Further evidence for the existence of an "organismic" set point in rats with dorsomedial hypothalamic nucleus lesions (DMNL rats): normal catch-up growth

The present study was performed to assess the capacity of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) and sham-operated controls (CON) for catch-up growth following body weight (b.wt.) reduction prior to DMNL (and sham-lesion) production. Male SD rats (45 days, 157 +/- 1.3 g) were maintained for 11 days ad lib (ADLIB) after arrival and then divided into two groups. One group continued to feed ADLIB, the other group was fed half of the ration eaten by ADLIB rats for 32 days. At this point each group was divided into two subgroups. One subgroup received DMNL, the other subgroup consisted of CON. From then on all rats were fed ADLIB [except for one group of CON that was pair-fed to the ADLIB DMNL rats (PF-CON)] for 37 days (69th day of experiment) and then killed. DMNL rats lesioned at normal b.wt. (ADLIB DMNL) showed a precipitous drop in food intake, b.wt. and efficiency of food utilization (EFU). In striking contrast, rats that had received DMNL after b.wt. restriction (REST DMNL) and were then refed ADLIB showed a dramatic rise in food intake, b.wt., change in b.wt. and EFU, the latter being almost twice that of the ADLIB DMNL. Notably, the PF-CON weighed less than the ADLIB CON and utilized food poorer than ADLIB CON, REST CON and ADLIB DMNL. Liver weight (both absolute and relative (per kg 3/4 b.wt.) was reduced in DMNL irrespective of dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feed efficiency in growth-retarded rats with ventromedial and dorsomedial hypothalamic lesions produced shortly after weaning

Weanling male rats received electrolytic lesions (L) in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei; sham-operated rats served as controls. The animals were maintained for various periods up to 50 postoperative days on lab chow under standard conditions. In a short-term study, food intake and body weights were measured daily and body weight gain was divided by the food eaten to obtain the efficiency of food utilization. Also, gains in metabolic size ($\text{kg}\text{3}\text{4}$) were divided by food eaten. Both manipulations showed that DMNL rats, except for the first two postoperative days, utilized food normally. The same changes were obtained for weanling VMNL rats, except that they did not show a decline in utilization during the first two postoperative days. Computation of efficiency of food utilization for both VMNL and DMNL rats over postoperative durations ranging from 7 to 50 days showed that among 12 out of 14 experiments DMNL rats utilized food as well as controls. Out of 8 experiments, rats with VMNL utilized food better for weight gained than controls in one and poorer than controls also in one experiment; in reference to metabolic size they utilized food normally. The foregoing data, gathered from 225 DMNL, 64 VMNL and 181 control rats show quite convincingly that food utilization in both types of experimental animals is unimpaired despite profound reductions in ponderal and linear growth and food intake in the DMNL rat and reduced circulating growth hormone levels in the VMNL rat.     

Meal patterns of rats with dorsomedial hypothalamic nuclei lesions or sham operations

Rats with bilateral dorsomedial hypothalamic electrolytic lesions (DMNL rats) are hypophagic, hypodipsic and have reduced linear and ponderal growth when compared to sham operated controls (SCON). Nevertheless, previous studies have shown that DMNL rats eat and drink adequate amounts for their size and have normal body composition. In the present study we investigated meal parameters: meal size, and frequency (both light and dark period), total intake and meal size per metabolic size (body weight 0.75). Compared to SCON, DMNL rats at twelve days post surgery weighed less, were shorter, but had a normal body composition as determined by the Lee Index, and were hypophagic (grams eaten/day). The animals were placed into individual, self-contained feeding modules and given powdered chow. After familiarization to the modules, meal parameters were recorded continuously by a computer for an eight day period. While dark phase meal frequency did not differ significantly between groups, the lesioned rats took more meals during the light period. Over the eight-day measurement period DMNL rats were hypophagic compared to SCON in absolute terms. However, when total intake and meal size were normalized to metabolic size, these two parameters did not differ significantly between groups. Upon refeeding, after a one-day fast, the initial meal size of the normally hypophagic DMNL rats exceeded that of SCON. Rats with DMNL have previously been shown to have deficits in some hypothesized short-term food intake control mechanism (e.g., cholecystokinin, glucose sensing). Thus overeating by the lesioned rats after a fast could possibly result from a specific short term control deficit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatic and metabolic responses of mature female rats with dietary obesity to dorsomedial hypothalamic lesions: Effects of diet palatability

