Bela Szepesi

Long-Term Effects of Starvation-Refeeding in the Rat

The effects of one vs. two episodes of starvation-refeeding were studied in young male rats as a function of elapsed time between the two episodes of starvation-refeeding. Starved-refed rats ate more and gained weight faster than ad libitum-fed rats. The difference in weight gains could be attributed to the greater amount of body fat in the starved-refed rats. The responses of four NADP-linked liver dehydrogenases:isocitrate dehydrogenase (ICD)/LS-isocitrate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.42), glucose-6-phosphate dehydrogenase (G6PD)/D-glucose-6-phosphate:NADP oxidoreductase (EC 1.1.1.49); 6-phosphogluconate dehydrogenase (6PGD/6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.44); and malic enzyme (ME)/L-malate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.40) were studied. Starvation-refeeding caused an overshoot of G6PD, 6PGD, and ME, but not of ICD. A second episode of starvation caused an even greater enzyme overshoot; this difference persisted for 3 weeks with G6PD and for 2 weeks with 6PGD and ME. No significant differences in blood cholesterol were detected.

Specificity of the disaccharide effect in the rat.

Male rats were starved and refed diets containing 40% disaccharides (maltose, trehalose, sucrose, turanose), trisaccharide (melezitose), starch, or the monosaccharide equivalents. Responses of hepatic glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), fatty acid synthetase (FAS), and total liver lipid (TLL) or changes in concentration of portal blood total carbohydrate and fructose were determined following refeeding of the different carbohydrate diets. Maltose, trehalose, sucrose, and turanose refeeding resulted in G6PD and ME responses which were higher than the responses to their component monosaccharides (disaccharide effect). Starch refeeding decreased the responses of G6PD, ME, and FAS when compared to refeeding of glucose. Refeeding diets containing fructose (sucrose, turanose, melezitose, and monosaccharide equivalents containing fructose) increased the responses of G6PD, ME, FAS, and TLL. No correlation between portal blood carbohydrate concentration and hepatic enzyme levels could be demonstrated. It is concluded that readily digestible disaccharides produce an effect which is greater than the effect produced by their monosaccharide equivalents. If these disaccharide configurations are fed as part of a trisaccharide or polysaccharide, the disaccharide effect is no longer discernible.

Comparison of the fructose effect and the starve-refeed response of rat liver enzymes

Abstract The magnitude of the starve-refeed response and the effect of dietary fructose on the activities of hepatic glucose 6-phosphates dehydrogenase (G6PD) and malic enzyme (ME) were studied. The magnitude of increase in enzyme activity was similar in rats starved and refed the glucose diet or fed the fructose diet ad libitum when compared to rats fed the glucose diet ad libitum . In rats starved and refed the fructose diet, the starve-refeed response and the fructose effect were additive, suggesting that the two responses have different mechanisms. When the enzyme response to a subsequent starve-refeed episode was studied it was found that a previous starve-refeed episode increased the subsequent response to starvation-refeeding, whereas prefeeding the fructose diet ad libitum did not. Both the starve-refeed response and the fructose effect were inhibited by 8-azaguanine, suggesting a requirement for de novo RNA synthesis. The data suggest that the nature of requirement for de novo RNA synthesis is different in the starve-refeed response from the requirement for de novo RNA synthesis for the fructose effect.

Effect of dietary carbohydrates on food efficiency and body composition in adult male rats during normal growth and during recovery from food restriction

Abstract Male Wistar rats about 8 to 9 weeks of age were fed diets which contained 43% of the calories as glucose, maltose, uncooked cornstarch, sucrose, or invert sugar. Half the animals in each dietary group were made to lose 37% of their initial body weights by food restriction and then allowed to eat their food ad libitum for 31 days (restricted-refed groups). The rest of the animals were fed ad libitum for 71 days (unrestricted groups). There were no dietary effects on food efficiency during recovery or in the percent body fat after recovery in the restricted-refed animals (ANOVA). However, the disaccharides produced a greater weight of body fat than starch or monosaccharides. In unrestricted animals, invert sugar, sucrose, and maltose were used with higher efficiency than starch or glucose. Rats fed the maltose diet ate 12% more food than did the animals fed glucose and had food energy efficiency and body fat percentages 62% greater than those eating the glucose diet. Maltose also produced similar differences compared to cornstarch. Although mean body fat percentages produced by sucrose or invert sugar feeding were greater than those caused by glucose and starch, the differences were not significant. Thus a fructose effect on body fat was not shown statistically.

Effect of refeeding raw and cooked starches on hepatic enzyme activities of rats.

