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Biomedical subjects

N Mrosovsky

Publications and source records attributed to N Mrosovsky.

At least 91 records · Page 5Linked to original sources
PubMed1989

Anorexic effects of interleukin 1 in the rat.

Interleukin 1 (IL-1) administration produces anorexia. Among unanswered questions about this effect are 1) whether it plays a role in the cachexia associated with chronic infection and cancer, and 2) whether IL-1 acts directly on food intake or indirectly by first lowering the set point for body weight. To investigate these questions, rats were infused with recombinant IL-1 continuously for 14 days through osmotic minipumps. Tolerance to the anorexic effects of the infusion developed within a few days. Control experiments showed that neither loss of IL-1 potency nor failure in the delivery system were responsible for recovery of food intake. Prior weight reduction completely overrode the anorexic effects of IL-1; previously food-restricted rats were hyperphagic initially despite receiving IL-1. This result is consistent with the view that IL-1 lowers the set point for body weight, but the development of tolerance prevented the full evaluation of this interpretation.

Animals↗
PubMed1989

Effects of induced wheel running on the circadian activity rhythms of Syrian hamsters: entrainment and phase response curve.

The goal of this study was to provide an example of nonsocial and nonphotic entrainment in Syrian hamsters, together with a corresponding phase response curve (PRC). Fourteen male hamsters were given 2-hr bouts of induced activity (mostly wheel running) at 23.83-hr intervals in constant darkness (DD). The activity onsets of 10 hamsters entrained to this manipulation, with no anticipatory activity present. After entrainment, the rhythms resumed free-running from a time 0.66-3.91 hr after the onset of the last bout of induced activity. Postentrainment free-running periods were shorter than pre-entrainment values. The PRC for 2-hr pulses of induced activity in DD revealed phase advances induced in some animals between circadian time (CT) 4 and CT 11 (approximately the last half of the hamsters' rest period), and delays between CT 23 and CT 3 and between CT 17 and CT 20. The CTs for phase advances are compatible with the phase angle differences observed between rhythm and zeitgeber at the end of entrainment. Many features of the results (not all animals entraining, PRC characteristics, lack of observable anticipation to the daily stimuli, phase relationship between zeitgeber and activity rhythms) are similar to those from a previous study on social entrainment in this species (Mrosovsky, 1988). These similarities reinforce the idea that induced activity and social zeitgebers act on activity rhythms via a common mechanism.

Animals↗
PubMed1989

Nonphotic enhancement of adjustment to new light-dark cycles: masking interpretation discounted.

The adjustment of hamsters to advanced light-dark (LD) cycles can be greatly accelerated by scheduling a single 3-hr bout of extra activity in a novel running wheel, starting about 7 hr before the time when the animals become active in the preceding LD cycle. The present experiments were designed to provide stronger evidence that this effect depends on a shift in the pacemaker rather than on masking. It was shown that when hamsters were put into continuous darkness (DD) 1 day after the exercise-accelerated phase shift, their free-running rhythms took off from a time nearer to the onset of darkness in the new LD cycle than in the preceding LD cycle. An incidental finding was that in DD the free-running period of the hamsters with the accelerated phase shifts was longer than that of the control animals. Further evidence that the 3-hr exercise pulse had produced a greater phase advance than that occurring in undisturbed control animals was obtained by giving a light pulse at the same clock time to all animals after they had been in DD for 8 days. The animals that had previously exercised for the additional 3-hr phase-advanced in response to the light pulse, while the undisturbed control animals phase-delayed.

Adaptation, Physiological↗
PubMed1988

Phase response curves for social entrainment.

Phase shifts in free-running activity rhythms of male golden hamsters, Mesocricetus auratus, often occur when they establish a new territory and home after a cage change. Similar shifts also often occur after pairs of animals interact with each other for half an hour. When these events take place during the middle of the hamsters' subjective day, they produce phase advances: when late in the subjective night, they produce phase delays. Repeated social interactions at the same time of day can entrain activity rhythms in a way consistent with the shape of the phase response curves. Not all individuals become entrained, as is predictable from the modest amplitude of the phase response curve. The effects of social interactions and of other disturbances may be mediated through an oscillator phased by general arousal. The present findings have implications for the interpretation of drug-induced changes in biological rhythms.

Animals↗
PubMed1987

Resistance to adipocyte hyperplasia in ground squirrels given high-fat diets.

Mammalian hibernators prepare for the winter by depositing fat in existing fat cells. There is little, if any, production of new fat cells. This is curious because equivalent fat deposition in rats is associated with substantial fat cell production. To determine whether degree of weight gain, diet composition, or some special mechanism militating against adipocyte hyperplasia may underlie the absence of adipocyte hyperplasia in hibernators, male Richardson's ground squirrels, Spermophilus richardsonii, were fed a fattening high-fat diet for either 5 mo or 1 yr. The 5-mo high-fat feeding period caused peak body weights to increase 36% relative to the peak body weights seen in control animals fed ordinary chow. Despite this increase, there was no apparent increment in fat cell number in any of the major fat depots. Animals fed the diet for 1 yr reached body weights similar to those of the 5-mo group but showed significant adipocyte hyperplasia in all fat depots studied. Thus adult ground squirrels are clearly capable of enlarging their pool of mature fat cells, but they fail to do so, at least at certain times, in response to conditions of weight gain that cause considerable adipocyte hyperplasia in rats.

