Abnormal Feeding Behavior Research Articles

Impaired glucose homeostasis and neonatal mortality in hepatocyte nuclear factor 3alpha-deficient mice.

Hepatocyte nuclear factors 3 (HNF-3) belong to an evolutionarily conserved family of transcription factors that are critical for diverse biological processes such as development, differentiation, and metabolism. To study the physiological role of HNF-3alpha, we generated mice that lack HNF-3alpha by homologous recombination in embryonic stem cells. Mice homozygous for a null mutation in the HNF-3alpha gene develop a complex phenotype that is characterized by abnormal feeding behavior, progressive starvation, persistent hypoglycemia, hypotriglyceridemia, wasting, and neonatal mortality between days 2 and 14. Hypoglycemia in HNF-3alpha-null mice leads to physiological counter-regulatory responses in glucocorticoid and growth hormone production and an inhibition of insulin secretion but fails to stimulate glucagon secretion. Glucagon-producing pancreatic alpha cells develop normally in HNF-3alpha-/- mice, but proglucagon mRNA levels are reduced 50%. Furthermore, the transcriptional levels of neuropeptide Y are also significantly reduced shortly after birth, implying a direct role of HNF-3alpha in the expression of these genes. In contrast, mRNA levels were increased in HNF-3 target genes phosphofructo-2-kinase/fructose-2,6-bisphophatase, insulin growth factor binding protein-1, and hexokinase I of HNF-3alpha-null mice. Mice lacking one or both HNF-3alpha alleles also show impaired insulin secretion and glucose intolerance after an intraperitoneal glucose challenge, indicating that pancreatic beta-cell function is also compromised. Our results indicate that HNF-3alpha plays a critical role in the regulation of glucose homeostasis and in pancreatic islet function.

Ecological and ecophysiological impacts of ferric dosing in reservoirs

The use of iron salts in the control of eutrophication of surface water reservoirs can only be successful if there are no environmental effects. We examined the acute and chronic effects upon Daphnia longispina, the dominant member of the zooplankton. Laboratory tests established that, although dissolved iron had no measurable effect, the presence of particulate iron caused mortalities in acute tests (48 hours) and reduced number of broods per female and numbers of young hatching in chronic tests (21 days). At 11.48 mg Fe l−1, 50% mortalities occurred in the population, whilst 4.49 mg Fe l−1 caused reductions in reproduction and increased mortality rates over 21 day tests. In inert china clay, similar results were observed, suggesting that it was the particulate nature of the ferric sulphate that caused the effects, rather than any toxic properties. A safe level of 1.69 mg Fe l−1 was calculated. The area of the filter of the third thoracic limb of the daphnids, from both the laboratory cultures and the south arm of Rutland Water (which received ferric-dosed inlet water) increased in size in the presence of ferric sulphate and china clay in chronic tests. This is a response to low food concentrations. Abnormal feeding behaviour was also observed in ferric sulphate. Thoracic beat rate, decreased in ferric sulphate but was unaffected in china clay. This suggested that the feeding rate depression was a response to the chemical nature of the ferric sulphate, rather than its particulate nature. The number of times that particles were rejected from the food groove increased in both ferric sulphate and china clay, in response to large clumps of these substances collecting there.

A Missense Mutation of the Gene for Na+,K+-ATPase α-Subunit Causes Abnormal Feeding Behavior inCaenorhabditis elegans

The Na+,K+-ATPase activity of membranes from a behavioral mutant ofC. eleganswas found to be about one-third that of the wild-type. The levels of mRNA and polypeptide of Na+,K+-ATPase α-subunit in the mutant were as high as those in the wild-type, but the level of the phosphorylated intermediate of the Na+,K+ATPase in the mutant worm was 80% lower than that in the wild-type. A single predicted amino acid replacement (Leu to Phe) was found in a highly conserved region in the α-subunit that is involved in the formation of phosphorylated intermediate. The abnormal feeding behavior of the mutant worm may be attributed to this missense mutation.

Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene.

Glucagon-like peptide 1 (GLP1) is postulated to regulate blood glucose and satiety, but the biological importance of GLP1 as an incretin and neuropeptide remains controversal. The regulation of nutrient-induced insulin secretion is dependent on the secretion of incretins, gut-derived peptides that potentiate insulin secretion from the pancreatic islets. To ascertain the relative physiological importance of GLP1 as a regulator of feeding behavior and insulin secretion, we have generated mice with a targeted disruption of the GLP1 receptor gene (GLP1R). These GLP1R-/- mice are viable, develop normally but exhibit increased levels of blood glucose following oral glucose challenge in association with diminished levels of circulating insulin. It is surprising that they also exhibit abnormal levels of blood glucose following intraperitoneal glucose challenge. Intracerebroventricular administration of GLP1 inhibited feeding in wild-type mice but not in GLP1R-/- mice; however, no evidence for abnormal body weight or feeding behavior was observed in GLP1R-/- mice. These observations demonstrate that GLP1 plays a central role in the regulation of glycemia; however, disruption of GLP1/GLP1R signaling in the central nervous system is not associated with perturbation of feeding behavior or obesity in vivo.

