J. Le Magnen

A fall in blood glucose level precedes meal onset in free-feeding rats

It has been suggested for a long time that the metabolic stimulation to eat or the hunger arousal of eating, originated from a fall in the blood glucose level induced by the periodic failure of hepatic glucose production to match the peripheral glucose uptake. However, this suggestion has not been substantiated directly by the results of periodic blood glucose evaluations performed during intermeal intervals in free-fed rats. In this experiment, a technique involving a continuous blood glucose determination over several hours was used in free-feeding, undisturbed rats. It was shown that all nocturnal and diurnal meals were preceded by a 6 to 8% fall of blood level, starting 5 to 6 min prior to meal onset. The overall consequences of these findings are discussed.

Metabolic correlates of the meal onset in the free food intake of rats

Abstract By recording the free feeding pattern of rats, a linear relationship between meal sizes and the time elapsed until the onset of a new meal had been previously found. This fact suggested that the onset of each meal and therefore the meal frequency were directly dependent on critical metabolic events. In order to test the new possibility so offered to elucidate further the nature of metabolic signals involved in the regulation of food intake, respiratory exchanges and free feeding patterns of rats were simultaneously recorded and analysed. In thirteen 24 hr cycles of ten rats metabolic rate, lipogenesis or lipolysis rates were compared to the concomitant rate of food intake in various fractions of time of the nycthemeral D-L cycles. It was found that habituated rats exhibited a cycle of nocturnal fat synthesis and diurnal fat mobilization. The rate of calories used for lipogenesis or supplied by lipolysis respectively added to or subtracted from the metabolic rate accounted for the high rate of food intake during the dark and its low rate during the light period. Some indications existed that in the nocturnal phase, a true and measured hyperphagia of normal rats was a primary cause of the concomitant lipogenesis and that in this period, the control of food intake either escapes entirely from metabolic influences or is affected, at a low threshold, by a relative shortage of the glucose availability for cell oxidation. In the light period, the onset of each meal occurred at a maximal rate of lipolysis and at a minimal rate of the contribution of other metabolites (essentially of glucose derived from ingested foods) to the metabolic rate. The pharmacological or hormonal inhibition of this diurnal lipolysis induced an immediate increase of the food intake through shortening of meal to meal intervals. These two facts, among others, provide evidence that, in the light period and by contrast to the night, the low rate of food intake results from the concomitant lipolysis and, that, in this period, the control system of food intake is responsive at a high threshold to a critical deficit of the availability of glucose for cell oxidation. Thus this availability of glucose is confirmed as a plausible stimulus to eat.

Pain modulating and reward systems: A single brain mechanism?

Abstract The hypothesis that brain rewarding and pain modulating systems could involve a common opiate system, identically blocked by naloxone, has been tested in three experiments. The preferences or aversions for sapid solutions in rats have been employed as reliable measures of responses to rewarding or nociceptive stimulations. In the first experiment, it was shown that the spontaneous aversion to a quinine HCl solution was enhanced when rats were offered the solution 30 min after naloxone at a dose of 1 mg/kg. The same enhanced aversion was observed in the second experiment towards a sweet solution previously made aversive through a conditioned taste aversion paradigm. In the third experiment, by using two different procedures and saccharin or glucose solutions, it was found that naloxone acutely abolished the preference for sweet solutions versus water in rats. It is concluded that: (1) the enhancement by naloxone of the aversion to a sapid solution, similar to the naloxone induced hyperalgesia, allows to assimilate this aversion to other responses to nociceptive stimulations; (2) this suggests that, like other responses to nociceptive stimulations, this aversion is normally attenuated through the release of brain or pituitary opiates; (3) the suppressant effect of naloxone upon both this attenuation of aversion and a preference for a sapid solution supports the notion of a biochemical and functional community between rewarding and pain modulating systems.

A selective control of olfactory bulb electrical activity in relation to food deprivation and satiety in rats

Abstract The possible role of centrifugal neural pathways in a feedback control of the olfactory input related to regulatory mechanisms of feeding behavior, has been investigated in rats. Bipolar electrodes were chronically and bilaterally implanted and multiunit discharges of the mitral cell layer recorded in unanesthetized rats. From the basal level of integrated activity, three types of responses to odor stimulations were considered: positive (enhanced), negative (inhibited) and null (unchanged). Rats were tested in a first group either hungry, after food deprivation or satiated, immediately after a single 2hr-daily meal. In a second group, they were tested either hungry under the effect of 20 U/kg body weight, of injected insulin, or satiated after their daily meal. In both groups, rats either hungry or satiated, were stimulated in test series by two different odors: (a) the odor of their familiar stock-diet; and, (b) a control odor: isoamyl acetate in the first group, citral in the second. Stimulated by the food odor, food-deprived and insulin treated rats exhibited positive responses. They exhibited, when satiated, significantly different negative responses. Stimulated by control odors, rats either hungry or satiated showed a same pattern of negative or null responses. Results are discussed in terms of a motivation dependant feedback control of the olfactory input in which the anatomically identified olfacto-hypothalamic loop is likely involved.