Caloric intake, body weight, obesity status (Lee Index) and incorporation of U-14 C-glucose into liver and retroperitoneal fat pad glycogen and lipid were studied in mature female rats that had received bilateral lesions or sham-operations in the dorsomedial hypothalamic nuclei (DMN) after dietary obesity was well established. Their diet consisted of a high-fat-sucrose chow mix, chocolate chip cookies and a drinking fluid of 32% sucrose in tap water. Comparable groups of DMN lesioned rats (DMNL rats) and sham-operated controls were maintained on lab chow pellets and tap water. Prior to the hypothalamic operation, the animals on the high-caloric regimen consumed significantly more calories than the rats on lab chow and also attained commensurately higher body weights and obesity indices. The bulk of the calories consumed during this time was derived from the cookies. Following DMNL, the animals maintained on lab chow became hypophagic and had lower body weights than the sham-operated rats, as has been previously reported. In rats on the high-caloric regimen, DMNL resulted in hyperphagia in comparison to all other groups. The greatest percentage of the calories during this time was derived from the high-fat-sucrose chow mix and sugar water. Correspondingly, DMNL rats on the high-caloric regimen had higher body weights and obesity indices than all other groups. At sacrifice, both a diet and lesion effect were noted in an elevated incorporation of U 14-C glucose in both fat pad and liver lipid and glycogen. The data are interpreted to mean that (1) when a highly palatable, high-caloric diet is available, DMNL do not exert their usual hypophagic and weight-lowering effects; (2) DMNL and control rats show excessive caloric intake when both groups are fed a highly palatable, high-caloric diet in comparison to their chow-fed counterparts. However, DMNL rats fed high-caloric diet also consume significantly more than controls fed this diet; (3) This excessive caloric intake of the DMNL rats possibly predisposes these animals to exaggerated lipogenesis in liver and adipose tissue; (4) the sham-operated controls on the high-caloric regimen also show greater lipogenesis but at a level intermediate between the chow-fed controls and the DMNL rats on the high-caloric diet.     

Naloxone suppression of food and water intake and cholecystokinin reduction of feeding is attenuated in weanling rats with dorsomedial hypothalamic lesions

In Experiment 1, sham operated (SCON) and dorsomedial hypothalamic nuclei (DMN) lesioned (L) rats were given saline or naloxone (0.1, 1.0 or 2.0 mg/kg) just prior to the onset of the dark cycle, lights out. Compared to saline injections, naloxone at all doses suppressed the cumulative food intake of the SCON during the second and third hr of measurement. Naloxone was without significant effect on the food intake of DMNL rats. Similar results were obtained in Experiment 2, except that naloxone at 2.0 mg/kg significantly suppressed the DMNL rats' food intake by the fourth hr of measurement. Cumulative water intake of both groups was significantly suppressed by naloxone in both experiments but its effects appeared to be attenuated in the DMNL group. In a preliminary trial cholecystokinin octapeptide (3.0 and 6.0 micrograms/kg) given at the onset of the dark cycle significantly suppressed the food intake of the SCON group but had no significant effect on the DMNL rats. The possibility exists that the reduced food intake and lower body weight of DMNL rats may partially result from damage to an opioid system. The data also tentatively suggest that DMN may play a role in cholecystokinin-induced satiety.     

Paraventricular nucleus lesions in weanling female rats result in normophagia, normal body weight and composition, linear growth and normal levels of several plasma substrates

Female weanling rats received small (1 mAmp for 5 sec) electrolytic lesions in the paraventricular nuclei. Sham-operated rats served as controls. The rats were maintained for 42 days and body weight, linear growth, Lee Index, food intake and efficiency of food utilization were determined throughout the study. Plasma glucose, glycerol, free fatty acids, total protein and carcass fat and protein were determined at sacrifice. There was no significant difference between the lesioned and the sham-operated rats in any of the parameters measured. The findings are interpreted to mean that the PVN of the weanling rat is not functionally mature or alternatively, that there exists a sex difference in weanling rats in response to PVN lesions.     

