Nighttime Food Intake Research Articles

A single-arm pilot study: can a parental sleep intervention for sleep-disturbed young children in individual settings improve children’s sleep, crying, eating, and parental distress in mothers and fathers?

BackgroundEarly sleep problems co-occur with crying, eating problems, and parental distress. This study investigates the impact of a parent-focused intervention to improve child sleep with the following aims: (1) To assess the impact on child sleep (sleep onset latency, frequency and duration of nighttime awakenings, frequency of bed-sharing, and nighttime food intake, total nighttime sleep duration, and sleep efficiency), child crying (frequency of crying episodes, of unexplained and unsoothable crying and of crying out of defiance), child eating difficulties, and parental distress of mothers and fathers. (2) To assess the maintenance of any changes in these areas longitudinally, at 3-month, 6-month, and 12-month follow-ups. (3) To explore at the within-subjects level, how children’s sleep, crying, eating, and parental distress changed together across all study measurement points.MethodsIn this single-arm pilot study, the parents of 60 children participated in six individual sessions of a parent-focused multimodal age-adjusted cognitive-behavioral intervention to improve child sleep. Parents of 39 children (46% girls, age in months M = 22.41, SD = 12.43) completed pre- and at least one measure after the intervention. Sleep diary, questionnaire for crying, feeding, sleeping, and parental stress index (short-form) were assessed pre, post, three, six, and 12 months after the intervention.ResultsSignificantly, sleep (decreased sleep onset latency, frequency, duration of nighttime awakenings, bed-sharing, nighttime food intake; increased total nighttime sleep duration, sleep efficiency), crying (reduced frequency of crying episodes, unexplained and unsoothable crying), and parental distress (reduced) changed, which remained partially stable over follow-up. The frequency of crying episodes decreased with fewer nighttime awakenings; morning crying with increased nighttime feeding; unexplained and unsoothable crying with higher sleep efficiency; crying due to defiance with more nighttime awakenings, sleep efficiency, and bed-sharing. Eating problems decreased with shorter night awakenings and time; maternal distress with fewer nighttime awakenings, paternal with less child’s nighttime feeding, unexplained and unsoothable crying, and time.ConclusionsA parental sleep intervention for sleep-disturbed young children could be promising to reduce children’s sleep problems, crying, eating problems and parental distress. Future studies should consider more personal contact during the follow-up to reduce the drop-out rate and a randomized-controlled design.Trial registrationThe study was retrospectively registered at the German Clinical Trials Register (ID: DRKS00028578, registration date: 21.03.2022).

Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome

Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.

Tu2016 Establishment of a Novel Automated Method to Assess the Food Intake Microstructure in Rats

Background: Food intake is a parameter frequently assessed in rodent models. The classical approach is to measure food intake manually after defined time intervals. Although this technique is easy to learn and use, it holds several disadvantages: the animals are disturbed by the investigator, a real assessment of dark phase feeding is not possible, the measurement is rather rough as short-lasting effects may be missed and lastly, there is no information on the underlying feeding microstructure. Therefore, several approaches have been undertaken in order to assess this feeding microstructure including the use of liquid, powder or micropelleted food, which, however, does not represent the physiological solid food of rats. Aim: To evaluate an automated method to assess the physiological feeding microstructure in rats. Methods: Male Sprague Dawley rats were used and food intake was monitored manually and in an automated fashion using an automated episodic feeding monitoring system recently established for the use in mice (BioDAQ, Research Diets). In a separate experiment, intracerebroventricularly (ICV) cannulated rats were compared to naive rats (n=8/group). Results: Rats showed a linear daily body weight gain when housed in groups (3.1±1.5g) which did not significantly change directly after separation into single housing cages with feeding from the cage top (3.6±1.3g) or from the hopper of the automated monitoring device (2.7±0.1g, P=0.81). Also, the nighttime food intake, the period of the maximum food intake in rodents, was similar when assessed by the automated system on day 1 and 5 after starting the measurement (17.7±0.8 vs. 19.1±0.7g, P=0.24), indicating a rapid accommodation to this feeding device. In addition, daily food intake did not differ when assessed manually or in an automated fashion (21.9±0.4 vs. 21.1±0.2g, P=0.17), indicating a good concordance between both methods. The automated assessment allowed the measurement of parameters of the food intake microstructure, namely latency to first meal, inter-meal interval, meal size, duration and frequency, eating rate and the satiety ratio. The investigators observed the satiety sequence of rats in the automated feeding cages with a decrease in dark phase feeding behavior and an increase in grooming, exploration and resting indicating a physiological behavior. Lastly, in cages with an enlarged opening of the cage mount, ICV cannulated rats showed a similar dark phase food intake as naive rats (16.6±0.6 vs. 16.4±0.5g, P=0.86), indicating that the system can also be used in head device-bearing rats. Conclusions: The automated feeding monitoring device allows a detailed assessment of the food intake microstructure in undisturbed rats housed in regular cages and fed physiological rat chow. Therefore, this device will be a valuable tool in behavioral studies investigating food intake.

