 29% of the values in E and RP fat cells respectively. Basal and maximally insulin-stimulated glucose transport (2-deoxy [14C] glucose uptake) was depressed by 30%-40% in S cells compared to E and RP. Thus, the decreased basal glucose utilization of S could be attributed primarily to a decreased glucose transport capacity. The markedly lower insulin-stimulated glucose metabolism in S fat cells, however, may be explained by alterations of the capacities for both transport and intracellular metabolism. Subcutaneous fat cells were also somewhat less sensitive to submaximal doses of insulin and this was reflected in rightward shift in the dose-response curves for 2-deoxyglucose uptake and fatty acid synthesis. The decreases in insulin stimulated glucose oxidation and fatty acid synthesis were paralleled by decreases in the major lipogenic enzymes. Although the reason for these variations in the capacity for glucose metabolism among depots is unknown, they are important in assessing the metabolic function of the whole adipose organ.

Adipose Tissue↗
PubMed1982

Effects of high-fat diet on glucose metabolism in isolated pancreatic acini of rats.

The purpose of the present study was to document the metabolism of glucose and its responsiveness to insulin in isolated pancreatic acini from rats fed either a low- or high-fat diet. The different steps investigated were labeled glucose oxidation, lactate production, hexokinase activity, and glucose transport, which was assessed by using both 3-O-methylglucose and 2-deoxyglucose. The acinar capacity to metabolize glucose (sum of CO2 plus lactate) was decreased by 50% by feeding the rats a high-fat diet. The impairment of glucose metabolism could not be explained by a defect in the glucose phosphorylation step because hexokinase activity was not changed in isolated acini from rats fed a high-fat diet. The effect of a high-fat diet was entirely accounted for by a reduction in the glucose transport rate that was achieved through a decrease in glucose transport Vmax with no change in Km. We could not detect any effect of insulin on glucose metabolism or 2-deoxyglucose uptake, whatever the diet composition. This work establishes that a high-fat diet, known to markedly alter pancreatic exocrine enzymes, also induces a large decrease in acinar glycolytic flux, raising the question of the relation between these two sets of adaptive changes.

3-O-Methylglucose↗
PubMed1982

Development of hepatic and adipose tissue lipogenic enzymes and insulinemia during suckling and weaning on to a high-fat diet in Zucker rats.

This study was designed to monitor the developmental changes in insulinemia and lipogenic enzyme activities in both inguinal adipose tissue and liver during suckling (7, 9, 14, and 17 days of age) and weaning (22 and 30 days of age) on to either a low-fat or a high-fat diet in lean (Fa/fa) and obese (fa/fa) rats. Tissues were removed through surgery and genotypes were retrospectively determined. During suckling, there was no difference in liver enzyme activities between the two groups. In contrast, adipose tissue fatty acid synthetase was increased by 50% and citrate cleavage enzyme and malic enzyme by 30% by 9 days of age. By 17 days of age, there was a threefold elevation in these enzyme activities and 6-phosphogluconic dehydrogenase and a twofold increase in glucose-6-phosphate dehydrogenase per inguinal fat pad in fa/fa versus Fa/fa. Consistent with these results, fat pad weight was increased by 20%, 50%, and 100% at 9, 14, and 17 days of age, respectively, in obese as compared to lean pups. However only by 17 days of age could a slight but significant increase in insulin level be detected in obese pups. Enlargement of inguinal fat pad accelerated after weaning on to a low-fat diet and still more after weaning on to a high-fat diet. Weaning on to a low-fat diet elicited an induction of hepatic lipogenic enzymes two or three times greater in fa/fa than in lean pups, while weaning on to a high-fat diet blunted the differences between genotypes. The lipogenic enzyme activities displayed per total inguinal fat were three to ten times greater in obese than in lean pups, regardless of the diet. However, adipose tissue lipogenic enzyme activities were much lower after weaning on to a high-fat than on to a low-fat diet in obese pups. The high-fat diet was as effective as the low-fat diet in triggering hyperinsulinemia in obese pups. The increased adipose tissue capacity for lipogenesis, starting during the suckling period, could play an important etiologic role in the development and maintenance of obesity in the Zucker rat.-Bazin, R., and M. Lavau. Development of hepatic and adipose tissue lipogenic enzymes and insulinemia during suckling and weaning on to a high-fat diet in Zucker rats.

Adipose Tissue↗
PubMed1982

Inguinal fat pad weight plotted versus body weight as a method of genotype identification in 16-day-old Zucker rats.