Failure to demonstrate disruption of ultradian growth hormone rhythm and insulin secretion by dorsomedial hypothalamic nucleus lesions that cause reduced body weight,linear growth and food intake

Summary Weanling male rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated animals served as controls. At the end of a 39-day postoperative period DMNL rats were lighter and shorter than controls and also exhibited significant hyopophagia. Their efficiency of food utilization (weight gained for the amount of food eaten) was normal, however. Subsequent determination of plasma growth hormone (GH) and insulin (IRI) levels every 15 min for 6-h periods from freely moving chronically cannulated rats showed no differences in pulsatile patterns and peaks of GH nor in plasma IRI levels between DMNL rats and controls. There was also no significant difference between mean 6-H GH and IRI concentrations between the two groups. The reduced body weight, length and food intake are apparently unrelated to the normal GH and IRI secretory patterns. In conjunction with previous data indicating normal somatomedin activity and normal responses to various homeostatic challenges, the data make a strong case for the argument that DMNL rats are not growth-retarded. Rather, they are normal animals that are scaled-down to a smaller size with maintenance of normal homeostatic capacity. This has been hypothesized to be due to the existence in these animals of an organismic set point.     

Effects of guanethidine sympathectomy on feeding, drinking, weight gain and amphetamine anorexia in the rat

Adult female rats that underwent sympathectomy induced by guanethidine treatment (10, 20 or 40 mg/kg) exhibited markedly increased water intake, but did not display significant alterations of either food intake, body weight, or the Lee Index of obesity. Guanethidine treatment did not attenuate amphetamine anorexia as evidenced by comparable dose-dependent reductions in food intake to d-amphetamine sulfate (0.25, 0.50, 1.0, and 2.0 mg/kg) in sympathectomized and control rats. These data are not consistent with the hypothesis that amphetamine anorexia is partially mediated via enhanced BAT thermogenesis.     

Dorsomedial hypothalamic lesions at weaning and ovariectomy after maturity: Somatic and metabolic changes

Weanling Sprague-Dawley rats received lesions in the dorsomedial hypothalamic nuclei or sham operations. Analysis of variance revealed a significant lesion-induced depression of body weight (BW) and food intake (FI). After sexual maturity, bilateral ovariectomy (OVX) and/or sham-ovariectomy (S-OVX) were performed in each of the above groups. OVX produced a significant increase in BW in both lesioned and non-lesioned rats without changes in food intake. Following DMN lesions efficiency of food utilization (EFU) was greater than normal and OVX caused a further significant increase, irrespective of hypothalamic manipulation. DMN lesions, as previously shown, were followed by a reduction in linear growth; subsequent OVX exerted a growth-promoting effect in both DMN-lesioned and sham-lesioned rats. However, OVX did not alter plasma growth hormone or insulin levels. When calculated on the basis of per gram tissue protein, DMN lesions significantly diminshed the incorporation of glucose into lipids of diaphragm and fat pad, but not of liver. DMN lesions had no effect on the incorporation of glucose into glycogen of diaphragm, fat pad or liver. OVX did not produce significant changes in lipogenesis from glucose or incorporation of glucose into glycogen in either sham-lesioned OVX or DMN-lesioned OVX rats. The data support the concept that increased weight gain following OVX can be attributed to factors other than increased food intake. They also support previous findings that DMN lesions lower the BW “settling point” (i.e., both lean body mass and fat commensurately). The data also suggest that the DMNL rat is responsive to various manipulations—in this case OVX—of the adipose tissue mass “settling point”.     