Tu2019 Role of Vitamin D in the Inflammatory Response of Morbidly Obese Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)

Background: Food intake is a parameter frequently assessed in rodent models. The classical approach is to measure food intake manually after defined time intervals. Although this technique is easy to learn and use, it holds several disadvantages: the animals are disturbed by the investigator, a real assessment of dark phase feeding is not possible, the measurement is rather rough as short-lasting effects may be missed and lastly, there is no information on the underlying feeding microstructure. Therefore, several approaches have been undertaken in order to assess this feeding microstructure including the use of liquid, powder or micropelleted food, which, however, does not represent the physiological solid food of rats. Aim: To evaluate an automated method to assess the physiological feeding microstructure in rats. Methods: Male Sprague Dawley rats were used and food intake was monitored manually and in an automated fashion using an automated episodic feeding monitoring system recently established for the use in mice (BioDAQ, Research Diets). In a separate experiment, intracerebroventricularly (ICV) cannulated rats were compared to naive rats (n=8/group). Results: Rats showed a linear daily body weight gain when housed in groups (3.1±1.5g) which did not significantly change directly after separation into single housing cages with feeding from the cage top (3.6±1.3g) or from the hopper of the automated monitoring device (2.7±0.1g, P=0.81). Also, the nighttime food intake, the period of the maximum food intake in rodents, was similar when assessed by the automated system on day 1 and 5 after starting the measurement (17.7±0.8 vs. 19.1±0.7g, P=0.24), indicating a rapid accommodation to this feeding device. In addition, daily food intake did not differ when assessed manually or in an automated fashion (21.9±0.4 vs. 21.1±0.2g, P=0.17), indicating a good concordance between both methods. The automated assessment allowed the measurement of parameters of the food intake microstructure, namely latency to first meal, inter-meal interval, meal size, duration and frequency, eating rate and the satiety ratio. The investigators observed the satiety sequence of rats in the automated feeding cages with a decrease in dark phase feeding behavior and an increase in grooming, exploration and resting indicating a physiological behavior. Lastly, in cages with an enlarged opening of the cage mount, ICV cannulated rats showed a similar dark phase food intake as naive rats (16.6±0.6 vs. 16.4±0.5g, P=0.86), indicating that the system can also be used in head device-bearing rats. Conclusions: The automated feeding monitoring device allows a detailed assessment of the food intake microstructure in undisturbed rats housed in regular cages and fed physiological rat chow. Therefore, this device will be a valuable tool in behavioral studies investigating food intake.

Prevalence and clinical characteristics of unremembered nocturnal eating in diabetic subjects: Kurume sleep trouble in obesity and metabolic disorders (KUSTOMED) study

