Biomedical subjects
J Le Magnen
Publications and source records attributed to J Le Magnen.
[Lipogenesis, lipolysis and feeding rhythms].
Recordings of rat's diurnal ad libitum feeding patterns and responses to short term food deprivation suggested that analysis of diurnal feeding rhythms could provide a clue for understanding mechanisms involved in control and regulation of food intake. A simultaneous recording of free feeding patterns and of respiratory exchanges showed that a nocturnal positive energy balance and hyperphagia were mainly due to a diversion of ingested nutrients to fat deposition while negative energy balance and hypophagia during daytime were an effect of fat mobilization and oxidation. Further it was demonstrated that a neuroendocrine diurnal cycle underlined the lipogenesis-lipolysis cycle with hyper-insulinism and glucose tolerance at night, hypoinsulinism and glucose intolerance during the day. Similar phenomena were found along with the human scheduled feeding. Negative correlations between nocturnal lipogenesis and subsequent daytime lipolysis and the diurnal cycle of free fed rats compared to experimentally induced and reversible obesity and to seasonal cycles of hibernators give evidence on the nature of the lipostatic mechanism and its monitoring by hypothalamic ventromedial nuclei.
[Historical development of the concepts of hunger, satiety and appetite].
Explore the source record for details and available documents.
Effects of 2-deoxy-D-glucose on food and water intake and body temperature in rats.
Comparisons between early daytime and early nighttime effects of 2-deoxy-D-glucose (2DG) injections on food and water intake and rectal temperature were made. Food intake was significantly enhanced by 2DG injections regardless of the phase of the light cycle. In the daytime, water intake was increased by a lower dose of 2DG (200 mg/kg, IP) but there was no further increase at a higher dose (400 mg/kg). At night, the lower dose of 2DG had no effect on water intake but the higher dose suppressed the water intake normally associated with feeding. Administration of 2DG reduced preprandial rectal temperature in a dose dependent fashion in both phases of the light cycle. However, preprandial rectal temperatures were decreased more at night than during the daytime after injection of the higher dose of 2DG. Therefore, 2DG-induced hypothermia is dependent on both the dose of 2DG injected and the phase of the light cycle in which glucoprivation is produced. Furthermore, below a certain level of body temperature, rats markedly reduced drinking behavior while maintaining but not increasing their feeding response to 2DG-induced glucoprivation. These results suggest that behaviors may be directed toward preservations of body temperature in preference to relief of hunger by eating and of thirst by drinking.
Hypothalamic modulation of energy expenditure.
The acute effects of electrical stimulation of the hypothalamus on energy expenditure as measured by indirect calorimetry were investigated in 20 unanaesthetized rats. Thirty sec of stimulation increased both O2 consumption and respiratory quotient (R.Q.). The largest magnitude hypermetabolic response (39% mean peak increase in O2 consumption) was produced by stimulation of the ventromedial hypothalamic nucleus. Stimulation of the lateral hypothalamus produced hypermetabolic effects similar to but smaller than those produced by medial stimulation. A number of considerations suggest that the hypermetabolism is not secondary to changes in motor activity, carbohydrate utilization or blood glucose levels. Consequently, these data suggest that the hypothalamus modulates energy expenditure through changes in non-shivering thermogenesis. These metabolic changes may modulate the effects of various hypothalamic manipulations on body weight.
Effect of amygdaloid lesions on ethanol intake in rats.
