Christiane Larue-Achagiotis

The different effects of continuous night and day-time insulin infusion on the meal pattern of normal rats: Comparison with the meal pattern of hyperphagic hypothalamic rats

Abstract The different night and day-time effects of continuous intravenous infusion of various doses of insulin on the meal pattern have been investigated in normal rats. In the day-time a dose-response curve was apparent. An 86–220% increase in the 12 hr cumulative intake was due to an increase in the number of meals for the lowest dose and in both the size and number of meals for the highest doses. With the same doses given at night the average increase in 12 hr intake was limited to 27% and was not dose-dependent. The changes in the various features of the meal pattern, observed under the effects of continuous insulin infusion, resembled those observed after VMH lesions. The similarities between these effects can be considered to support the assumption of the role played by hyperinsulinism in hypothalamic hyperphagia.

Food deprivation induced parallel changes in blood glucose, plasma free fatty acids and feeding during two parts of the diurnal cycle in rats

The changes in plasma glucose and free fatty acid levels and in subsequent feeding induced by 4 to 10 hr of food deprivation were investigated in rats and compared for the two parts of the diurnal cycle. It was found that increasing fast duration at night induced a more rapid fall of plasma glucose and elevation of plasma free fatty acids than in the day. However, a similar increment of the first post fast meal was elicited by an identical decrement of blood glucose level for the two periods except after a 10 hr fast during the day. The acute effect of darkness and light per se being experimentally excluded, it was concluded that the size of the first meal following short term food deprivation was dependent throughout the diurnal cycle on the fast induced glucoprivic condition.

Dual effects of 2-deoxy-D-glucose on food intake in the rat: Inhibition at night and stimulation in the day-time

The effect of 2-deoxy-D-glucose on food intake in rats has been reexamined. The effects were compared following administration of 2-DG IP (250, 500, 750 mg/kg and saline) either at the beginning of a 12-hr dark or 12-hr light period. Ad lib food intake was recorded during the subsequent 24 hours. In the day-time 2-DG enhanced food intake. The increase was not dose-dependent. It was apparent only during the first four hours and was compensated during the following eight hours. At night, an inhibition in food intake was observed. This inhibition was mainly manifested during the first four hours and was not dose-dependent. However, a dose related compensation during the subsequent hours resulted in a dose-dependent inhibition of the nocturnal intake. A second expermient indicated that after an overnight fast 2-DG also inhibited the high food intake induced in the day-time. In a third experiment, insulin 10 IV SC combined to 2-DG was shown to further increase food intake in the day-time. At night the combined administration of insulin and 2-DG cancelled their respective opposite effects and no change of food consumption was observed. The results are interpreted in terms of the contrasted neuroendocrine and metabolic patterns prevailing in the two parts of the diurnal cycle.

Repeated short-fasting modifies the macronutrient self-selection pattern in rats

The daily caloric intake and circadian pattern of macronutrient self-selection were examined in rats subjected to 3 h of food and water deprivation at the beginning or at the end of darkness. When one sole 3-h period of deprivation was applied, rats showed a compensatory response characterized by an unscheduled diurnal and nocturnal increase in the intake of the three macronutrients. However, repeated short restrictions during 15 days promoted a scheduled time-dependent feeding response, characterized by an exclusive increase in carbohydrate and fat intake and a decrease in protein intake. Repeated deprivation at the onset of dark produced a feeding response confined to the dark phase, while late dark deprivation produced both a diurnal and nocturnal increase in feeding. After 15 days of repeated restriction, rats showed no body weight variations with respect to control rats fed ad libitum. These results show that short fasting elicits a time- and macronutrient-dependent feeding response in rats, which involves reorganization of the macronutrient self-selection pattern to promote a total daily caloric compensation. These results suggest that animals principally respond to the energy deficit produced by restriction.

Modifications in dietary self-selection specifically attributable to voluntary wheel running and exercise training in the rat

To explore the effects of physical exercise on total caloric intake, body weight gain, and dietary self-selection in rats, female rats of the Dark Agouti strain were placed on macronutrient self-selection. They had free access to running wheels during the whole experimental period. After 16 days of voluntary exercise only, they were trained on a motor-driven treadmill (16 m/min) at the beginning of the dark period. Runtime was progressively increased and reached 3 h per day (plateau). When trained, the rats decreased spontaneous wheel running. Voluntary wheel running did not modify body weight gain. However, it increased both carbohydrate and total caloric intakes. Exercise training reduced body weight gain, but did not further modify total caloric intake. Moreover it increased protein and reduced fat intakes. Most of the training-induced modifications were not side effects of fasting during exercise training.

Fast-induced changes in plasma glucose, insulin and free fatty acid concentration compared in rats during the night and day

Changes in PG, PI and PFFA were examined and compared in fed rats or after 0 to 12 hours of fasting, during the night or during the day. At night, a progressive decrease in PG and PI and an increase in PFFA were induced by 0 to 12 hours of food deprivation. During the light period a decrease in PG occurred only from the 6th hour of fasting. A slight, progressive increase in PFFA levels was induced from 0 to 12 hours of fasting, while no significant variation of PI levels was observed. The results are discussed in terms of relationships between blood glucose, PFFA levels, and food intake in control rats over the circadian cycle.