By plotting the weights of inguinal fat pad versus body weights in littermates from fa/fa X Fa/fa crosses, we observed that the data distributed along two widely separated regression lines as of 16 days of age. This procedure enabled us to determine unequivocally the genotype of every pup in seven litters. By its rapidity, its simplicity, and reliability, this method of genotype identification may be useful to many investigators.

Adipose Tissue↗
PubMed1981

Role of fatty acid synthesis in the control of insulin-stimulated glucose utilization by rat adipocytes.

A decreased capacity for fatty acid synthesis is associated with a decreased insulin effect on glucose metabolism in large fat cells and fat cells from rats fed a high-fat diet. We have investigated the relationship between these processes by specifically inhibiting fatty acid synthesis with (-)-hydroxycitrate (2.5 mM), an inhibitor of citrate cleavage enzyme, and cerulenin (0.05 mM), an inhibitor of fatty acid synthetase. (-)-Hydroxycitrate and cerulenin decreased maximally insulin-stimulated fatty acid synthesis from [6-(14)C]glucose to 10% and 25% of controls, respectively, while only (-)-hydroxycitrate decreased basal values. Oxidation of [1-(14)C]glucose in the presence of insulin was markedly depressed by each inhibitor. Thus, the percent increase over basal value was decreased from 540% in controls to 151% and 154% by (-)-hydroxycitrate and cerulenin, respectively. In contrast, oxidation of [6-(14)C]glucose was slightly enhanced by both inhibitors. Thus, oxidation of glucose via the pentose shunt was reduced, while Krebs cycle oxidation was unaffected. Basal and insulin-stimulated incorporation of [1-(14)C]glucose and [6-(14)C]glucose into glyceride-glycerol and basal lactate production was unchanged by the inhibition of fatty acid synthesis. Insulin-stimulated lactate production was halved by the inhibition of fatty acid synthesis. Total glucose utilization, as assessed by measuring the disappearance of glucose from the medium, was not detectably changed by inhibiting fatty acid synthesis under basal conditions, but insulin-stimulated values were decreased to 52% and 64% of control by (-)-hydroxycitrate and cerulenin, respectively. This occurred despite the fact that neither agent affected the initial rate of 2-deoxyglucose uptake, or glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase activities. These data therefore provide direct evidence that a limitation of the fatty acid synthetic pathway decreases the ability of insulin to stimulate both pentose shunt glucose oxidation and overall glucose utilization, but not Krebs cycle oxidation or glyceride-glycerol synthesis. The enzymatic capacity of the fat cell for fatty acid synthesis is therefore an important determinant of insulin-stimulated glucose utilization.-Fried, S. K., M. Lavau, and F. X. Pi-Sunyer. Role of fatty acid synthesis in the control of insulin-stimulated glucose utilization by rat adipocytes.

Adipose Tissue↗
PubMed1979

Adrenaline responsiveness of glucose metabolism in insulin-resistant adipose tissue of rats fed a high-fat diet.

The effects of adrenaline (0.5 microM) and the combination of adrenaline and insulin (1.7nM) on [6-14C]glucose metabolism were assessed in epididymal fat-pads from rats fed either a low- or high-fat diet. The response of lipolysis to adrenaline was clearly diminished in fat-fed rats. Insulin added to adrenaline inhibited the lipolysis by 50% regardless of the diet. Glucose utilization in adipose tissue of fat-fed rats was markedly stimulated by adrenaline (glucose uptake was increased 3-fold and the production of CO2 and the glycerol moiety of acylglycerol was increased 4-fold). However, adipose tissue from fat-fed rats was resistant to the effect of insulin to produce a further increase in adrenaline-stimulated glucose uptake. The intracellular capacity of lipogenesis on the one hand, and the production of CO2 and the glycerol moiety of acylglycerol on the other, are of prime importance in the action of insulin and adrenaline on glucose utilization in this model.

Adipose Tissue↗
PubMed1979

Diet composition and insulin effect on amylase to lipase ratio in pancreas of diabetic rats.

In man and in rat, the diabetic state is associated with diseases of exocrine pancreatic function. In this work, streptozotocin diabetes was shown to lead to a 95% decrease in the amylase to lipase ratio in rats. Diabetes was reversed by either pancreas transplantation or insulin treatment. Transplantation of neonatal pancreases was successful in reversing the diabetic-induced alterations of exocrine pancreatic function. To assess whether insulin acts directly on the exocrine pancreas, or through the enhancement of glucose utilization, animals were fed either a low-fat diet or a high-fat diet during insulin treatment; this latter diet is well known to impair insulin's effect on glucose metabolism. When diabetic rats were fed a low-fat diet, insulin treatment was able to correct the hyperketonemia and to reverse the amylase to lipase ratio to the prediabetes level. In contrast, the insulin treatment failed to restore the amylase to lipase ratio when the diabetic rats were fed the high-fat diet. Despite insulin treatment, the hyperketonemia worsened implying that glucose utilization remained low as would be expected on high-fat diet. The dependence of the insulin effect upon diet composition demonstrates that the rate of glucose metabolism is the primary factor in the regulation of amylase to lipase ratio.