Somatic, endocrine and metabolic changes in controls pair-fed for six weeks to rats with dorsomedial hypothalamic nucleus lesions (DMNL rats)

One group of weanling male Sprague-Dawley rats received lesions in the dorsomedial hypothalamic nuclei (DMNL rats), whereas two additional groups of rats were sham-operated (CON). One of these CON groups was allowed to feed ad lib (CON-ADLIB) while the other CON group was pair-fed for 6 weeks to the DMNL rats (CON-PF). Despite eating the same amount of food as DMNL rats. CON-PF animals had consistently lower body weights and also utilized food energy more poorly than DMNL rats. The CON-PF group also had smaller kidneys and less percent liver protein but more epididymal fat pad percent protein than DMNL rats. Whereas plasma glucose concentrations were comparable among the three groups, insulin levels were significantly higher, and free fatty acid levels lower in CON-PF than in DMNL rats. The CON-PF group incorporated less glucose-U-C14 carbon into liver glycogen but more of the tracer into liver lipid than the DMNL group. Glucose carbon was also incorporated more avidly into epididymal fat pad lipid by CON-PF than by DMNL rats. The data not only confirm previous findings in DMNL rats but in addition show that the neurologically intact rats fed the same amount of food that is eaten spontaneously by DMNL rats show somatic and metabolic alterations that suggest that they cannot cope with this low amount of substrate. The normalcy of the DMNL rats, compared to ad lib-fed sham-operated controls, in all metabolic parameters suggests that the low food intake is indeed "normal" for this preparation and may be the reflection of an "organismic" set point.     

Risperidone alters food intake, core body temperature, and locomotor activity in mice

Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p = 0.050) and gained more weight (p = 0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p = 0.046), but not body temperature (p = 0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p = 0.0001), and tended to be higher during the dark phase (p = 0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p = 0.006); there were no differences in activity during the light phase (p = 0.47). UCP1 (p < 0.01) and UCP3 (p < 0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p < 0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.     

The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies

This review article discusses the well-established role of the dorsomedial hypothalamic nucleus (DMN) in feeding, drinking and body weight (BW) regulation. DMN lesions (L) in both weanling and mature rats of both sexes produce hypophagia, hypodipsia and reduced ponderal and linear growth in the presence of normal body composition. The growth reduction is not due to a deficient secretion of growth hormone, insulin-like growth factor-1, thyroxine, triiodothyronine or insulin. DMNL rats actively defend their lower BW (BW settling point) by becoming either hyper- or hypophagic, depending on the experimental manipulation, thereby defending both lean and fat mass. They also regulate their 24-h caloric intake, but they may overeat during the first hour of refeeding following a fast, possibly due to a reduced ability to monitor blood glucose or to respond to cholecystokinin (CCK). 2-Deoxy-D-glucose (2DG) increases c-fos expression in orexin-A neurons in the DMN, and DMNL eliminated the orexigenic effect of 2DG. DMNL rats on high-fat diets do not get as obese as controls, which may be due to a reduction of DMN neuropeptide Y (NPY). Rats lacking DMN CCK-A receptors are obese and have increased expression of NPY in the DMN, supporting earlier data that CCK may act at the DMN to suppress food intake. Excitotoxin studies showed that loss of DMN cell somata, and not fibers of passage, is important in the development of the DMNL syndrome. The DMN is a site where opioids increase food intake and knife-cut studies have shown that fibers traveling to/from the DMN are important in this response. An interaction of glucose and opioids in DMN may also be involved in the control of food intake. DMN knife cuts interrupting fibers in the posterior and ventral directions additively produce the hypophagia and reduced linear and ponderal growth observed after DMNL. Ventral cuts may interrupt important connections with the arcuate nucleus. Lateral and posterior DMN cuts additively produce the hypodipsic effect seen after DMNL, but DMNL rats respond normally to all water-regulatory challenges, i.e., the hypophagia is not due to a primary hypodipsia. The DMN has been shown to be involved in the rat's feeding response to an imbalanced amino acid diet. These data show the DMN has an important role in many processes that control both food intake and BW regulation.     