The structure of meals in humans: Eating and drinking patterns in lean and obese subjects

Abstract Lean and obese human subjects were observed during various single or mixed flavor meals of different palatability level. Chewing and swallowing responses were continuously recorded on an oscillograph, and a precise temporal analysis of their intrameal eating and drinking patterns was realized. Increasing palatability induced a decrease in chewing activity per food unit and, in the obese only, reduced the duration of intrameal pauses. In lean subjects, chewing time per food unit and intrameal pause duration increased from the beginning to the end of meals, probably due to developing satiation. Obese subjects appeared more stimulated than the lean at intermediate palatability levels. Prandial drinking occurred most often at the end of meals and may serve to enhance sensory stimulation. Mediation mechanisms are discussed.

Parameters of the meal pattern in rats: Their assessment and physiological significance

Parameters of the meal pattern in rats were assessed and their physiological significance investigated through a detailed study of continuous graphic recordings over 20 consecutive days in ten rats. Both prandial and diurnal periodicities were examined. The definition of meals, by a criterion of 40 min of non-eating before and after a feeding episode, was validated statistically. The two superimposed periodicities were substantiated by studying night and daytime differences in meal sizes, meal-to-meal intervals, meal size/interval ratios, and post prandial correlations. The results provide new evidence for the role of metabolic and neuroendocrine factors in determining the relationships between meal size and post-meal intervals and their differences during the two parts of the diurnal cycle.

Palatability and preabsorptive insulin release.

The purpose of these experiments was to determine whether the level of orally-triggered and vagally-mediated preabsorptive insulin release was related to the degree of food palatability as measured by the amount of food necessary to produce satiation. Rats were habituated to a feeding schedule of five meals per day. During a test meal they were presented with one of 3 forms of their regular diet: unaltered, sweetened with Sucaryl sodium or adulterated with quinine hydrochloride. From 1.5 min preceding the meal to 19.5 min later, blood was continuously drawn via a chronic intravenous catheter. Blood was collected for regular intervals and immunoreactive insulin levels were determined. During the test meals, the rats ate 3, 4.9 and 1.5 g of the three diets, respectively. Within the first 3 min following meal onset, they exhibited a peak insulin release of 47, 65 and 25 microU/ml, respectively. Since this early insulin response disappeared long before the end of the meal, it was suggested that the palatability-dependent amount eaten could be affected by the palatability-modulated preabsorptive insulin release.

The analysis of human feeding patterns: the edogram.

Normal-weight subjects were presented with various single- or mixed-flavour meals of different palatability levels. Their chewing and swallowing movements were continuously recorded on an oscillograph and the resulting graphs, the “edograms”, allowed a precise temporal analysis of the eating sequences. Increasing palatability induced an increase in meal size and duration, and a decrease of such parameters as chewing time and number of chewing movements per food unit. Chewing time per food unit and interval between food units increased from the beginning to the end of the meals, probably due to growing satiation. These observations confirm the edogram as a useful tool for the study of food motivation.

Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate.

The effect of taurine derivative, Ca-acetyl homotaurinate, on voluntary alcohol intake was investigated in ethanol-dependent and naive rats. A high 24 hr oral intake of a 10% ethyl alcohol solution (9-10 g/kg) was exhibited by rats following 15 days of intragastric infusions of ethanol (7-8 g/kg/day). In four groups, rats were IG injected by short pulses of isotonic saline or a daily dose of 200, 300 and 450 mg/kg respectively, distributed over six daily infusions during alternating 8 hr presentations of ethanol solution and water. Compared to their respective basal intakes during the first two days of injection, the rats demonstrated a dose-dependent 50 to 70% reduction in alcohol consumption with drug treatment. This suppression effect was specific to the ethanol solution and persisted during 4 days of post-treatment observation. In ethanol-naive rats similarly tested and drinking half the amount of alcohol drunk by their ethanol-dependent counterparts, only the highest dose of drug (450 mg/kg) significantly suppressed their alcohol intake. It is suggested that Ca-acetyl homotaurinate interacts with CNS mechanisms involved in the ethanol tolerance-dependence state, underlying an enhanced reinforcing property of ethanol oral intake. Opioid receptors could be the targets in this action.

Deprivation, paiatability 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 factors 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.