Exercise-training reduces BAT thermogenesis in rats

In the energy balance equation, physical activity represents one component of energy expenditure. From various studies it appears that exercise-training does not affect clearly thermogenesis which depends on brown adipose tissue (BAT) activity. In the present work we examine how exercise-training can influence food intake and body weight regulation in relation to BAT thermogenesis. The proton conductance of the uncoupling protein of BAT was examined in male adult Wistar trained 2 h/day for 20 days and compared to that of sedentary (2 h of fasting instead of exercise) or control animals. All animals were provided with separate sources of the 3 macronutrients (protein, fat and carbohydrate) containing an identical percentage of vitamins, salt mixture and cellulose powder. At the end of training, rats were placed at 5 degrees C during 10 days, then during 4 days at 28 degrees C. This condition has been demonstrated to favour and amplify BAT responsiveness to moderate modifications of stimulation. The body weight of trained rats became significantly lower than that of the control and sedentary rats and this difference persisted all throughout the experiment. When placed at 5 degrees C, all rats increased their total ingestion: control rats enhanced fat intake, while sedentary and trained rats enhanced carbohydrate ingestion. When placed at 28 degrees C, all rats had identical total energy and that of the 3 items intakes. BAT proton conductance was about 40% lower in the trained compared with the sedentary plus the control rats. This indicated a lower BAT thermogenic activity in the trained animals. It could be concluded that exercise-training in rats induces negative energy balance; the reduced BAT activity could restrain weight loss and overeating.

Energy balance in an inbred strain of rats: comparison with the Wistar strain.

Food intake and body weight gain were examined in two groups of male rats (7 weeks): an inbred strain, Dark Agouti (DA, n = 12) and a noninbred strain, Wistar (n = 13). The animals were allowed to select their diet from separate sources of the three macronutrients protein, fat, and carbohydrate. After 10 days of adaptation to the diets, body weights and food intakes were measured for 3 weeks. During this period, meal patterns were recorded for at least 5 days in each rat. Then, rats were switched to a chow diet (UAR, A.O4) for 10 days. The total caloric intake of DA rats was 60% that of Wistar rats, while their body weight gain was 25% that of Wistar rats (1.3 g/day in DA vs. 5.3 g in Wistar). However, when energy intake was related to total body weight, there was no difference in energy ingestion. It was observed that DA rats ingested mainly proteins (45%) and fats (41%), while Wistar rats ingested an identical proportion of proteins and carbohydrates (40%). The percent of total white adipose tissue to total body weight was identical in both strains (6% on average). Brown adipose tissue thermogenic activity of DA rats was threefold higher than in Wistar rats. This could be one of the elements responsible for the lower body weight gain of this group of rats. Self-selected food intake of the inbred DA strain of rats, in contrast to what was expected, was greatly variable.

Exercise training decreases body fat more in self-selecting than in chow-fed rats

This study was designed to examine the influence of exercise training on body weight gain and feeding pattern in rats placed on a self-selection or a chow diet regimen. Adult, male, Wistar rats were submitted to daily 2-h treadmill exercise for 28 days (about 50% of VO2 max) at the beginning of the nocturnal period. Two other groups of rats were examined during the same time: a sedentary group that was deprived of food and water during the training session and a control group without any treatment. Food intakes were continuously recorded. For both feeding regimens, trained rats, relative to their respective controls, showed at the end of the experiment a reduction in body weight gain due to a reduced body fat deposit. Moreover, white adipose tissue (WAT) mass of self-selecting rats was smaller than in chow-fed rats. Exercise training decreased plasma glucose level in chow-fed rats and plasma insulin level in self-selecting rats. In self-selecting rats, food intake was slightly increased due to enhanced protein intake during the nocturnal period and fat intake increased both during the nighttime and daytime periods, whereas in chow-fed rats, food intake was decreased during the daytime period. These results show that, in rats placed on a self-selection regimen, exercise training increased fat consumption but reduced WAT. This could be a consequence of an increased lipolytic capacity of adipocytes in self-selecting trained rats. Thus, it appears from these results that the diets carbohydrate-to-fat ratio can be an important parameter in shaping the interaction between exercise and body weight.

Feeding rate and responses to food deprivation as a function of fasting-induced hypoglycemia

The relation between hypoglycemia induced by 3 hr of food removal at various times throughout the day and the amount eaten during the corresponding ad-lib periods was examined in rats. It was found that the 3-hr-deprivation fall in blood glucose was different between the night and the daytime and also between the beginning and the end of the daytime. A highly significant correlation existed between the 3-hr ad-lib intake and this time-dependent fall in blood glucose. Moreover, the correlation between the same fall in blood glucose and increases in subsequent intakes after 3-hr deprivation was also significant. The conclusion is drawn that rats eat at a rate just required to prevent hypoglycemia under ad-lib conditions and that after food deprivation they transiently increase this rate to correct the fall in blood glucose and to reestablish the required supply of glucose to tissues.