Failure to demonstrate early metabolic changes in weanling growth-retarded hypophagic rats with lesions in the dorsomedial hypothalamic nuclei

Experiment 1: Weanling male rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated animals served as controls. Rats were killed four hours and three and seven days postoperatively (post-op). Plasma was obtained and epididymal fat pads, diaphragm and liver aliquots were harvested and the in vitro incorporation of U-14C-glucose into CO2, glycogen, lipid and saponifiable fatty acids (FAs) were measured. Body weight, carcass lipid and food intake were significantly lower in DMNL rats than in controls. The only significant lesion-induced metabolic changes were hypoglycemia and greater tracer incorporation into epididymal fat pad lipid and diaphragm glycogen. Both DMNL rats and controls showed similar time courses of tracer incorporation into epididymal CO2 and FAs, diaphragm lipid and liver CO2, glycogen, lipid and FAs. Lesioned rats also showed more pronounced decreases of tracer incorporation from day 0 to day 3 in epididymal glycogen and lipid and diaphragm CO2 and glycogen. These data make it appear unlikely that very early deficits in glucose metabolism are the cause of the growth retardation seen in long-term studies with DMNL rats. The data also demonstrate considerable locus specificity, since weanling rats with ventromedial hypothalamic lesions (VMNL rats) in similar short-term studies have shown dramatic alterations in the above parameters. Experiment 2: Weanling DMNL rats and sham-operated rats were injected via tail vein with tritiated water one hour post-op. One hour after the injection they were decapitated. There were no significant differences between DMNL rats and controls in mumoles tritiated water incorporated into total liver, grams liver tissue, mg liver glycogen and ml or mg plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developmental aspects of sucrose-induced obesity in rats

Daily caloric intakes and body weights were measured from weaning to 70 days of age in male Sprague-Dawley rats given access to either a standard laboratory diet and water, or the standard diet, a 32% sucrose solution and water. Lee index of obesity (3 square root body weight/naso-anal length) and fasting blood glucose levels were determined at 46, 57, and 70 days of age. Animals were sacrificed at 70 days, and body composition analyses were performed. Aniamls given access to the sucrose solution consumed significantly more calories per day than animals given only the standard diet. Sucrose animals took approximately 50 to 60% of their daily caloric intake from the sugar solution. Despite the greater caloric intakes of the sucrose animals, sucrose and control animals did not differ in body weight. While there were no differences in body weights between the two groups, the Lee Index of obesity was significantly greater in the sucrose animals than in controls as early as 46 days of age. Fasting blood glucose levels were significantly lower in sucrose animals than in controls at both 46 and 57 days of age. Direct determinations of body compositions when animals were 70 days of age revealed that animals with access to sucrose had significantly greater percentages of body fat and lower percentages of body protein than controls.     

The weanling rat ventromedial syndrome: males get just as fat as females

Weanling female and male Holtzman rats received bilateral electroytic lesions in the ventromedial hypothalamic nucleus (VMN) at the age of 27 and 26 days, respectively. Sham-operated rats served as controls. The animals were maintained on a synthetic diet (4.2 Cal/g) and tap water ad lib, and body weight, Lee (obesity) Index, tail length and food and water intake were recorded weekly for 6 weeks. The only parameters in which a significant sex difference could be demonstrated were body weight gains and water intake which were greater in the male VMN rats. Female and male VMN rats also utilized food energy for fat deposition, body weight and body length change to the same extent. The data also show that in growing animals, body weight is a poor criterion for the accurate assessment of obesity status and true growth.     

Effect of chronic insulin administration on food intake and body weight in rats.

Insulin was chronically administered to rats to determine its effect on the daily changes in food intake and body weight. Animals received regular insulin via 14-day osmotic minipumps in doses of 0.0, 0.5, 1.0, 3.0, and 5.0 IU/day treated either with (+GLU) or without glutamic acid (-GLU). Previous studies have shown that glutamic acid prevents insulin aggregation in the minipumps to provide a more stable flow rate. Food intake and body weights were measured each day of treatment. Chronic insulin treatment was ineffective in promoting changes in animals receiving any dose of insulin except the highest dose. Animals receiving 5.0 IU/day insulin + GLU experienced a transient hyperphagia and weight gain followed by a suppression in food intake and body weight by Day 4 of treatment. Effects were attenuated in animals receiving insulin -GLU. Plasma insulin concentrations on Day 14 were similar for all doses, suggesting a compensation took place either in insulin degradation or endogenous insulin production. Results indicate that glutamic acid treatment enhances the effects of chronic insulin administration via osmotic minipumps.     

