Effects of adrenal steroid agonists on food intake and macronutrient selection.

These experiments tested the effects of subcutaneous (SC) and paraventricular nucleus (PVN) administration of the steroid receptor agonists, corticosterone (CORT), aldosterone (ALDO), RU28362, and dexamethasone (DEX), on food intake and macronutrient selection during the first h of the dark feeding period in the rat. Results indicate that CORT and the selective type II receptor agonist RU28362 specifically stimulate carbohydrate ingestion after SC or PVN administration, while DEX has no effect on feeding. This selective effect of SC CORT on carbohydrate ingestion is dose dependent, seen at doses ranging from 0.125 to 2.0 mg/kg. Moreover, the stimulatory effects of CORT and RU28362 on carbohydrate intake are observed in ADX rats but not in sham rats. This is in contrast to SC and PVN administration of the type I receptor agonist ALDO, which specifically enhances fat ingestion in both sham and ADX rats. These results, with both peripheral and central steroid administration, reveal selective effects of type I and type II receptor stimulation on fat and carbohydrate intake, respectively.     

The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle.

Several reports indicate that central injection of galanin stimulates feeding, and that there is macronutrient specificity in this response. In addition, the galanin receptor antagonist, M40, reduces food intake when injected centrally. The nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (PBN) contain galanin receptors, and are involved in the control of food intake. Hence, we sought to compare the feeding response to galanin injection into these areas with that of third ventricle (3V) galanin injection. The feeding response to injection of galanin was greatest for the 3V. Hindbrain injection of galanin stimulated food intake only at the beginning of the dark period. NTS injection of M40 inhibited intake of a macronutrient diet in food-deprived rats, but was ineffective at reducing dark-onset feeding or deprivation-induced chow intake. 3V injection of M40 did not reduce deprivation-induced intake. PBN injection of galanin at dark onset had no effect in a group of fat-preferring rats. These results suggest that hindbrain galanin may contribute to feeding by inhibiting satiety, and that hypothalamic galanin receptors are involved with stimulation of intake. Furthermore, the absence of a consistent pattern of the stimulation of macronutrient intake suggests that galanin may not be a significant effector of macronutrient selection during individual meals.     

A moderate swimming exercise regularly performed throughout the life induces age and sex-related modifications in adaptive macronutrients choice

The ability of laboratory rats to adapt food intake to needs is well-known. The present study investigates changes in this adaptive behavior when animals grow old. A cohort of male and female Lou/c/jall rats was regularly submitted to an exercise throughout their life (6 consecutive days of moderate intensity training (3×15 min/day)). Caloric intake and macronutrients selection during exercise and post-exercise periods were compared to the pre-training period. During swimming, a decrease in both caloric intake and fat selection was observed and an increase in protein intake was specifically seen in female groups. However, males were unable to modify the diet composition (macronutrient rate) from 16 months of age, whereas females were able to do it until 24 months of age. The present results suggest a sex-dependant loss of capacity of adjusting feeding behavior to metabolic needs when animals grow old, may be due to a deterioration of the central control of food intake.     

Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions

Noradrenergic mechanisms of the hypothalamic paraventricular nucleus (PVN) have been shown to play an important role in the stimulation of feeding To determine the influence of this nucleus in monitoring and controlling responses to physiological and pharmacological challenges, PVN electrolytic lesion rats were tested for their behavioral responsiveness to agents known to affect the alpha-2 noradrenergic system as well as release of corticosterone, and to short- and long-term periods of food deprivation. Discrete lesions of the PVN produced enhanced feeding, particularly of carbohydrate, in freely-feeding rats maintained on a macronutrient self-selection paradigm. Lesion rats demonstrated a behavioral deficit in food intake regulation (a decrease in carbohydrate ingestion) in response to 5-hr and 24-hr fasts, showed a disturbance in circadian feeding, and exhibited a dramatic decrease in circulating corticosterone. However, feeding in response to 2-deoxy-D-glucose and insulin remained intact, suggesting that noradrenergic receptors within the PVN are not involved in the mediation of glucoprivic-induced feeding.     