Neurotensin decreases with fasting in the ventromedian nucleus of obese Zucker rats

Neurotensin (NT) inhibits food intake when injected either in brain ventricles or in hypothalamic nuclei such as the ventromedian nucleus (VMN). NT concentrations are lower in obese than in lean Zucker rats in several hypothalamic nuclei, including the VMN. In this experiment, we studied the influence of the feeding state on NT concentrations in different brain areas of 10-week-old lean (n = 27) and obese (n = 27) Zucker rats that were fasted for 48 hours and then refed for 6 hours. NT level was measured in the microdissected areas by radioimmunoassay. Obese rats ingested approximately 50% more food than lean rats in the ad libitum (ad lib) condition ( P < .001) and 12% more during the refeeding time (NS). NT concentrations in the median eminence (ME) were 50% lower in obese than in lean rats ( P < .001). This decrease could be related to a 20% decrease in the arcuate nucleus (ARC) of the obese rats ( P < .04). NT concentrations in the ME and ARC, which are important for the control of pituitary hormone secretion by NT, were not changed by the feeding state in both genotypes. NT varied with the feeding state in the VMN only ( P < .04). Concentrations were 45% lower in fasted (FD) obese rats than in ad lib or refed (RF) obese rats (1.09 ± 0.25 ng/mg protein v 1.98 ± 0.36 ad lib and 1.62 ± 0.11 RF, P < .05). They remained unchanged in lean rats. NT variations in the VMN of obese rats could contribute synergistically with other neuropeptides to the abnormal feeding behavior of these rats.

Unexpected regulation of hypothalamic neuropeptide Y by food deprovation and refeeding in the Zucker rat.

Neuropeptide Y strongly stimulates food intake when it is injected in the hypothalamic paraventricular (PVN) and ventromedian (VMN) nuclei. In Sprague-Dawley (SD) rats, NPY synthesis in the arcuate nucleus (ARC) is increased by food deprivation and is normalized by refeeding. We have previously shown that the obese hyperphagic Zucker rat is characterized by higher NPY concentrations in this nucleus. NPY might therefore play an important role in the development of hyperphagia. The aim of the present study was to determine if the regulation by the feeding state works in the obese Zucker rat. For this purpose, 10 weeks-old male lean (n=30) and obese (n=30) Zucker rats were either fed ad libitum, either food-deprived (FD) for 48 hours or food-deprived for 48 h and refed (RF) for 6 hours. NPY was measured in several microdissected brain areas involved in the regulation of feeding behavior. NPY concentrations in the ARC was about 50 % greater in obese rats than in lean rats (p < 0.02) whatever feeding state. In the VMN, NPY concentrations were higher in the lean FD rats than in the obese FD rat (p < 0.001). Food deprivation or refeeding did not modify NPY in the ARC, in the VMN or in the dorsomedian nucleus whatever the genotype considered. On the other hand, food deprivation induced a significant decrease in NPY concentrations in the PVN of lean rats. This decrease was localized in the parvocellular part of this nucleus (43.0 ±1.9(FD) vs 54.2 ± 2.1 (Ad lig) ng/mg protein ; p < 0.005). Ad lib levels were restored by 6 hours of refeeding. These variations were not observed in the obese rat. The regulation of NPY by the feeding state in the Zucker rat was therefore very different from that described in the SD rats. Strain or age of the animals used might explain these differences. High NPY levels and absence of regulation in obese Zucker rats could contribute to the abnormal feeding behavior of these rats.

Abnormal feeding behavior and insulin replacement in STZ-induced diabetic rats

The present studies were undertaken to investigate whether or not decreased ambulatory activity, including abnormal feeding behavior in diabetic rats, will be simultaneously normalized by insulin administration. To do this, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. In this study, 3 U NPH insulin were administered at 1800, just before the dark phase, and 2 U were administered at 0600, just before the light phase. With these insulin doses, we found that 5 weeks were needed to normalize ambulatory activity, 4 weeks were necessary for food intake, 6 weeks for drinking and 2 weeks for body weight. Since ambulatory activity is reported to be related to changes in dopamine turnover, further studies are in progress to determine whether or not dopamine turnover is normalized when there is no difference in ambulatory activity due to insulin replacement.

MK801 prevents quinolinic acid-induced behavioral deficits and neurotoxicity in the striatum

Bilateral intrastriatal injections of quinolinic acid (QA) (180 nmoles) induced weight loss and neurologic and behavioral deficits including convulsions, decreased catalepsy response to haloperidol, increased nocturnal locomotor activity, and abnormal feeding behavior in adult male Sprague-Dawley rats. Pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK801 (4 mg/kg IP) 30 min prior to stereotaxic surgery prevented the appearance of all QA-induced behavioral abnormalities and prevented weight loss. Twelve weeks after surgery the QA-lesioned animals recovered to sham levels on feeding behavior and nocturnal locomotor activity, but showed persistent reductions in haloperidol-induced catalepsy. Histological examination of the QA-lesioned brains showed extensive lesions of the dorsolateral striatum and frontoparietal cortex. MK801 pretreatment protected against these lesions. These results confirm that MK801 treatment prevents the appearance of neuropathological damage after QA neurotoxicity, and further show that neuronal protection with MK801 is correlated with the absence of QA-induced behavioral deficits.