Effect of diet consistency, taste and calories on food intake of weanling rats with dorsomedial hypothalamic lesions

Male weanling Sprague-Dawley rats with dorsomedial hypothalamic lesions (DMNL rats) primarily destroying the dorosomedial hypothalamic nuclei (DMN) showed significant hypophagia on lab chow chunks compared to sham-operated controls. When given a choice between lab chow in the form of chunks or powder, both controls and DMNL rats ate similar amounts of lab chow powder while DMNL rats ate less lab chow chunks. Total caloric consumption was the same as on chunks alone. When returned to lab chow chunks as the only source of calories, the pattern and magnitude of intake was again depressed for the DMNL rats. When offered a choice between Ginger Snaps cookies in chunk form versus powder, DMNL rats remained hypophagic in terms of chunk consumption while the intake from powder was similar in both controls and DMNL rats. When offered a choice between chunks of lab chow and Ginger Snaps, DMNL rats were again hypophagic on lab chow chunks, ate the same as the controls of the cookies, and the total caloric intake was of the same magnitude and pattern as observed in previous tests. The data suggest, but do not conclusively show, that DMNL rats are not hypophagic because they have an aversion to chewing hard food and that, when offered a diet similar in hardness to lab chow chunks i.e., hard cookies, will prefer the less tasty but nutritionally complete lab chow. They are apparently capable of choosing a diet for complete nutrition and, as previously reported, can meter calories competently.     

Somatic, metabolic and endocrine correlates of set point recovery in food-restricted and ad lib-fed weanling rats with dorsomedial hypothalamic lesions

Male Sprague-Dawley rats received either electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats) or sham-operations (CON), and were fed lab chow ad lib for 41 post-operative (POP) days. Subsequently one lesioned (DNML-AL) and one control group (CON-AL) continued to receive lab chow ad lib until the end of the experiment (POP day 78). A second lesioned (DMNL-RE) and control group (CON-RE) were given 80% of the amount of food eaten by their ad lib-fed counterparts for 28 days. At this time several rats from each group were killed. The remaining animals were then given lab chow ad lib for nine days and then also killed. Both DMNL-RE and CON-RE recovered their lowered body weight, food intake and feeding efficiency and showed the same pattern and relative magnitude as their ad lib-fed counterparts. Similarly, carcass lipid, epididymal fat pad lipid, incorporation of glucose-U-C14 into fat pad saponifiable lipid, total lipid, total glycogen (DPM/protein), liver protein, incorporation of glucose into liver CO2 and concentrations of plasma glucose, glycerol, triglycerides and free fatty acids normalized on refeeding to the same extent and in the same pattern in DMNL-RE as in CON-RE. In contrast to previous studies, plasma insulin was lower in DMNL-AL than in CON-AL but DMNL-RE and CON-RE had similar levels on refeeding. Also on refeeding, both DMNL-RE and CON-RE showed the same enhanced glucose incorporation into liver total lipid. The data show that DMNL rats, although smaller in size and hypophagic in absolute terms, recovered lost body weight--at least under our relative mild reduction of 80% of their ad lib-fed controls--with the same competence and in the same time interval as sham-operated controls. It is quite possible that a more severe restriction of body weight would have uncovered some deficits in DMNL rats, however. Under the constraints of the present experimental arrangement, the data strengthen previous evidence for the existence in DMNL rats of an "organismic" set point that makes for a "scaled-down" but homeostatically normal animal.     

Role of intrahypothalamic insulin in circadian patterns of food intake, activity, and body temperature.

These experiments examined the extent to which chronic intrahypothalamic (IH) insulin infusions that alter circadian patterns of food intake (FI) affect the regulation of other diurnally varying behavior in the rat. One-week IH insulin infusion (1.5 microU/hr) significantly decreases rats' night FI and increases day FI but does not alter the diurnal pattern of activity. Mean daily core temperature increased slightly but significantly during insulin infusion, the daily peak of the body temperature rhythm did not shift significantly, and the daily range of body temperature increased. IH insulin infusion in rats living in constant light and thus without circadian rhythm of FI led to significant decreases in FI and body weight. These data support the conclusion that IH insulin infusion alters food intake and body weight through a specific effect on a neural system that regulates food intake and body weight, and not by altering circadian rhythms.