Effect of guanethidine sympathectomy on intake and body weight of intact and LHA-lesioned rats

The present study investigated the role of direct sympathetic nervous system innervation of the viscera in the reduced body weight levels maintained by animals bearing lesions of the lateral hypothalamic area (LHA). Adult, male rats with, and without, electrolytic lesions of the (LHA) were treated with guanethidine sulphate (25 mg/kg IP daily for 6 weeks) to produce destruction of the peripheral sympathetic nervous system. LHA-lesioned rats displayed the expected reduced body weight compared to intact rats. Sympathectomy in lesioned rats resulted in an identical pattern of effects to that seen in intact rats. Transitory reductions in intake were effected and weight was significantly depressed by one week of guanethidine treatment. However, weight had recovered to control levels in both intact and lesioned drug-treated groups by the end of the experiment. The reduced body weight level maintained by LHA-lesioned rats was not altered by guanethidine sympathectomy. The major conclusions are (1) the reduced body weights maintained following LHA lesions are not dependent upon an intact sympathetic nervous innervation of visceral organs, and (2) peripheral sympathectomy in intact adult rats has no chronic effects on either body weight or food and water intake.     

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.     

Effect of interscapular brown adipose tissue denervation on body weight and feed efficiency in alcohol drinking rats

In rats, chronic alcohol intake increases energy expenditure and enhances interscapular brown adipose tissue (IBAT) mass and activity. It is known that alcohol intake is mainly preprandial. In man, alcohol intake during a meal increases postprandial thermogenesis. Since diet-induced thermogenesis is mediated by the sympathetic nervous system, the effect of IBAT surgical denervation was examined on body weight (BW), food intake (FI) and feed efficiency (FE) in alcohol drinking rats. Alcohol drinking rats gained significantly less BW than water drinking rats; FI was identical and so FE was less in alcohol-treated animals. After sympathectomy, the water drinking group was identical to its own control group for BW gain, FI and FE. BW gain of sympathectomized drinking rats was significantly higher than that of controls. FI and FE were nearly identical. It is concluded that the increase in thermogenesis observed in chronic alcohol-treated rats is partly suppressed by sympathectomy. This increase could also involve other BAT mass and other tissues in the whole rat.     

Meal patterns and glucoprivic feeding in the guanethidine-sympathectomized, adrenodemedullated rat

The feeding behavior of rats sympathectomized by neonatal administration of guanethidine (GUA) and/or adult adrenal demedullation (MDL) was investigated. GUA treatment tended to decrease body weight gain and food intake, chiefly by decreasing meal size and increasing satiety ratios. It also attenuated the increase in food intake caused by 2-deoxy-D-glucose (2DG; 150, 300, 450 mg/kg, IP) but not by insulin (3, 6, 9 U/kg, IP). MDL altered meal patterns in the same manner as GUA treatment but the effects were of smaller magnitude. It did not influence the response to either glucoprivic challenge. Combined GUA treatment and MDL generally produced additive effects. These results suggest that the major sympathetic influence on feeding is through adrenergic innervation and not circulating catecholamines. The hypothesis that the alteration in feeding patterns produced by ventromedial hypothalamic lesions is due to decreased sympathetic activity was not supported.     

Caloric compensation in rats with combined lesions in lateral and ventromedial hypothalamus

Compensatory adjustment of caloric intake in response to stomach loading of glucose or vegetable oil was studied in rats with lateral hypothalamic (LH) or with combined lateral and ventromedial hypothalamic (VMH) lesions. The LH lesioned rats as well as the sham operated controls compensated the loaded calories by an adequate reduction of oral intake, but those bearing both LH and VMH lesions tended to undercompensate with increased total caloric intake and body weight during some but not all periods of loading. Some of the rats with combined LH and VMH lesions displayed characteristics of the respective syndrome, such as thirst deficit and hyperphagia.     

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.     

The effect of ambient temperature on rectal temperature,food intake and short term body weight in the capsaicin desensitized rat

1. .Subcutaneous injections of capsaicin (mean cumulative dose: 80.1±3.6 mg·kg^?1) permanently reduced the capacity of rats to withstand a hot environment when deprived of water. With water available, hyperthermia was discrete or absent in capsaicinized rats in hot environment.
2. Desensitization was followed by a significant decrease in both food intake and body weight. Treated rats recovered normal body weight after 3 weeks.
3. In a hot environment, compared to controls, food intake was significantly increased in capsaicin desensitized rats which maintained their body weight. In cold environment, food intake was decreased in capsaicin desensitized rats which lost body weight. At normal ambient temperature, food intake and body weight were similar in the 2 groups.
4. Caloric intake adjustment at high and at low temperatures was therefore disturbed in capsaicin desensitized rats. It is concluded that hypothalamic thermodetectors implicated in both thermoregulation and food intake behaviour could be partially damaged by capsaicin.