Central administration of ghrelin preferentially enhances fat ingestion

Ghrelin, a brain-gut peptide discovered from the stomach, stimulates growth hormone release, food intake, adiposity, and weight gain. Circulating ghrelin levels are modulated under conditions of positive and negative energy balance, however its effect on macronutrient selection is not known. The present experiment investigates the effect of ghrelin on single and two-diet feeding paradigms in high-carbohydrate (HC) and high-fat (HF) preferring rats. In the macronutrient selection test in which rats were given free access to either high-carbohydrate or high-fat diet, an intracerebroventricular (i.c.v.) administration of ghrelin potently enhanced fat intake over carbohydrate intake in both HC- and HF-preferring rats. In the diet preference test in which rats were given free access to both high-carbohydrate and high-fat diets simultaneously, an i.c.v. administration of ghrelin also preferentially enhanced fat consumption over carbohydrate in both HF- and HC-preferring rats. Intracerebroventricular administrations of galanin and neuropeptide Y enhanced fat and carbohydrate ingestion, respectively. Centrally administered ghrelin enhanced fat ingestion. These results provide further insights for the role of ghrelin in feeding behavior and the development of obesity.     

Fluoxetine-maintained obese humans: effect on food intake and body weight

The effects of fluoxetine on food intake, body weight, and mood of obese individuals was examined in a 16-week inpatient/outpatient study. Six male and eight female obese volunteers began the study (four male and five females completed all phases of the study). They lived in a residential laboratory during three one-week inpatient periods separated by a 5-week and an 8-week outpatient period. Following an initial 4-day placebo baseline, participants were maintained on fluoxetine (60 mg/day) for the remainder of the study. Food intake parameters (total daily energy intake, macronutrient intake, mean number of eating bouts, interbout interval), body weight, subjective effects, and task performance were measured several times during the day during inpatient periods; food intake questionnaires were completed daily during the outpatient periods. Fluoxetine significantly reduced daily energy intake derived from fat, carbohydrate, and protein by decreasing the mean number of eating bouts per day throughout the study. No other food intake parameter was affected. Body weight was significantly reduced after 7 weeks, but not after 16 weeks of daily fluoxetine administration. These results indicate that fluoxetine reduced food intake for at least 16 weeks in nondepressed obese individuals without specifically affecting carbohydrate intake. Weight that was lost during the first few weeks of daily fluoxetine administration was subsequently regained even though food intake remained reduced. Therefore, fluoxetine maintenance does not appear promising as a sole long-term therapy for obesity.     

Macronutrient relationships with meal patterns and mood in the spontaneous feeding behavior of humans

The role of protein, carbohydrate and fat ingestion on self-rated mood and subsequent food intake was investigated using self-reports of spontaneous food intake. Eight male and 30 female undergraduate students were instructed to list everything they ate, when they ate it, and their mood at the time of ingestion. They were asked to make these entries in a diary throughout a nine day period. Mood was rated at the beginning of each meal on three seven point scales; elated-depressed, tired-energetic, and anxious-tranquil. The amount of protein, carbohydrate, and fat as well as the total amount of food energy in each meal and the intermeal intervals (IMIs) prior to and following the meals were calculated with a computerized analysis. The energy content and the amount of each of the macronutrients contained in the stomach at the beginning and end of each meal was estimated with a mathematical model. These data were then intercorrelated using bivariate and multivariate techniques. Momentary self-rated mood was not found to be related to prior macronutrient intake nor was it predictive of subsequent intake. Long term macronutrient intake, averaged over the nine recording days, was found to be related to the averaged mood of the subjects. Although no significant relationships were found between the absolute amounts of the macronutrients ingested and mood, significant correlations were found between the proportion of each macronutrient in the diet and the overall self-rated mood.(ABSTRACT TRUNCATED AT 250 WORDS)     

Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats

Neuropeptide Y (NPY), repeatedly injected in the hypothalamic paraventricular nucleus (PVN), produces dramatic obesity and overeating in female rats maintained on a single nutritionally complete diet. In the present study, we investigated whether these effects could also be obtained in animals with a choice of three pure macronutrients: protein, carbohydrate, and fat. Female rats with indwelling PVN cannulas were injected with NPY (235 pmol) or its saline vehicle every 8 hr for 6 days. A third group was left undisturbed. Consumption of each macronutrient and body weight were measured every 24 hr for 6 days preinjection, 6 days during injections, and 21 days after the injections were terminated. Relative to vehicle or preinjection rates of body weight gain (approximately 1.5 g/day), NPY dramatically enhanced weight gain to a rate of 9.3 g/day and more than doubled total daily food intake. This augmentation was accounted for by increases in carbohydrate intake (+26.4 kcal/day) and fat intake (+48.5 kcal/day), with no significant potentiation of protein consumption. When the NPY injections were terminated, body weight and macronutrient intake returned to control levels within 1 or 2 weeks. These findings are consistent with a role for NPY in hypothalamic mechanisms of macronutrient intake and body weight regulation and suggest that disturbances in brain NPY may contribute to the development of eating and weight disorders.     

Night and day: Diurnal differences in the behavioural satiety sequence in male rats

The behavioural satiety sequence (BSS) is an important method for assessing the selectivity of treatment (physiological, pharmacological and/or genetic) effects on food intake in rodents. The concept describes the natural progression from feeding to resting, with the transition between the two a useful biomarker of behavioural satiety. Although treatments can accelerate (anorexigenics) or delay (orexigenics) this transition without disrupting behavioural structure, the detection of such changes depends upon the timing of the transition under control conditions. Fasting and presatiation are known to affect this timing. However, recent observations in our laboratory have suggested that phase of testing (light or dark) might also be an important consideration. The present study therefore directly compared food intake and the BSS in thoroughly habituated male rats maintained either on a normal light cycle and tested during the light phase or on a reversed light cycle and tested during the dark phase. The results show that phase of testing had relatively little impact on food intake or diverse measures of ingestive and non-ingestive behaviour. Although modest differences were detected in locomotion, grooming and scratching (higher in dark phase), by far the largest difference concerned resting behaviour which had both a later onset and a much lower peak level during dark phase testing. Importantly, these behavioural differences delayed the transition between eating and resting. The potential contribution of diurnal differences in rate of eating is discussed as are the implications of these findings for future studies on the neurobiology of feeding behaviour.     

The satiety effects of intragastric macronutrient infusions in fatty and lean Zucker rats

To evaluate satiety in the hyperphagic, genetically obese Zucker “fatty” (fafa) rat, food-deprived fatty and lean (FaFa) control rats were given equicaloric intragastric infusions consisting largely of fat, carbohydrate, or protein. Relative to distilled water infusion, these infusions resulted in immediate reductions of food intake in both fatty and lean rats allowed to feed 20 min post-infusion. Cumulative food intakes remained reduced throughout the 2 hr period of observation. Thus, despite its hyperphagia, the fatty rat is responsive to the satiating effect of infused nutrients. However, the relative satiating effectiveness of the macronutrient infusions differed for the two genotypes. In lean rats, the different macronutrient infusions resulted in equivalent reductions of feeding. In contrast, in fatty rats, fat was the least satiating and protein was the most satiating macronutrient. Moreover, compared to lean rats, fatty rats displayed less initial suppression of feeding after fat infusion and greater overall suppression after protein infusion. These effects are consistent with the long-term feeding behavior of the fatty rat for the different macronutrients and may be related to pre- and postabsorptive metabolic alterations that have been documented in this animal.     

Effect of melatonin on total food intake and macronutrient choice in rats

Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10 000 and 15 000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a “night cue”, and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.     