Adipose Tissue↗
PubMed1987

Protection against fat cell hyperplasia in a hibernator, Glis glis.

Dormice, Glis glis, were fed a high-fat diet for 11 mo in one experiment: in another experiment they were fed a high-fat diet for 5 mo, either at room temperature (21.5 degrees C) or in a warm room (27 degrees C). Only in the latter group did adipocyte hyperplasia occur; this was significant in all the fat depots studied (inguinal, retroperitoneal, and gonadal). In the other groups there was no evidence of fat cell hyperplasia, despite weight gains from approximately 160 g (peaks on chow diet) to approximately 250 g (maximums on high-fat diet). Instead, fat cell size, assessed from biopsies of the inguinal area, became considerably enlarged. Taken together with earlier data from other species, the results suggest that hibernators are protected against fat cell hyperplasia. In dormice this protection appears to be present at all phases of their seasonal weight cycles. For species that experience several cycles of weight gain and loss in their lives, it may be adaptive to avoid increases in adipocyte number.

Adipose Tissue↗
PubMed1986

Lateral hypothalamic lesions in ground squirrels: rapid recovery and residual deficits.

The effects of lateral hypothalamic (LH) lesions were studied in golden-mantled ground squirrels, Spermophilus lateralis, a species of mammalian hibernator that displays endogenous circannual body weight cycles when kept in constant conditions. The lesions were made during the weight-gain phase. Evidence that the lesions were well placed included interruption of weight gain, transient aphagia, disrupted nest building, increased spillage of food crumbs and in some cases abnormal postures or movement. Despite these deficits most animals survived. Their body weights at the first postoperative peak of the cycle recovered either to within the control range (Experiment 1) or close to preoperative peak levels (Experiment 2). There was no evidence that the lesions lowered set points. The rapid recovery of weight and eating by ground squirrels given only dry rodent chow, after large lesions (1.5-2.5 mA, DC anodal, 15-25 s), contrasts with what is seen in rats following LH lesions.

Animals↗
PubMed1986

Colliding of activity onset and offset: evidence for multiple circadian oscillators.

When hamsters, Mesocricetus auratus, are kept in dim light, wheel running at the onset and the offset of their active phase have different circadian periods. As a result, the active phase expands and eventually the two activity components collide. There is then a temporary explosion of activity at a time that was previously in the rest period. This is followed by disorganization of the rhythm or by phase jumps. Such phase jumps probably stem from the interaction of two oscillators with different natural periods rather than from threshold changes for the expression of activity.

Animals↗
PubMed1986

Electrically induced behavior and neural specificity in ground squirrels and dormice.

Electrical stimulation of the lateral hypothalamus in 2 species of hibernator, dormice (Glis glis) and ground squirrels (Spermophilus lateralis), suggests that induced behaviors may reflect activation of specific neural systems, rather than merely activation of a single central mechanism interacting with internal and external cues and past experience (prepotency hypothesis). In dormice, the stimulation induced feeding on powdered food; in squirrels it induced either feeding or picking up of food pellets. Consistent with neural specificity in both species were high probabilities of emergence (78-81%) of a behavior during stimulation at an electrode site, with no greater ease of emergence at a second site tested. In squirrels, only 1 of the 2 behaviors emerged at a site, and there was independence between behaviors emerging at contralateral sites. Long-term reliability of the behavior initially observed at an electrode site was 100% despite infradian (dormice) or circannual (squirrels) cycles of body weight and food intake. Some squirrels consistently showed different induced behaviors at contralateral electrode sites throughout their circannual cycle. These observations suggest that feral species are valuable in investigations of mechanisms underlying electrically induced behaviors, and that reevaluation of the prepotency hypothesis may be in order.

Animals↗
PubMed1986

Body fat: what is regulated?

This paper assumes that body fat is regulated and then reviews our ignorance about how this is accomplished. It concentrates on the challenge posed by site differences between different depots, and discusses a variety of experimental approaches that may be helpful.

Adaptation, Physiological↗
PubMed1986

Meal patterns and food intakes of ground squirrels during circannual cycles.