The effect of electrolytic lesions of the amygdala on ethanol intake in ethanol naïve rats has been studied. Rats with basolateral nuclei and lateral nuclei lesions showed a reduced neophobic response to an ethanol solution. However, the ethanol intake was too small in normal and lesioned rats to augment aversion through conditioning. Oral intake of ethanol supplemented by intraperitoneal ethanol injection to reach 2 g/kg indeed enhanced the initial sensory aversion to ethanol. This induced aversion was attenuated after basolateral lesions. An initial aversion to a mixed ethanol-sucrose solution was abolished after basolateral lesions, while the lateral lesions induced an initial preference for this solution. The initial oral intake of ethanol-sucrose in normal rats was again too small to induce the conditioned taste aversion (C.T.A.). Despite the high oral intake of this solution, rats with basolateral lesions did not show a conditioned aversion while laterally lesioned rats exhibited a strong conditioned aversion to the ethanol-sucrose mixture. The results which confirm the suppression of the C.T.A. by basolateral amygdala lesions are discussed in relation to the role of toxicophobia in ethanol intake by rats.
Relationship between initial sensitivity to ethanol and the high alcohol intake in dependent rats.
The high spontaneous intake of ethanol, which can be induced in rats after a period of forced administration, may be used to study the altered state created in the C.N.S. by the chronic exposure to ethanol. The relationship between the initial acute sensitivity to ethanol and this induced high oral intake has been examined in rats. Initial sensitivity was determined in two groups of rats either by a test of motor impairment or by alcohol induced hypothermia. After 15 days of daily IG administration of 10 g/kg, rats were submitted to the ethanol presentations which display the high voluntary intake. Two groups of controls were initially tested for their motor impairment or hypothermia respectively under ethanol and then treated for 15 days with saline injections. The results indicate a highly significant negative correlation between initial sensitivity and the level of dependence induced by a chronic treatment and manifested by a voluntary high intake. In control groups, the low intake of ethanol observed in the final test was not correlated to the initial sensitivity to ethanol as tested by hypothermia but weakly correlated to sensitivity measured by motor impairment. The results are discussed in terms of mechanisms which determine the voluntary intake of ethanol in ethanol naive and dependent rats.
Effect of long-term insulin on body weight and food intake: intravenous versus intraperitoneal routes.
The effects of continuous intravenous (i.v.) or intraperitoneal (i.p.) infusion of regular insulin on food intake (FI) and body weight (BW) were examined. When rats were infused i.v. with insulin at 0.2 IU/h for 14 days, BW increased until the 10th day and then plateaued, whereas FI was augmented until the end of treatment. The 24-h hyperphagia was mainly due to a diurnal increase in FI--resulting mainly from a large augmentation in meal number, with unchanged meal size. Nocturnal meal number increased and meal size decreased so that nocturnal FI was not affected. At the cessation of infusion, rats became hypophagic and lost weight. Another group of animals, infused with a lower dose (0.1 IU/h), showed that the increases in BW and FI were dose-dependent. Insulin infused (0.2 IU/h) for 14 days via an i.p. catheter increased FI and BW. The 24-h increase in FI was again mainly due to an enhanced diurnal intake, but at the cessation of insulin infusion rats did not lose BW. In rats infused with insulin at 0.1 IU/h for 14 days, BW and FI did not increase. In rats infused via an implanted minipump with insulin at 0.1 IU/h for 7 days, however, BW increased significantly over controls for the first 3 days, without any significant change in FI, the discrepancy between results observed here and other results is discussed, these effects suggest a relative ineffectiveness of the i.p. route compared to i.v.
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.
Insulin action during fasting and refeeding in rat determined by euglycemic clamp.
To further characterize the role of insulin in glucose metabolism during fasting and refeeding, euglycemic-hyperinsulinemic clamps were performed in control, 3 day-fasted, and 3 day-fasted then 3 day-refed rats. Glucose production and utilization were measured by using [3-3H]glucose. In control and refed rats, hepatic glucose production was totally suppressed at insulin concentration higher than 500 microU/ml; by contrast, during fasting, hepatic glucose production was not suppressed even at insulin concentration tenfold higher. Maximal increment of glucose utilization was lower in fasted than in control rats. Three days of refeeding restored almost entirely normal responses to insulin for glucose utilization. Blood glucose concentration was clamped at a different level in fasted and in control and refed rats; however, increment in glucose clearance in response to insulin was lower in fasted rats than in the two other groups. Thus fasting produces a state of insulin unresponsiveness both at the hepatic and peripheral levels, normal responsiveness being restored after 3 days of refeeding.