Oral serotonin administration affects the quantity and the quality of macronutrients selection in European sea bass Dicentrarchus labrax L

Teleost fish are able to regulate their energy intake selecting from pure macronutrients sources, but the regulatory mechanisms involved in macronutrients selection remain unknown. Serotonin (5-HT) reduces food intake in mammals and fish and modifies the macronutrients selection pattern in mammals; however, no information is available about its role on macronutrients selection in fish. The aim was to determine the effect of orally administered 5-HT (0.1, 0.5 and 2.5 mg kg BW(-)(1)) into gelatine capsules on the subsequent macronutrient selection of sea bass, using for this purpose gelatine capsules including carbohydrates, protein, or lipids separately. The voluntary ingested 5-HT was released into the plasma of fish, reaching a level two times greater than the controls, 45 min after the ingestion of a capsule containing 2.5 mg kg BW(-1) of 5-HT. The indoleamine, at doses of 0.1, 0.5 and 2.5 mg kg BW(-1), produced a reduction in total food intake of 31%, 49% and 37%, respectively, compared to the baseline, modifying the macronutrient selection pattern. The percentage of fat selected was significantly reduced whereas the percentage of protein significantly increased after administration of highest dose, but no changes were observed in the proportion of carbohydrate for any 5-HT doses. In conclusion, oral administration of 5-HT affected both amount of food intake and pattern of macronutrients selected. This is the first evidence supporting a role of 5-HT as a neurohumoral mediator involved in macronutrients selection in fish.     

Galanin in the PVN increases nutrient intake and changes peripheral hormone levels in the rat

In self-selection feeding paradigms, rats display differential patterns of nutrient (protein, carbohydrate or fat) intake. Factors known to influence this selection include brain peptides as well as circadian parameters. In this series of experiments we investigated the role of PVN galanin in nutrient intake during the early and late dark periods in the rat. Rats were allowed to select between three isocaloric diets enriched in protein, carbohydrate or fat. Following a 2-week adaptation period, the animals' 24-h intake was monitored for 4 weeks. Galanin was injected into the PVN and food intake was measured 1, 2 and 24 h post-injection. Galanin significantly increased the 1 h total food intake but it failed to increase the intake of any particular nutrient. Galanin had no effect 2 or 24 h post-injection. Analysis of the data grouped by preference based on the rats 24 h baseline selection patterns over the 4-week period revealed that galanin seem to increase the preferred nutrient. That is, galanin preferentially increased the intake of the carbohydrate- or fat-rich diet in animals with high (over 40% of the total food intake) 24-h baselines in this particular nutrient. Finally, analysis of the plasma hormone levels after paraventricular galanin administration revealed a significant increase in noradrenaline levels, a small reduction in plasma insulin with no effects on adrenaline, glucose or corticosterone. The data revealed that galanin in the PVN influences both food intake and metabolic functioning. PVN galanin significantly increases sympathetic outflow and seems to stimulate the intake of the individual rat's preferred macronutrient.     

2-Deoxy-D-glucose and mercaptoacetate induce different patterns of macronutrient ingestion.

2-Deoxy-D-glucose (2DG) and mercaptoacetate (MA) are antimetabolic agents that reduce the metabolism of glucose and fatty acids, respectively, and stimulate feeding. The present study compared the effects of MA and 2DG on macronutrient self-selection. Because 2DG and MA have different metabolic actions and appear to activate different neural pathways, our hypothesis was that 2DG and MA would elicit different patterns of macronutrient selection. The first experiment examined macronutrient selection in response to 2DG, MA, and 0.9% saline in rats maintained on a three-macronutrient self-selection diet consisting of cornstarch, casein, and vegetable oil. Subsequently, one macronutrient source was replaced in each of three similar experiments with Polycose, albumin, or solid vegetable shortening. Finally, 2DG and MA tests were conducted in which only one macronutrient (cornstarch, casein, or oil) was available during the test. Results show that MA and 2DG elicit different macronutrient preferences. 2DG elicits intake of all three macronutrients in the same relative proportion consumed during spontaneous feeding across a number of dietary conditions, suggesting that glucoprivation activates interoceptive signals and neural pathways similar to those involved in normal hunger. MA elicits a selective intake of protein. Conditions in which carbohydrate palatability is enhanced or protein palatability is diminished lead to a relative increase in carbohydrate intake in response to MA. However, MA did not increase the intake of fat. Results suggest that intake of each macronutrient is subject to separate neural or endocrine control, and that these controls are linked to metabolic cues.     