Nighttime food intake is associated with weight gain and higher HbA1c levels. We experienced night eaters who have no memory of their nocturnal eating in the morning. In this study, the curious night eating behavior was designated as "unremembered nocturnal eating syndrome (UNES)". We screened 1,169 patients with diabetes for sleep quality and abnormal eating behavior at night using the Pittsburgh Sleep Quality Index questionnaire with an additional question regarding UNES. When abnormal nocturnal eating behavior was noted, detailed clinical information was extracted from interviews with the patients. We identified 9 patients who experienced UNES. They had a higher BMI compared with subjects who reported no such episodes. Among them, 6 patients who consumed food at night without memory 2-5 times per month or more had significantly higher HbA1c levels. Continuous glucose monitoring in a patient with type 1 diabetes revealed an abrupt elevation of glucose levels from midnight when some foods were consumed. Eight of the 9 patients were taking benzodiazepine and/or non-benzodiazepine hypnotic agents when they experienced the episodes. The prevalence of UNES was 0.8% in all subjects and 4% in those taking hypnotic drugs. The ratio of hypnotic drug use in subjects with UNES was significantly higher than for individuals without UNES (89% vs. 17%, p<0.0001). Although UNES seems to be etiologically heterogeneous, hypnotics-induced parasomnia and/or anterograde amnesia may be associated with the behavior. UNES is not rare in diabetic patients on hypnotic medicine and may be a hidden cause of unexpected morning hyperglycemia.

The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice.

Hemopressin is a short, nine amino acid peptide (H-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His-OH) isolated from rat brain that behaves as an inverse agonist at the cannabinoid receptor CB(1), and is shown here to inhibit agonist-induced receptor internalization in a heterologous cell model. Since this peptide occurs naturally in the rodent brain, we determined its effect on appetite, an established central target of cannabinoid signaling. Hemopressin dose-dependently decreases night-time food intake in normal male rats and mice, as well as in obese ob/ob male mice, when administered centrally or systemically, without causing any obvious adverse side effects. The normal, behavioral satiety sequence is maintained in male mice fasted overnight, though refeeding is attenuated. The anorectic effect is absent in CB(1) receptor null mutant male mice, and hemopressin can block CB(1) agonist-induced hyperphagia in male rats, providing strong evidence for antagonism of the CB(1) receptor in vivo. We speculate that hemopressin may act as an endogenous functional antagonist at CB(1) receptors and modulate the activity of appetite pathways in the brain.

Nighttime eating: commonly observed and related to weight gain in an inpatient food intake study

Background: Nighttime food intake has rarely been studied in inpatient settings and only one study observed a relation between self-reported nighttime eating and weight gain.Objective: We investigated the prevalence of nighttime eating and its effect on weight change.Design: Healthy nondiabetic Pima Indians (n = 117; 67 M, 50 F) and whites (n = 43; 29 M, 13 F) were admitted to a clinical research unit. After consuming a standardized diet for 3 d, participants ate ad libitum from a computer-operated vending machine that recorded the time of food selection. Energy intake was calculated as mean kcal/d. Follow-up weight was available for 94 volunteers.Results: Fifty-five subjects (36%) were nighttime eaters (NEs; persons who ate between 2300 and 0500 on ≥1 of the 3 d). Prevalence was similar among whites and Pima Indians (37% and 35%, respectively). There were no significant differences in body mass index or percentage body fat between NEs and non-NEs. NEs consumed more calories per day (4758) than did non-NEs (4244; P = 0.02), but the percentage of calories from macronutrients did not differ. NEs consumed ≈15% (690 kcal) of their daily energy during nighttime episodes. After control for baseline weight and follow-up time (x̄ ± SD: 3.4 ± 1.8 y), NEs (n = 29) gained more weight (6.2 kg) than did non-NEs (n = 65; 1.7 kg; P = 0.03).Conclusions: Nighttime eating was common, and it predicted weight gain. It remains to be determined whether this behavior indicates abnormal sleep patterns leading to nighttime wakefulness and food intake in those prone to weight gain.

Thermoregulatory, motor, behavioural, and nociceptive responses of rats to 3 long-acting neuroleptics