Meal patterns in ground squirrels (Spermophilus lateralis) were recorded repeatedly over the course of endogenous circannual body weight cycles, with most data coming from the weight-gain phase. No manipulations were made, and the conditions were kept as constant as possible. Meal patterns were related to the level of food intake at each observation period. When the animals ate more, the most noticeable change was an elevated meal frequency. There were also some increases in meal size and the rate of ingestion. Postprandial correlations were generally positive, but rather variable and did not increase significantly when the animals ate more. On average 57% of the total intake occurred during the light phase of the LD 12:12 cycle. No systematic changes in the diurnality of feeding were detected. The meal patterns of hibernators when they are spontaneously hyperphagic show some resemblance to those seen in animals given exogenous insulin.

Animals↗
PubMed1986

Meal patterns of dormice.

Meal patterns were studied in dormice (Glis glis) kept at an ambient temperature of 25 degrees C. At this temperature there is no prolonged hibernation and the periodicity of cycles of food intake and body weight is about 2 months. The data on meal patterns were related to the level of food intake during repeated observation periods. The most pronounced changes were in meal frequency, but there were also significant increases in meal size when the animals ate more. Postprandial correlations were low and insignificant in most animals. Nevertheless, there was a significant strengthening of these correlations at times the animals ate more. Rate of ingestion remained stable. The dormice ate 70% of their food in the dark phase of the LD 12:12 cycle. Meal size in the night and day were similar and remained so when the animals ate more; meal frequency increased in both the night and the day at these times. There was no evidence that long-term seasonally-related changes in feeding in hibernators depend on the same neuroendocrine and metabolic mechanisms that are involved in circadian feeding cycles.

Animals↗
PubMed1985

Cycles of body fat in hibernators.

This paper reviews data on seasonal changes in body fat of mammalian hibernators. It then presents data on the fat cell number and size in the retroperitoneal and gonadal fat depots of dormice, Glis glis, over the course of their body weight cycles. Enlargement of fat cell size is the principal way that hibernators get fat. The hibernator cycle may provide a way of discovering whether regulation of fat level is achieved through regulation of total mass of fat or through regulation of the size of existing adipocytes.

Adipose Tissue↗
PubMed1983

Spontaneous obesity and weight loss: insulin action in the dormouse.

Dormice (Glis glis) undergo spontaneous cyclic changes in food intake and body weight. These infradian cycles with a periodicity of about 2 mo are endogenously controlled, since they persist in conditions of constant temperature and photoperiod. To evaluate the role of insulin as an effector of hyperphagia and fattening in dormice, experiments were conducted to study pancreatic function and adipose tissue metabolism during several phases of the infradian cycle. During the weight loss phase, peripheral insulin resistance occurs in the absence of hyperinsulinism. This resistance is not corrected by weight loss. Weight loss phase animals showed poor glucose tolerance and an impaired in vitro glucose-stimulated insulin secretion; these were not attributable to reduced pancreatic insulin content. Although basal glucose transport and basal, as well as insulin-stimulated, glucose utilization in isolated adipocytes were depressed during the weight loss phase, insulin-stimulated transport was significant. The data offer no evidence that insulin has a direct causal role in the development of spontaneous obesity in this species.

Adipose Tissue↗
PubMed1983

Spontaneous obesity and weight loss: insulin binding and lipogenesis in the dormouse.

Obese dormice (Glis glis) become anorexic during the weight loss phase of the 2-mo (infradian) body weight cycle. We have shown previously that this phase is characterized by severe insulin resistance, manifested by impaired insulin-stimulated glucose utilization in isolated adipocytes. Contrary to other obesity models, the insulin resistance was not accompanied by hyperinsulinism. In the present study, impaired lipogenesis was associated with decreased maximal insulin-binding capacity (due to a reduction in receptor concentration) and a postreceptor defect, which were exacerbated rather than attenuated during weight loss.

Adipose Tissue↗
PubMed1982

Sea-finding behaviour of loggerhead hatchlings: the time course of transient circling following unilateral and asynchronous bilateral blindfolding.

Marine turtle hatchlings orient seaward by responding to photic cues that guide them toward the brightest horizon. Earlier research has suggested that they have a positive phototropotactic reaction to light but the behaviour must be more complex than this because circling both toward the uncovered and the covered eye has been observed in unilaterally blindfolded turtles. The present work resolved some of these problems by studying circling direction as a function of how long one eye had been covered prior to testing. Different groups of neonate loggerhead turtles (Caretta caretta) were tested from 10 S to 19 h after the application of a unilateral blindfold. The longer this had been one, the less the turtle circled, but beyond 1 h further changes were slight. Initially, circling was predominantly toward the uncovered eye but after the blindfold had been on for 1 h circling toward the covered eye occurred equally often. The time course of circling was also examined in asynchronously, bilaterally blindfolded turtles. One eye was covered 6 h before the other, and tests were made at various times after the second eye had been covered. Asynchronous bilateral blindfolding caused more intense circling and disrupted seaward orientation more severely than unilateral blindfolding. The time course of the decline in circling showed similarities between both treatments, suggesting that they were activating the same mechanism. Dark adaptation was examined as a possible explanation of such transient turning tendencies and previous models of sea-finding were elaborated.

Animals↗