Cephalic phase of insulin secretion and food stimulation in humans: a new perspective.
Insulinemia and glycemia were measured at a 1-min interval at the hour of a lunch meal in human subjects. When no food was presented to naive subjects (n = 4), cyclic oscillations of insulinemia were found (period, 12-20 min; amplitude, 2.8-10.3 microU/ml). It is proposed that these spontaneous oscillations must be taken into consideration when evaluating the insulin response on cephalic contact with food stimuli; they might otherwise constitute a source of artifacts. Four subjects were then submitted to a series of four test meals scheduled at a 1-wk interval. Although their prandial glycemia remained comparable with preprandial values for the first 16 min of the meals, insulinemia often exhibited early peaks (within a few min after meal onset) whose amplitude appeared related to palatability conditions. Evidence suggests that the insulin peaks triggered by cephalic stimulation are Pavlovian reflexes that become conditioned to the test situation. A typical neuroendocrine response to alimentary frustration is also described. The results are discussed in perspective with animal works, in terms of the effects of neuroendocrine events on feeding behavior.
Insulin infusion during a nocturnal fast suppresses the subsequent day-time intake.
Much recent evidence suggests a dual and opposite action of insulin on food intake and body weight. Peripherally administered, long acting insulin stimulates weight gain and food intake. On the contrary intracerebroventricularly infused insulin decreases food intake and body weight. It has been suggested that the shift from the nocturnal hyperinsulinism and hyperphagia to the day-time hypoinsulinism and hypophagia depended on the action of insulin on the brain during the night. It has also been hypothesized that the absence of nocturnal hyperinsulinism due to fasting was partly responsible for the hyperphagia observed during the subsequent day-time. In the present experiment, insulin was infused intravenously at various low doses (0.01, 0.025, 0.05 U/hr) during a nocturnal fast. Its effects on the following diurnal free food intake were investigated. It was shown that the experimentally elevated plasma insulin induced a dose-dependent reduction in the day-time feeding response. It was concluded that this reduction is due to the chronic action on the brain of the high plasma insulin level induced by the infusion during the nocturnal fast.
Meal to meal energy balance in rats.
Meal to meal energy balance was examined in thirty-eight simultaneous recordings of feeding pattern and O2 consumption in six rats. The mean difference between energy intake in a meal and energy expenditure until the onset of the next meal was found positive at night and negative during day time. At night the excess of meal intake over meal to meal expenditures was decreasing from the beginning to the end of the night and was strongly correlated to meal sizes. During day time meal to meal deficit was decreasing from the beginning to the end of the period but was not correlated to meal sizes. These meal location and size effects on the meal to meal energy balance were not determined by an effect of these factors on metabolic rate. No indication was provided that meal to meal energy balance was influenced by a "meal induced thermogenesis." Rather an evolution from the beginning to the end of the night of the correlation between meal size and durations of meal to meal intervals was found to be parallel to the evolution of positive meal to meal energy balance throughout the night. From these data it is concluded that at night a dual utilization of meal caloric intake (current energy metabolism plus fat storage) and a dual source of fuel during the day (food plus mobilized fats) determine time and mechanism of meal onset.
Sensory versus dietary factors in cafeteria-induced overweight.
Normal Wistar rats became hyperphagic and obese when presented with high-fat, high-sugar or "cafeteria" diets. This phenomenon could be due to the very palatability of the offered foods but a metabolic factor could be suspected. In an attempt to distinguish the effects of the nutritional characteristics from those of the sensory properties of food, a new cafeteria diet, the "isocafeteria" diet, was developed. It consists of a choice of foods of similar, well-balanced composition but varying in taste, smell and texture. It was confirmed that in normal Wistar rats, the high-fat and the traditional "cafeteria" diet led to extra-weight gain. It was demonstrated that the daily presentation of a new choice of the palatable foods which composed the "isocafeteria diet" led also to a sustained increase in food intake and to overweight. Variety and high palatability are per se sufficient factors to overcome regulatory mechanisms. It was shown that the metabolic efficiency of such a regimen was strikingly higher than those of high-fat and traditional cafeteria diets.