     

Effects of selective estrogen receptor agonists on food intake and body weight gain in rats

Ovariectomized (OVX) rats eat more and gain weight more rapidly than sham-operated (SO) rats and estradiol (E(2)) treatment attenuates food intake and body weight gain in OVX rats. Studies were designed to test the hypothesis that the alpha subtype of the estrogen receptor (ERalpha) mediates the attenuating effects of E(2) on food intake and body weight gain while the beta subtype (ERbeta) mediates opposing actions that lead to increased food intake and body weight gain. Female rats were SO or OVX and treated daily with vehicle (dimethylsulfoxide, DMSO) or E(2) (10 microg/day), or the ERalpha-selective agonist, 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 0.5 mg/day), or the ERbeta-selective agonist, 2,3-bis(4-hyroxyphenyl)-propionitrile (DPN, 0.5 mg/day) for 14 days. Total food intake was significantly reduced by E(2) and PPT, but not DPN. Total body weight gain was significantly increased in OVX rats compared to SO rats and treatment with E(2) or PPT, but not DPN, significantly decreased total body weight gain to levels that were not significantly different from SO rats. A dose-response study of PPT indicated that at 0.25 mg/day, PPT significantly reduced total 21-day food intake and body weight gain and, at 0.13 and 0.06 mg/day, PPT significantly reduced total body weight gain compared to OVX rats without significantly reducing total food intake. A dose-response study of DPN indicated that none of the three doses of DPN significantly altered total 21-day food intake or total body weight gain. These results suggest ERalpha mediates the attenuating effects of estrogens on food intake and body weight gain while ERbeta has no effect on these variables.     

The control of puberty in the dietary restricted female rat

Food intake, body weight and serum LH, FSH, progesterone and oestradiol-17 beta were monitored from weaning to puberty in fully fed females housed in groups of four or individually and in females individually housed and dietary restricted. Restriction of food intake from weaning delayed the onset of puberty (34-39 days fully fed, 63-189 days dietary restricted) which was achieved at the same body weight as in the fully fed females. Individual housing of fully fed rats resulted in a significant increase in relative and absolute food intake (but not body weight) and a decrease in serum FSH when compared to group housed fully fed animals. Serum FSH and progesterone were significantly decreased in restricted females and serum oestradiol-17 beta significantly increased.     

Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat

In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose-dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged.     

Defense of a lowered weight maintenance level by lateral hypothamically lesioned rats: Evidence from a restriction-refeeding regimen

Male rats maintained their body weight at approximately 85% that of sham-lesioned controls following lesions of the lateral hypothalamus (LH). One month following surgery, the food intake of half the LH-lesioned animals was restricted until their body weight had declined to 80% that of nonrestricted LH animals. Half the sham-lesioned animals were similarly restricted until their body weight fell to 80% that of nonrestricted control animals. When returned to an ad lib feeding schedule, both restricted groups were initially hyperphagic and quickly restored their body weights to the level of the nonrestricted group from which they were originally selected. In doing so, the LH animals increased their food intake by the same amount and took the same number of days to restore their weight to control levels as the sham-lesioned animals. These observations provide further evidence of the vigor and effectiveness with which LH animals defend their reduced level of maintained body weight.     

Effects of beta-adrenergic blockade on lateral hypothalamic lesion-induced thermogenesis

Oxygen consumption is markedly elevated in rats with lesions of the lateral hypothalamus (LH), a response typically associated with hyperactivity. To test for involvement of adrenergic systems in this hypermetabolic state, propranolol was administered before and immediately after LH lesions. Propranolol attenuated both the lesion-induced rise in oxygen consumption and activity in the 12 h after surgery. A second experiment evaluated the contribution of activity to this thermic response by lesioning rats immobilized by a continuous barbiturate infusion. The persistence of lesion-induced increases in oxygen consumption in the absence of activity and the attenuation of this response by propranolol demonstrated that 1) LH lesions directly alter metabolic heat production, and 2) this effect is at least partly mediated by beta-adrenergic systems. The functional significance of increased energy expenditure after LH lesions is discussed in light of the known effects of this lesion on the level of regulated body weight.     

Vanadate stimulates in vivo glucose uptake in brain and arrests food intake and body weight gain in rats

Vanadate, administered via drinking fluid (0.2-0.8 mg/ml in 80 mM NaCl), attenuated food intake and strongly suppressed body weight gain in normally-fed or 20-hour food-deprived rats. At 0.8 mg/ml for 4 days, oral vanadate significantly stimulated the rate of hexose uptake by brain tissue. When microinjected into the lateral cerebral ventricle at a dose of 82 nmol, vanadate strongly and specifically suppressed food intake and body weight gain in 20-hour food deprived rats previously maintained on tap water. This inhibitory effect was reversed by coadministration of 3-O-methyl glucose. Collectively, the results suggest that vanadate is capable of blocking food intake by a specific effect in the central nervous system that involves stimulation of local glucose uptake.     