Amylases↗
PubMed1979

Mechanism of insulin resistance in adipocytes of rats fed a high-fat diet.

Insulin's ability to stimulate glucose metabolism is severely diminished in the adipose tissue of rats fed a high-fat diet as compared to that of rats fed a low-fat diet. To elucidate the mechanism for this effect we have measured the binding of insulin, the hormone effect on 2-deoxyglucose uptake and the major pathways of [1-(14)C]glucose metabolism, and the activity of lipogenesis-related enzymes in adipocytes of rats fed a low- or high-fat diet for 7 days. Rats fed high- or low-fat diets bound equal amounts of insulin per adipocyte at all insulin concentrations tested. Basal and maximally insulin-stimulated 2-deoxyglucose uptake per fat cell were reduced in high-fat-fed rats. However, the insulin stimulation over basal was the same in both groups (230%). Submaximal doses of insulin produced equivalent increments of 2-deoxyglucose uptake in both groups, as would be predicted by the binding studies. The effect of both submaximal and maximal insulin concentration on the labeling of CO(2) and fatty acids was markedly decreased by high-fat feeding. The insulin response of the glyceride-glycerol pathway was less severely, though significantly, reduced. Acetyl CoA carboxylase and malic enzyme in adipocytes of high-fat-fed rats were reduced to 13% of the activity in the low-fat-fed rats. Glucose-6-phosphate and 6-phosphogluconate dehydrogenases were decreased to 20% and 34% of their activities in low-fat-fed rats, respectively. These reductions paralleled the changes in insulin-stimulated glucose oxidation and fatty acid synthesis. The data therefore strongly suggest that the blunted response of glucose metabolism to insulin in adipocytes of high-fat-fed rats is a result of a decreased intracellular capacity to utilize glucose for lipogenesis.

Adipose Tissue↗
PubMed1976

Glucagon, insulin, and gluconeogenesis in fasted odd carbon fatty acid-enriched rats.

Forty-eight male rats were fed a nutritionally complete diet containing 30% of dietary energy as fat. For 24 animals (control) the fat source was corn oil, for the remaining 24 rats (experimental) the fat source was a triundecanoin-corn oil mixture (7:3, wt/wt). After 6 wk, groups of control and experimental rats were killed after 0, 24, and 48 h of fasting. In the experimental group, adipose tissue fatty acids contained, on average, 280 mmol undecanoate/mol fatty acid. In the control group, no odd-numbered fatty acids were present. During fasting, the experimental groups had higher plasma glucose and alanine levels, higher plasma insulin-to-glucagon ration, and lower liver phosphenol pyruvate caboxykinase. The results suggest that the terminal propionate residues generated when odd carbon fatty acids are oxidized become gluconeogenic precursors and cause a reduced need for gluconeogenesis from protein.

Adipose Tissue↗
PubMed1975

[U-14C]glucose metabolism in vivo in rats rendered obese by a high fat diet.

Estimates of the glucose pool, the glucose space, the turnover rate, and the recycling of glucose were made after the injection of [U-14C]glucose into (a) obese rats fed a high fat diet and (b) rats fed a carbohydrate diet. The specific activity--time curve consisted of two components. Physiological parameters were calculated by using a two-compartment model. The glucose pool and glucose space were the same in both groups of rats. The turnover rate was 1.96 mg. min-1 for the carbohydrate-fed rats and 1.55 mg. min-1 for the fat-fed rats. There was about 12 percent recycling in both groups. In the carbohydrate-fed group, another approach based on simultaneous use of [6-14C]glucose and [6-3H]glucose yielded nearly the same values for these parameters. Respiratory excretion of CO2 and the incorporation of labeled glucose into lipids of some tissues were also measured. The rate of excretion of labeled CO2 and the conversion of labeled glucose into fatty acids in fat-fed rats were lower than in the carbohydrate-fed rats by 50 percent and 80 percent, respectively. More glucose was diverted into glyceride glycerol in the fat-fed group. It is suggested on the basis of the results that glyceride glycerol can serve as a gluconeogenic substrate in these rats where the turnover rate of glucose is much higher than the daily intake of carbohydrates.

Adipose Tissue↗