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Effects of high dietary cholesterol on erythrocyte membrane lipids were studied. Feeding rats with a diet containing 0.5% cholesterol and 0.15% sodium cholate for two weeks induced changes in erythrocyte membrane lipids including a decrease in cholesterol, an increase in alpha-tocopherol (alpha-Toc) and changes in the fatty acid composition of phospholipids. Oleic acid and linoleic acid increased, while arachidonic acid decreased in phosphatidylcholine. Saturated fatty acids decreased and unsaturated fatty acids increased in phosphatidylethanolamine. Almost the same changes in membrane lipids were also noted after six weeks of feeding rats with the diet. A diet containing 0.5% cholesterol but without sodium cholate caused a decrease in erythrocyte cholesterol and an increase in erythrocyte alpha-Toc after two weeks of feeding, as compared to the basal diet, indicating that high dietary cholesterol, but not sodium cholate, was responsible for these changes in the erythrocyte membrane.

The anti-tumor effect of a dietary supplement obtained from mixed cultures of several lactic acid bacteria was examined in the colon of tumor-inducing ICR male mice by use of a carcinogen, 1,2-dimethylhydrazine (DMH, 20 mg/kg body weight, 1 intra-muscular injection per week for 10 weeks). The animals were sacrificed either 15 weeks or 24-26 weeks after the first carcinogen injection. Macroscopically, the incidence of colon tumors at a 24-26 week period of tumor induction was apparently lower in mice treated with both the DMH and dietary supplement (76%) than in those treated with DMH alone (100%). Histologically, microadenomas were induced predominantly in the anal half of the total colon, and large lymphoid aggregates were often associated with dysplastic crypts in the distal colon. Apoptotic cell masses were shed into the distended lumen of the involved crypts. The statistical analysis at a 15-week period of tumor induction indicated that the incidence of microadenomas per tumor-induced mouse was lowered significantly by use of the dietary supplement. From the present results, it is suggested that the intake of the dietary supplement inhibits the early development of colon adenomas, and the inhibition of microadenomas results in a reduction of subsequent polyp and tumor yield in the mouse colon.

A new economical and compact device for measuring dry food intake in rats is described. The apparatus consists of a spill-proof feeding box with a slotted space on a front panel, through which a rat is allowed to feed, and a feeding cup fixed inside the box. The apparatus with five different kinds of openings—i.e., vertical slots, in each 2.5, 4.0 or 6.0 cm wide, a horizontal slot of 4.0 cm in width and an open space without a slot—were evaluated for an accurate measurement of undisturbed food intake. Out of these, the feeding box with a vertical slot of 4.0 cm in width, approximately 0.5–1.0 cm wider on each lateral side than the maximal transverse cranial diameter of rats, was found to be most practical; natural growth function of the body weight was not disturbed and dry food was neither scattered nor mixed up with urine and feces. The device should prove particularly useful in the measurement of dry food intake in small animals.

In order to clarify subtle metabolic changes and the time course of metabolic variations associated with the central mechanisms of feeding and satiety, serum obtained from fasted rats during various hunger stages was profiled using a gas chromatography-mass spectrometry-computer system. On the basis of this work, chronobiological changes in metabolites following fasting were also evaluated. It was found that sampling method was critically important for determining the levels of organic acids. Changes in the time course of these organic acids were mainly divided into two patterns: a progressive increase over long-term starvation and a transient increase at about 36 hr of starvation. The levels of free fatty acids, 3-hydroxybutyrate, 2-deoxytetronate and 3-deoxypentonate were elevated around twilight after 24 and 36 hr of fasting. It was concluded that these organic acids were probably the compounds which elicit feeding behavior.

Formation of gastric lesions, changes in body weight and changes in serum level of endogenous chemical substances in response to stressful stimuli were studied. To examine the influences of stressful events on bodily responses, the stimuli were introduced in the terms of affective communication by using a communication box. The “Sender” received physical stimuli of electric foot shocks and the “Responder” received affective information such as visual, auditory, and olfactory cues from “Sender” with no exposure to foot shock. The “Responder” exhibited significantly more severe gastric lesions than the “Sender.” The degree of susceptibility to the formation of gastric lesions and weight reduction increased when the stimuli were administered during the dark cycle. Changes in the level of endogenous chemical substances were not significant. The results indicated that a circadian rhythm can be detected in susceptibility to gastric lesions in response to indirect stimulus cues.

1,5-Anhydroglucitol (1DG, minus an oxygen on carbon 1 of the glucose molecule), has been known physiologically to be present in human cerebrospinal fluid. In order to clarify direct evidence concerning 1DG-induced feeding, hyperglycemia and adrenomedullary mediation of hyperglycemia, 1DG was infused into rat lateral ventricle in doses of 11.8, 21.0, 33.7 and 50.0 μmoles/rat, and its effects compared to those of 2-deoxy-D-glucose (2DG). A dose-dependent increase in food intake after 1DG was 1/3.4 to 1/10.6 of that produced by equimolar 2DG. After 1DG serum glucose concentration gradually increased, peaked at 30 min, and subsequently decreased. Hyperglycemia induced by 1DG was 1/2.1 to 1/2.2 of that produced by 2 DG and was reduced 81% following adrenomedullectomy, which was close to the value for 2DG: 80%. Results were consistent with known differences in the biochemical actions of 1DG and 2DG at the level of substrate specificity of the hexokinase and the rate of glucose transport. These actions suggest that 1DG could provide physiological signals for food intake.

1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at -120, -60 or -15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.

Under natural circumstances,twilight is known to play an important role in behavioral and metabolic changes in mammals. Since experimental rooms are usually illuminated by on-off lighting system, an artificial twilight system was devised and its effect on feeding, drinking and motor activity was compared with those in on-off system. Following 10 days of on-off lighting (a 12:12 light-dark cycle), a twilight regimen was introduced. Illuminant intensity increased from 0 to 90 lumen during a 2 hr period of dawn and decreased reversely during same hour period of dusk. Three different types of twilight conditions were tested, i.e., (1) dawn: 0800-1000 hr and dusk: 1800-2000 hr, (2) dawn: 0600-0800 hr and dusk: 2000-2200 hr, (3) dawn: 0600-0800 hr and dusk: 1800-2000 hr. Total amount of 24-hr consumptions or activity was not influenced following the twilight conditions. Immediately after a period of dawn started, rats decreased food and water intake subsequent to their increase during the later periods of dark. During a dusk period, food and water intake increased markedly during twilight conditions in type 3. In type 1, however, such facilitated effects were not found.