We investigated physiological effects of intramuscular injections of the following 3 long-acting neuroleptics commonly used in wildlife management: haloperidol (0.05, 0.1, and 0.5 mg/kg body mass), zuclopenthixol acetate (0.5, 1, and 5 mg/kg), and perphenazine enanthate (1, 3, and 10 mg/kg), in a rat model. Body temperature and cage activity were measured by intra-abdominal telemeters. Nociceptive responses were assessed by challenges to noxious heat and pressure. Haloperidol (0.5 mg/kg) produced a significant nocturnal hypothermia (p < 0.05) and decreased nighttime cage activity and food intake. Zuclopenthixol (5 mg/kg) significantly decreased nighttime body temperature and cage activity and, at 1 mg/kg and 5 mg/kg, significantly decreased food intake 5-17 h after injection (p < 0.05). Perphenazine (10 mg/kg) significantly decreased nighttime body temperature and cage activity and, at all doses, significantly decreased food intake 5-17 h after injection (p < 0.05). Significant analgesic activity was evident in rats given 5 mg/kg zuclopenthixol up to 40 h after injection, and 10 mg/kg perphenazine from 48 to 96 h after injection (p < 0.0001). Zuclopenthixol (5 mg/kg) and perphenazine (10 mg/kg) had significant antihyperalgesic activities at 16 h postinjection and 24-48 h postinjection, respectively (p < 0.0001). Haloperidol had no significant antinociceptive activity at doses tested. Motor function was impaired in rats given 0.5 mg/kg haloperidol, 5 mg/kg zuclopenthixol and 10 mg/kg perphenazine. Effects of long-acting neuroleptics on body temperature, feeding, and activity were short-lasted and should not preclude their use in wildlife. Antinociceptive actions were longer-lasting, but were nonspecific, and we recommend additional analgesics for painful procedures during wildlife management.

Metabotropic Glutamate Receptor mGlu5 Is a Mediator of Appetite and Energy Balance in Rats and Mice

The metabotropic glutamate receptor subtype mGlu5 modulates central reward pathways. Many transmitter systems within reward pathways affect feeding. We examined the potential role of mGlu5 in body weight regulation using genetic and pharmacological approaches. Adult mice lacking mGlu5, mGluR5-/-, weighed significantly less than littermate controls (mGluR5+/+, despite no difference in ad libitum food intake. After overnight food deprivation, mGluR5-/- mice ate significantly less than their mGluR5+/+ controls when refeeding. When on a high fat diet, mGluR5-/- mice weighed less and had decreased plasma insulin and leptin concentrations. The selective mGlu5 antagonist MTEP [3-[(2-methyl-1,3-thiazol-4-yl)-ethynyl]-pyridine; 15 mg/kg s.c.] reduced refeeding after overnight food deprivation in mGluR5+/+, but not mGluR5-/- mice, demonstrating that feeding suppression is mediated via a mGlu5 mechanism. MTEP (1-10 mg/kg) decreased night-time food intake in rats in a dose-related manner. At 10 mg/kg, MTEP injected at 8.5, 4.5, or 0.5 h before refeeding reduced overnight food intake by approximately approximately 30%. Diet-induced obese (DIO) and age-matched lean rats were treated for 12 days with MTEP (3 or 10 mg/kg/day s.c.), dexfenfluramine (3 mg/kg/day s.c.), or vehicle. Daily and cumulative food intakes were reduced in DIO rats by MTEP and dexfenfluramine. Weight gain was prevented with MTEP (3 mg/kg), and weight and adiposity loss was seen with MTEP (10 mg/kg) and dexfenfluramine. Caloric efficiency was decreased, suggesting increased energy expenditure. In lean rats, similar, although smaller, effects were observed. In conclusion, using genetic and pharmacological approaches, we have shown that mGlu5 modulates food intake and energy balance in rodents.

Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight

Orexins are recently identified neuropeptides, and have been shown to increase food intake when administered intracerebroventricularly. We examined the effects of chronic administration of orexin in rats by continuous intracerebroventricular administration by means of an osmotic minipump. Continuous administration of orexin-A (0.5 nmol/h) for 7 days in rats resulted in a significant increase in food intake in the daytime. Daytime food intake increased to 180% of the control value. However, it resulted in a slight decrease nighttime food intake as compared with vehicle-treated rats. The total amount of food intake per day was almost comparable with that of vehicle-administered rats. The gain of body weight and blood glucose, total cholesterol and free fatty acid levels were normal. Chronic orexin-A treatment did not cause obesity in rats. We observed abnormal behavior during the daytime after starting administration of orexin-A; these rats kept awake during the daytime. Our present observation showed that continuous administration of orexin-A could not overcome the regulation of energy homeostasis and body weight. However, orexin-A might be implicated in short-term, immediate regulation of feeding behavior.