[Comparative effects of lesion of the basolateral nucleus and lateral nucleus of the amygdaloid body on neophobia and conditioned taste aversion in the rat].
The effects of bilateral lesions of the basolateral and lateral nuclei of the amygdala on the neophobic response and LiCl-conditioned taste aversion to a saccharin solution were studied in rats. Compared to intact animals, rats with basolateral lesions did not exhibit neophobia to the novel stimulus, while rats with lateral lesions demonstrated an initial preference to the sweet solution over water. The LiCl-induced aversion was suppressed after basolateral lesions and was unchanged after lateral lesions. It is concluded that these two amygdaloid nuclei play an important but distinct role in neophobia and conditioned taste aversion.
The effect of electrical stimulation of the hypothalamus on continuously-monitored blood glucose levels.
The effects of hypothalamic stimulation on blood glucose levels were investigated in unanaesthetised rats with intracardiac catheters directly connected to a continuous glucose analyzer. Thirty sec of low level electrical stimulation produced hyperglycemia at 23 of the 34 sites stimulated. At the remaining 11 sites the electrical stimulation produced no changes in blood glucose levels. The hyperglycemia could be dissociated from the changes in motor activity produced by the stimulation. The highest probability of producing hyperglycemia was found at ventro-lateral sites although hyperglycemia was also observed after stimulation of dorsal and medial sites. Apart from this medio-lateral difference in the density of sites at which stimulation produced hyperglycemia, the effects were not well differentiated anatomically. In addition, in terms of latency, peak magnitude and duration of the hyperglycemia, stimulation of the various hypothalamic subdivisions appeared to be functionally equivalent. Thus with respect to hypothalamic involvement in the maintenance of blood glucose levels the present stimulation analysis suggests a medio-lateral functional similarity which is very different from the medio-lateral reciprocity of lesion effects on ingestive behaviour and body weight.
Is regulation of body weight elucidated.
A new perspective on mechanisms involved in the regulation of a constant fat body mass and its relation to body energy balance is presented on the basis of a series of experiments. A study of the neuroendocrine conditions underlying the daily weight gain-weight loss cycle in rat and man and experimentally induced over and underweight, leads to the notion that lipogenesis and lipolysis above and below a range of physiological fluctuations of body fat develop a counter-regulatory tendency to correcting lipolysis and lipogenesis respectively. This development is attributed to a chronic central action of plasma insulin concentration on hypothalamic insulin receptors. This liporegulatory system which controls and regulates the filling and emptying of fat stores modulates the feeding system which controls and regulates the filling of a gastrointestinal store by eating and its emptying by metabolic food utilization.
Deprivation, palatability and the micro-structure of meals in human subjects.
Changes in the micro-structure of meals were studied in ten human subjects under different palatability and deprivation conditions. The oscillographic recording of chewing and swallowing movements during standardized meals allowed many meal parameters to be precisely measured. Both increases in deprivation time (from 4 to 15 h) and in food preference produce larger, longer meals. These factor's effects were additive. Eating rate was accelerated in high relative to low preference conditions. The micro-structure of meals proved to be more sensitive to food preferences than to deprivation levels: chewing activity per standard food piece tended to decrease as preference increased, as observed in a previous study. However, in the first quarter of meals, chewing time was affected similarly by deprivation and by preference. A clear deceleration of eating rate was apparent between the beginning and the end of meals. The results are discussed in perspective with other human studies and with reference to preference and deprivation as continua.