Studies on Abnormal Feeding Behavior in the STZ-induced Diabetic Rat

Studies on Abnormal Feeding Behavior in the STZ-induced Diabetic Rat

The effects of acidic sea water on young carpet-shell clams Venerupis decussata (L.) (Mollusca: Veneracea)

Young carpet-shell clams Venerupis decussata (L.) were maintained in sea water over a pH range of 3.5 to 8.2 (control), for periods from 8 to 30 days. Shell dissolution occurred at pH ⩽ 7.55. At pH < 7.0 feeding was inhibited, and both tissue and shell growth were significantly reduced. There were ⩾ 50% mortalities over the time scale of the experiment at pH ⩽ 6.5, with smaller (3–4 mm) clams more sensitive than larger (7–9 mm) clams. The animals showed reduced activity at pH<6.0, with abnormal feeding behaviour, exhibited by hyper-extension of the siphons; greater time spent with the valves closed at these pH levels may have marginally reduced the deleterious effects. It is concluded that pH levels below those found naturally in the sea are intolerable to young V. decussata.

Abnormal feeding behavior of western toads ( Bufo boreas) kept in a hyperosmotic environment. I. A quantitative behavioral analysis as related to cerebral amino acid concentrations

Discriminant analysis of eleven behavioral variables associated with feeding permitted the assignment of hyperosmotically-acclimating (HOA) toads ( Bufo boreas) to six different behavioral states. These behavioral states could be correlated with specific alterations in the level of select amino acids in three regions of the toad's central nervous system. By considering only those amino acids that showed equivalent levels in corresponding brain regions of normally-behaving, freshwater-acclimating (FWA) and HOA toads, it was possible to focus upon just nine amino acids as possible modulators of feeding behavior. Four of these amino acids were markedly elevated in two or more abnormal behavioral states: gamma-aminobutyric acid (GABA) in all three brain areas; glutamate in the cerebral hemispheres; aspartate in the cerebral hemispheres and olfactory bulbs; and phenylalanine in the olfactory bulbs and optic lobes. Other possible behavior modulators identified were: lysine and threonine in the cerebral hemispheres; carnosine in the olfactory bulbs; and valine and alanine in the optic lobes.

The action of the anterior feeding apparatus of Caenorhabditis elegans (Nematoda: Rhabditida)

From analysis of ciné film, combined with ultrastructural observations, the anterior feeding structures and their behaviour in the free‐living microbivorous nematode Caenorhabditis elegans during ingestion in dense and sparse suspensions of Escherichia coli are described In dense suspensions bacteria accumulate in the buccal cavity against the three metastomal flaps that nearly close it, and are then swallowed down the three tubular apical expansions of the triradiate oesophageal lumen when the flaps open. Excess medium is then expelled, as the oesophageal lumen closes and traps the swallowed bacteria. The flaps and oesophagus operate by contractions in the seven most anterior oesophageal muscle cells, probably coordinated via proprioceptive nerve endings between the cells. About one million nematode hours are needed to extract 1 g of bacteria from 30 ml of medium. With few or no bacteria, the head moves more, the metastomal flaps do not close and medium seems to pass in and out of the buccal cavity, probably as part of the widespread exploration phase of food‐finding behaviour. Abnormal feeding behaviour, control and functions of the metastomal flaps and associated structures, and control of food intake volume are discussed.

Abnormal heart rate response during newborn sucking behavior study: Subsequent sudden infant death syndrome with cardiac conduction abnormality

This report concerns a four-month-old white female infant who exhibited abnormal feeding behavior and EKG irregularities during a newborn sucking behavior study. The immediate post-birth history showed an irregular heart rate on two occasions, but a cardiac consultation elicited no unusual findings. During sucrose sucking conditions, the heart rate increased with a beat-to-beat variation of 50 beats per minute, noted to be due to premature atrial beats. At 39 days, an EKG showed a marked sinus tachycardia of 156, a PR interval of 0.08, QRS of 0.05 and a QT of 0.26. The infant was diagnosed as a sudden infant death syndrome (SIDS) following an unexpected death at home. Subsequent cardiac pathology revealed an anomalous tract between the right atrium and the atrioventricular (AV) bundle which formed an extensive bypass of the AV node (atrio-His tract), and two accessory AV connections between the left atrium and posterior left ventricle. These findings are consistent with the Wolff-Parkinson-White syndrome type A. Only further studies can determine whether such abnormal feeding behavior with EKG irregularities can be used to identify infants who are at high risk for sudden death.