2-deoxy-D-glucose inhibits food intake in rats after ventromedial hypothalamic lesions

Changes in food induced by 2 deoxy-D-glucose (2 DG) have been investigated in newly lesioned rats during the two parts of the diurnal cycle. In a first experiment rats were injected with saline or 2 DG (250, 500, 750 mg/kg) at the beginning of the light or the dark period. In a second experiment rats were injected with saline or 2 DG (250 mg/kg) in the middle of the two periods after 0, 2, 4 or 6 hr of fasting. Results show that 2 DG exerts an inhibitory effect on food intake at night, as it does in intact rats, under ad lib conditions or after a short deprivation time. The stimulating effects of 2 DG on diurnal food intake observed in intact rats is not replicated in VMH rats. On the contrary an inhibition of intake follows a short food deprivation. The data suggest that 2 DG stimulates food intake only under metabolic and feeding conditions characteristic of the diurnal phase in intact rats. Since lipogenesis and hyperphagia are observed 24 hr a day in VMH animals, only inhibition could follow 2 DG.     

Self-selecting albino rats exhibit differential preferences for pure macronutrient diets: Characterization of three subpopulations

Analyses of natural feeding behavior in albino male Sprague-Dawley rats demonstrate that, when allowed to self-select from pure macronutrient diets (protein, carbohydrate and fat), these rats of the same genetic strain can be categorized into 3 subpopulations according to either their 24-h or their 12-h nocturnal patterns of nutrient intake. A majority of the animals (HC for high carbohydrate, 50% of the total population) consumed a diet rich in carbohydrate relative to protein or fat, while a smaller population of rats (HF, 30%) preferred the fat diet, and an even smaller population (HP, 20%) chose a high-protein diet. These 3 subpopulations, after a few weeks of maintenance on the diets, differed in their body weight, with the HF rats having a higher body weight than the HP animals, who tended to weigh more than the lightest HC rats. Whereas all subgroups exhibited a similar bimodal distribution of feeding during the nocturnal cycle, with peaks during the early and late dark periods, they were distinguishable on the basis of their nutrient consumption during specific phases of the dark cycle. This difference was most apparent in the early dark phase, when the 3 subgroups exhibited exaggerated preferences for the specific nutrient that was generally preferred over the 24-h cycle. This is in contrast to the middle dark phase, when diet preferences were attenuated or lost, and the late dark phase, when most rats were similar in showing an increased preference for protein and fat and a decreased preference for carbohydrate. The HF group was further distinguished by an unusually strong burst of feeding during the first 2 h of the dark period and an extra peak of feeding in the middle dark period (7th h), both of which were relatively high in fat content.     

Effect of short-term fasting on macronutrient self-selection in sea bass

The influence of two different fasting periods on macronutrient self-selection during refeeding was studied in sea bass. Twelve groups of three sea bass were kept under laboratory conditions with a 12:12 light-dark cycle and at 22.5 degrees C. Each aquarium was provided with three self-feeders containing three different diets made up of two macronutrients: protein-fat, protein-carbohydrate, and carbohydrate-fat. The fish were allowed to acclimatise to the diets and laboratory conditions in 4 weeks, during which they selected a baseline diet of 51% protein, 16.5% carbohydrate, and 32.5% fat, in terms of digestible energy. The fish were then deprived of food for 6 days, after which they were permitted to refeed. When food demands stabilised, they were subjected to total food deprivation for another 2 weeks. The total energy demanded from all the macronutrients increased significantly during the first day after both fasting periods. The proportion of macronutrient self-selection after fasting periods remained unchanged in respect to the baseline, except for protein energy which remained high in the two first days of refeeding after the second fasting period (the 51% of total demanded energy from protein during the baseline period rising to 60%). In short, after two short fasting periods of different length, sea bass showed a compensatory ingestion of energy, with a slightly increased demand from protein after the longest fasting period.     