Recombinant CART peptide induces c-Fos expression in central areas involved in control of feeding behaviour

We have recently shown that the hypothalamic neuropeptide CART (cocaine-amphetamine-regulated-transcript) is a leptin dependent endogenous satiety factor in the rat. In the present study we confirm and extend our previous observations by showing that intracerebroventricular (i.c.v.) administered CART(42–89) dose-dependently inhibits 3-h food intake in food restricted rats with a lowest effective dose of 0.5 μg. CART also potently inhibits NPY-induced food intake in satiated rats as well as nighttime food intake in free feeding animals. To identify brain areas potentially involved in mediating the anorectic effects of CART, the temporal expression pattern of the immediate early gene c- fos was examined in the central nervous system by immunohistochemistry in rats receiving recombinant CART. Compared to vehicle, CART induced c-Fos expression in several hypothalamic and brainstem structures implicated in the central control of food intake. In the hypothalamus, high numbers of c-Fos immunoreactive (-ir) cells were observed in the medial parvocellular part of the paraventricular nucleus and in the posterior part of the dorsomedial nucleus. Lower numbers of c-Fos positive nuclei were found in the supraoptic and arcuate nuclei. A relatively high number of c-Fos-ir cells was found in the central nucleus of the amygdala. In the brainstem, c-Fos-positive nuclei were found in the parabrachial nucleus, and in the nucleus of the solitary tract. Notably both the area postrema and the dorsal motor nucleus of the vagus were virtually devoid of c-Fos-ir cells. The present experiments suggest that CART peptide exerts its inhibitory effects on appetite by activating hypothalamic and brainstem neurones implicated in the central control of feeding behaviour and metabolism.

Effects of Lentinan on Abnormal Ingestive Behaviors Induced by Tumor Necrosis Factor

Tamura, R., K. Tanebe, C. Kawanishi, K. Torii and T. Ono. Effects of lentinan on abnormal ingestive behaviors induced by tumor necrosis factor. Physiol Behav 61 (3) 399–410, 1997.— Lentinan (LNT), a β-glucan derived from Lentinus edodes (Berk.) Sign., is known to work positively against cachexia in patients with malignant tumors. Because the cachectin/tumor necrosis factor (TNF) is supposed to be one of the factors that mediate cancer cachexia, we tested the effects of LNT on TNF-induced cachexia in rats. First, we analyzed in detail the cachectic actions of TNF (0.2 mg/kg/day, 5 days, IV) on food and water intake, body weight, and locomotor activity. The day after the first administration of TNF (acute phase), food and water intake, as well as body weight, of all rats decreased. However, over the next few days of treatment (chronic phase), the rats gradually developed a tolerance to the cachectic actions of TNF. Specifically, after the third administration, the rats treated with TNF had a higher amount of water intake than the control rats. This was mainly due to an increase in daytime water intake. We also analyzed the effects of LNT (0.1 or 1.0 mg/kg, twice/wk, IV) on TNF-induced cachexia, and compared the data with those from the rats treated with TNF alone. The higher dosage of LNT significantly suppressed TNF-induced daytime polydipsia and increased the amount of nighttime water intake, as well as the meal size of nighttime food intake. These results suggest that LNT partially normalizes TNF-induced cachexia in rats.

Antisense oligodeoxynucleotides to G-protein alpha-subunit subclasses identify a transductional requirement for the modulation of normal feeding dependent on G alpha OA subunit.