I. Responses of hepatic glucose-6-phosphate dehydrogenase (EC I . I . I .49; G6PD), malic enzyme (EC I . I . I .40; ME), acetyl-CoA carboxylase (EC 6.4. I . 2; ACAC), and fatty acid synthetase (FAS) were studied in male Wistar rats after a period of starvation and refeeding of diets containing 400 g glucose, or raw or cooked starches as the source of carbohydrate/kg. Starches fed included maize, potato, wheat, rice, and tapioca. 2. When compared to the responses of rats given the glucose-containing diet, rats given raw maizeor rice-starch-containing diets had a significantly lower ME response, and rats given raw potato starch had significantly lower responses of G6PD, ME, ACAC, and FAS. The enzyme responses of rats given cooked starches were similar to those of glucose-fed rats, except that rats given cooked wheat starch had significantly lower G6PD and ME responses than did glucose-fed rats. 3. When the enzyme responses to refeeding of the same starch source in either raw or cooked form were compared, it was found that (a) the FAS response was significantly higher to cooked than to raw maize starch, (b) the G6PD and ACAC responses were significantly higher to cooked than to raw tapioca starch, (c) the G6PD, ME, ACAC, and FAS responses were significantly higher to cooked than to raw potato starch. 4. The results suggest that reported differences in the lipogenic enzyme responses between simple sugars and starch may in some instances be magnified because of the use of uncooked starches in experimental diets.

Preliminary crystallographic study of glucose-6-phosphate dehydrogenase from rat liver

Crystals of D-glucose-6-phosphate: NADP+ oxidoreductase were obtained with the hanging drop, vapor diffusion and batch methods from ammonium sulfate-containing solutions. X-ray diffraction photographs indicate that the crystals belong to the orthorhombic space groups I222 or I2(1)2(1)2(1) with unit cell dimensions of a = 66.0 A, b = 140.8 A and c = 177.8 A. These data, together with results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and crystal density experiments, indicate that there is one 116,000 Mr dimer per asymmetric unit. The crystals diffract to at least 2.2 A and are suitable for X-ray crystallographic structure determination.

Insulin and Enzyme Responses in Three Strains of Rats

Summary Three groups of male weanling rats of the BHE, Wistar, and inbred BHE strains were fed a 6% corn oil, 40% protein, 45% carbohydrate diet until they were 100 days old. Half of the animals were killed after a 24-hr fast while the remaining animals were killed without prior fasting. Animals of the BHE and IN-BHE strains had lower levels of IRI and higher blood glucose levels than animals of the Wistar strain. Strain differences in the fasting and nonfasting activities of the hepatic enzymes and in the lipid levels of the blood and liver appeared to be related in part to the insulin status of these animals. However, the data also suggested that different mechanisms of internal control of intermediary metabolism exist for each of these strains.

Persistence of Increased Inducibility of NADP-linked Dehydrogenases in Rat Liver

Summary Liver cells of rats starved and then refed a high-protein diet retain the cellular memory of starvation and respond to a high-carbohydrate diet by developing the enzyme overshoot. A second cycle of starvation causes an even greater overshoot and the increased capability after one starve-refeed cycle is retained during and after a second cycle. The best explanation of the data is that during refeeding the high-carbohydrate diet after starvation new RNA is formed which persists during subsequent dietary manipulations.

The effects of low-dose Bay-m-1099 (Miglitol) on serum lipids and liver enzyme activity of obese and obese-diabetic corpulent rats.

1. Groups of lean, obese, and obese-non-insulin-dependent diabetic LA/N-cp and SHR/N-cp rats were administered the a-glucosidase inhibitor Miglitol (150 mg/kg diet, ad libitum) from 8 until 15 weeks of age. 2. Phenotype effects (obese greater than lean) were present for weight gain, adiposity, serum glycemic and lipid parameters, and for liver glucokinase, glucose-6-phosphate dehydrogenase, and malic enzyme activity. Miglitol treatment was associated with improvements in glucokinase and malic enzyme in both strains, and in improvements in glycemic parameters in obese rats. 3. These results are consistent with variable improvements in glycemic control and insulin action following low dose Miglitol treatment, and indicate that indirect effects of the drug on insulin sensitivity in peripheral tissues and on glucoregulatory enzymes may contribute to the glycemic improvements observed with this drug, while greater dosages or longer treatment may be required to observe comparable improvements in adiposity or plasma lipid profiles.

Effect of tolbutamide and exogenous insulin on the metabolic responses of rats.

Summary The effect of tolbutamide or exogenous insulin on the levels of certain enzymes, blood glucose, serum IRI, and lipids in the blood, liver, and carcass of Wistar rats was studied. The drugs, administered from weaning to 100 days of age, appeared to increase the activity of G6PD, ME, ICD, CE, and the level of liver cholesterol. Blood glucose, IRI, and the level of lipid in the liver and carcass were unaffected by the treatments. These findings show that slight changes in insulin status early in life may result in markedly different metabolic patterns at maturity.