Feeding behavior responses of Zucker rats to naloxone

The effects of naloxone on feeding patterns were studied in both obese and lean Zucker rats during both light and dark phases of the diurnal cycle. Eight female obese (471±9 g) and lean (225±6 g) Zucker rats were trained to bar press for food. They were administered 0, 0.5, 1.0 or 2.0 mg/kg naloxone at the initiation of the light or dark phase of the diurnal cycle and feeding behavior was recorded for the subsequent 12 hr using an automated real-time data collection system. First meal size and duration were decreased and first postmeal interval was increased by naloxone and responses did not vary with phenotype or phase of the diurnal cycle. Naloxone decreased food intake during the 12-hr period by decreasing average meal size but meal frequency was not affected. Overall, the feeding behavior responses of obese rats to naloxone were greater than those of lean rats, supporting the hypothesis of an association between opioid peptides and obesity. Opioid involvement in diurnal control of food intake is also supported by the greater responses generally demonstrated in the light compared with dark phases.     

Fluid intake of rats in constant light and during feeding restricted to the light or dark portion of the illumination cycle

Rats restricted to eating and drinking during the light phase of a 12:12 light-dark (L-D) cycle (L-drinkers) consumed much smaller volumes of saccharin and NaCl than did rats whose feeding and drinking was restricted to the dark phase (D-drinkers). The patterns of fluid intake within the respective 12-hr feeding periods were markedly different for L- and D-drinkers and the food/fluid ratios were significantly lower for D- than for L-drinkers. It was concluded that illumination affects fluid intake independently of changes in food intake and that light limits the rat's capacity for fluid ingestion. L- and D-drinkers did not differ in their preference for saccharin over water in two bottle preference tests; this suggests that light does not interfere with the rat's ability to detect and determine the quality of the taste stimulus. Differences in ingestive behavior between L- and D-drinkers may in part reflect constraints imposed by changes in the sleep-wakefulness cycle. Intake of a wide concentration range of saccharin solutions was decreased in ad lib fed rats housed in constant light (L-L); differences in fluid intake between the L-L and L-D groups varied directly with the hedonic value of the saccharin solutions. Only 44% of rats housed in constant light as compared to 100% of rats maintained in a L-D cycle decreased their intake of a saccharin solution whose ingestion was followed by injection of lithium chloride. This finding is relevant to studies of illness-induced aversions and was related to circadian rhythms in drug susceptibility and their alteration in constant light. The necessity for controlling and specifying environmental illumination in studies of ingestive behavior was emphasized and various methodological considerations related to illumination cycles were discussed.     

Intraperitoneal leptin modifies macronutrient choice in self-selecting rats

This study aimed to evaluate the consequences on food intake and body weight (BW) of leptin administration in rats receiving a choice between the three macronutrients. Two studies were performed: during the first, rats received an acute intraperitoneal (IP) leptin administration (1 mg/kg) twice (at 8 and 14 weeks of age), at the beginning of the nocturnal cycle, while during the second, they received a chronic leptin infusion (osmotic minipump, 7 days). The total 24-h food intake after acute leptin injections was reduced by 14% and 17%, respectively. Body weight gain (BWG) after leptin injections was about half that seen on control days. Chronic leptin infusion reduced total intake, affecting mainly protein (P). Fat intake increased slightly since day 2 and became significant on the fourth day. After the leptin infusion, carbohydrate (CHO) eaters (>35% carbohydrate/total energy) significantly reduced the carbohydrate proportion in their total energy intake. There was no difference concerning macronutrient selection by fat eaters (Hfat). Leptin infusion reduced the number of mixed meals on the first day. In addition, the thermogenesis of brown adipose tissue (BAT) was higher in leptin than in control (C) rats. Consequently, leptin injections reduced food intake and BWG and increased thermogenesis, thus acting on the two terms of the energy balance. Moreover, leptin has different effects on macronutrient preferences, dependent upon age (tests 1 and 2) and the type (acute or chronic) of injection. High leptinemia level related to age or to minipump infusion lead to leptin resistance as found in old or obese subjects. It could explain our results.