A variety of G-protein-coupled receptors are proposed to participate in the modulation of ingestive behavior and in the mode of action of antiobesity drugs. In the present study, we investigated the involvement of G-protein alpha-subunit subclasses (molecular transducers of multiple chemical signals) in the control of ingestive behavior. We report here that the chronic intracerebroventricular (i.c.v.) microinfusion for 72 h (via osmotic minipumps) with antisense phosphothio-oligodeoxynucleotides corresponding to G-protein alpha-subunitO common (to OA and OB) and OA subclasses decrease the nighttime food intake without affecting water intake in rats. Computerized analyses of the microstructure of feeding indicate that the G alpha OA antisense depresses feeding by reducing meal frequency, while meal size and meal duration increased slightly, but not significantly. The effects of G alpha O common and G alpha OA antisense on feeding are specific since the chronic i.c.v. microinfusion of sense to G alpha O common or G alpha OA, antisense to the related subclass G alpha OB, and antisense to other G-protein alpha-subunits (G alpha S, G alpha Q, G alpha 11 and G alpha i common) had no effect on food or water intake. The observed effects by G alpha O common and G alpha OA antisense imply a direct action in the central nervous system since the chronic subcutaneous microinfusion of G alpha O common and G alpha OA antisense in doses equivalent to two-fold higher relative to those administered centrally had no effect on food intake. The chronic microinfusion of G alpha O common antisense drastically decreased the levels of G alpha O protein detected in immunoblots of hypothalamic ventromedial nuclei. The results suggest that the G-protein alpha-subunit subclass G alpha OA is critical for the integrative modulation of normal feeding behavior, and that changes in its activity may be associated with modifications of feeding. These studies also show a novel approach to study the molecular basis of specific behaviors by manipulating elements of the transductional systems.

The Relationship Between Daytime and Nighttime Food Intake in an Obese Night‐Eater

Some obese individuals consume food during awakenings from nighttime sleep. Three studies were conducted on a 28-year-old morbidly obese male with chronic sleeping complaints and insignificant weight loss, despite self-reported daily caloric restriction: I. For 3 mo, the subject recorded food intake for 24-h periods. Mean daytime intake was 1286 kcal +/- 386 (SD), and mean nighttime intake was 1036 kcal +/- 487 (SD). Caloric values of daytime and nighttime intake were negatively correlated, r = -0.22, df= 82, p < .05. II. Seven consecutive 24-h food intake recordings were obtained with an automated formula dispenser when the subject was an inpatient on a metabolic ward and received ad libitum formula as his sole food source. Mean daytime intake was 1245 +/- 662 (SD), and mean nighttime intake was 231 +/- 236 (SD). There was a non-significant negative correlation between daytime and nighttime intake, r = -0.32, df = 5, NS. III. The subject underwent polysomnographic studies on 2 non-consecutive nights, following the administration of either a low (600 kcal) or high (1800 kcal) daytime caloric condition. The subject, upon awakening from nighttime sleep, could eat from a platter of sandwich quarters placed at his bedside. The addition of 1200 kcal to daytime intake decreased nighttime intake by 654 kcal, or by 55% of the additional calories delivered during the day. The three studies (I, II, and III) show that daytime food intake can be negatively correlated with nighttime intake, and that daytime intake can influence nighttime intake in a documented obese night-eater.

Interleukin-8 modulates feeding by direct action in the central nervous system.

Interleukin-8 (IL-8) is released in response to infection, inflammation, and trauma. The most important stimuli for IL-8 release during these pathological processes are IL-1, tumor necrosis factor, and bacterial lipopolysaccharide (endotoxin), factors that have been shown to suppress feeding. In the present study, the participation of IL-8 on the central regulation of feeding was investigated. Intracerebroventricular (icv) microinfusion of recombinant human IL-8 (rhIL-8, 1.0-100 ng/rat) suppressed the short-term (2-h) food intake. The most effective dose of rhIL-8, 20 ng, decreased 2-h food intake by 25% and nighttime food intake by 23%. Intracerebroventricular microinfusion of anti-rhIL-8 antibody (200 and 500 ng) blocked the effect of 20 ng rhIL-8 on 2-h and nighttime food intakes. Computerized analysis of behavioral patterns for the 2-h period demonstrated a specific reduction of meal size (by 33%), whereas meal frequency and meal duration were not affected after the icv microinfusion of 20 ng rhIL-8. This short-term food intake suppression by icv rhIL-8 was accompanied by a small, but significant, increase in cerebrospinal fluid-brain and rectal temperatures. Intraperitoneal administration of rhIL-8 in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IL-8 acts directly in the central nervous system to decrease feeding. This effect of IL-8 may contribute to the food intake suppression frequently accompanying pathological processes.