Sleep, brain energy levels, and food intake

Background

The feeling of hunger and feeding, a wake–state-dependent behavior, is regulated by specific centers within the hypothalamus. While paraventricular nucleus (PVN), arcuate nucleus (ARC), and dorso- and ventromedial hypothalamus (DMH/VMH) regulate feeding, the lateral hypothalamus (LH) is associated both with feeding and wake/REM sleep regulation. In order to examine the effects of sleep and wakefulness on food intake and body weight, we also measured hypothalamic ATP concentrations, which are known to be involved in feeding behavior and sleep–wake regulation.

Methods

In rats, food intake and body weight was measured during a 24-h light–dark cycle and during 6 h of sleep deprivation (SD) performed by gentle handling. Tissue samples from the PVN, ARC/DMH/VMH, and LH were collected after 6 h of SD and from time-matched diurnal controls. ATP was measured by luciferin-luciferase bioluminescence assay.

Results

Across the 24-h light–dark period, rats consumed approximately 28.13±4.48 g of food and gained 5.22±1.65 g with a positive correlation between food intake and body weight. During SD, while food intake increased significantly +147.31±6.13%, they lost weight significantly (–93.29±13.64%) when compared to undisturbed controls. SD resulted in a significant decrease in ATP levels only in LH (–44.60±21.13%) with no change in PVN, ARC/DMH/VMH region when compared with undisturbed controls.

Conclusion

The results indicate a strong overall correlation between ATP concentrations in the LH and individual food intake and suggest a sleep–wake dependent neuronal control of food intake and body weight.     

Weight loss,slower growth and lower fasting heat production rates following LH lesions in female rats

Lesions in the lateral hypothalamus (LH) can result in a permanent loss of body weight and slower growth in female rats, but do not do so invariably. Weight and growth rate changes were always accompanied by lower rates of fasting heat production (FHP) independent of changes in activity. The thyroids of these animals were significantly below normal in size. None of the traditional deficits of the “LH syndrome” were present: the animals ate when deprived of water: drank when deprived of food (although less than the control animals) and increased their food intakes when injected systemically with insulin, at least on the initial test. With repeated tests the food intake following insulin-induced hypoglycemia declined both in the animals with lesions and in the animals whose body compositions and weights had been lowered to the same levels.     

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.     

Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats

Ovariectomy-induced increases and estradiol-induced decreased in body weight cannot be fully accounted for by changes in energy intake and appear to reflect alterations in thermogenesis. Because changes in energy expenditure have been linked to altered sympathetic nervous system (SNS) activity in brown adipose tissue (BAT), the role of estradiol in thermogenesis and body weight, as mediated by the SNS innervation of interscapular BAT (IBAT), was examined. The IBAT of ovariectomized rats was bilaterally or unilaterally surgically denervated. The chow-fed, bilaterally denervated group gained more weight than the unilaterally denervated or sham-operated group, an effect that was exaggerated by sucrose feeding. Food intake did not differ among the groups within each dietary condition. Estradiol benzoate (EB) injections decreased body weight in all groups. Bilateral, and to a lesser extent, unilateral IBAT denervation blocked the EB-induced increase in thermogenesis. Treatment with EB increased IBAT wet weight regardless of surgical treatment. Because IBAT denervation markedly decreased lipoprotein lipase activity and fatty acid synthesis/uptake, the estradiol-induced increase in denervated IBAT wet weight is most likely due to decreased lipolysis produced by the surgical sympathectomy. These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism.     

Effect of lateral hypothalamic lesion on brown adipose tissue of Zucker lean and obese rats

Acute (10-day) lateral hypothalamic (LH) lesion induced a reduction of food intake in both lean and obese Zucker rats which averaged about 50% over the course of the first 10 days. The aphagia associated with a fall in body weight in both genotypes which was greater than their respective pair-fed controls, indicating a change in energetic efficiency. The reduced level of BAT protein, mitochondria and GDP binding observed in the obese rat was restored after LH lesion, suggesting the reestablishment of a normal sympathetic drive to the tissue. The markedly lower plasma insulin concentration in the LH lesioned obese rat is consistent with a reduction in parasympathetic activity in these animals. Food restriction in the sham lean rat reduced BAT protein content and mitochondrial GDP binding, whereas no such changes were observed in the food restricted obese rat. This demonstrates the insensitivity of the obese rat to dietary signals and may imply that LH lesion restores diet-induced BAT thermogenesis in the obese rat.     

Overeating and obesity produced by interruption of the caudal connections of the hypothalamus: evidence of hormonal and metabolic disruption.

Surgical transection of the posterior connections of the medial basal hypothalamus is much more effective in producing hyperphagia and obesity in female than in male rats. The hyperphagia of female rats can be attenuated by daily injections of estradiol. When starved to the weight of control animals, previously obese female rats with cuts through the posterior hypothalamus showed only mild hyperphagia but quickly returned to their elevated body weights. The results indicated that hormonal and metabolic disturbance are important factors in determining food intake and body weight following damage to the ventromedial hypothalamus.