Chronic intrahypothalamic infusions of insulin or insulin antibodies alter body weight and food intake in the rat

In Experiment 1, one-week infusion of insulin (0.15, 1.5, or 15.0 μU/hr) into the ventromedial hypothalamus (VMH) of rats reduced body weight (BW) and nighttime food intake (FI). While 0.15 μU/h decreased daytime FI, 1.5 μU/h increased daytime FI and 15.0 μU/h left daytime FI unchanged. Total daily FI was decreased by the two highest doses. In Experiment 2, intra-VMH infusion of specific insulin antibodies (1.5 μUeq/h) increased BW and FI, while C-peptide antibodies were ineffective. In Experiment 3a, intracerebroventricular infusions of insulin failed to decrease FI and BW comparably to similar intrahypothalamic infusions. In Experiment 3b, intra-VMH insulin was infused via cannulae that bypassed the cerebral ventricles. The decrease in FI and BW was comparable to that observed when insulin was infused via cannulae that penetrated a ventricle. Histology from animals used in Experiments 1–3 indicates that optimum sites for insulin-induced changes in BW and FI in the hypothalamus lie in an area that includes portions of the paraventricular, arcuate, dorsomedial, and ventromedial nuclei.

Dexamethasone inhibits food intake suppression induced by low doses of interleukin-1 β administered intracerebroventricularly

Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1β (rhIL-1β, 0.125 to 2.0 ng/rat) dose-dependently suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. ICV infusion of bovine serum albumin (BSA), or heat-treated rhIL-1β had no effect on food intake. Pretreatment with dexamethasone (200 μg/rat, intraperitoneal) blocked the food intake suppression induced by low doses of rhIL-1β. This ability of dexamethasone, a synthetic corticosteroid, may have potential therapeutic implications in acute and chronic pathological processes associated with increased levels of IL-1 and appetite suppression.

Dual 24-hour feeding response to 2DG in rats: daytime increase and nighttime decrease.

Thirty-six rats were injected IP with 2DG (0, 250, or 500 mg/kg) at 7-day intervals, once at light onset (7 a.m.) and once at dark onset (7 p.m.), and postinjection food intake was monitored for 24 hours. Five hundred mg/kg 2DG caused food intake to rise above control levels during the first 6 hours of daylight, regardless of whether the injection had occurred that morning or the previous evening, whereas intake during the first 6 hours of darkness was consistently below control levels. In a second study, 24 rats were injected first at 7 a.m. (500 mg/kg 2DG or saline), and 7 days later at 7 p.m. (opposite drug), and food was withheld 12 hours until the light:dark period had changed. For 12 hours after food was returned, 2DG again decreased nighttime food intake (Injection 1) and increased daytime intake (Injection 2). 2DG's dual long-term effects cannot be accounted for either by malaise or by an initial action that later is compensated by its opposite. Rather, 2DG (500 mg/kg) appears to exert two independent, opposite alimentary effects which persist 18-24 hours and which change direction with phase changes in the light:dark cycle.

Food intake suppression by growth factors and platelet peptides by direct action in the central nervous system.

Intracerebroventricular (i.c.v.) microinfusion of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and platelet factor 4 (PF4) suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. I.c.v. infusion of platelet-derived growth factor (PDGF) suppressed only 2 h food intake. I.c.v. infusion of bovine serum albumin (BSA), nerve growth factor (NGF), or inactivated EGF, bFGF and PF4 had no effect. Intraperitoneal (i.p.) administration of EGF, bFGF, PF4 and PDGF in doses equivalent to or higher than those administered centrally had no effect. The results suggest a central action of growth factors and platelet peptides on feeding regulation.

Dependence of food intake on acute and chronic ventricular administration of insulin

Several lines of evidences indicate that insulin affords short- and long-term neuroendocrine signals to modulate ingestive behavior. To further study a possible role of insulin in the control of food intake, male Wistar rats were subjected to various intra-third cerebro-ventricular applications of saline and insulin. Infusion of 2.0 mIU/rat of insulin at 1100 and 1900 decreased food intake in a 23.5 hr test period. Infusion of 0.5 mIU/rat of insulin between 1100 and 1200 decreased nighttime food intake during the 1st and 2nd days. Infusion of 2.0 mIU/rat/24 hr of insulin from osmotic minipumps decreased nighttime food intake throughout the active pump period and the effect persisted into the post-pump period. The results support the notion that insulin is involved in the regulation of food intake in the rat.