Evidence of incomplete behavioral sexual differentiation in obese male Zucker rats

Genetically obese male Zucker rats displayed lower rates of intromission behavior and ejaculated in significantly fewer tests than lean Zucker littermates. After castration and daily injections of a low dosage (5 micrograms/kg) or estradiol benzoate (EB) followed by progesterone (1 mg/kg), obese males displayed significantly higher lordosis quotients than lean controls. Continued daily administration of higher (10, 15 micrograms/kg) dosages of EB followed by progesterone caused significant reductions in lordotic responsiveness in obese males but not in lean controls. Thus, deficient masculine coital performance was correlated with altered receptive responsiveness to ovarian steroids in obese Zucker male rats. This suggests that the sexual differentiation of the developing brain may be deficient in obese Zucker males.     

Insulin stimulates inositol incorporation in hippocampus of lean but not obese Zucker rats

We have previously reported that intraventricular insulin is ineffective in decreasing the body weight of obese (fa/fa) Zucker rats. In the present study, we report that insulin at concentrations of 1 and 5 nM significantly stimulates incorporation of 3H-myoinositol into inositol phosphates (29 +/- 5% and 20 +/- 6% stimulation over control levels) and membrane inositol lipids (29 +/- 4% and 20 +/- 6% stimulation over control levels) within hippocampal slices from lean (Fa/Fa) Zucker rats (n = 3 preparations). Smaller but significant stimulations were observed in the Fa/fa Zucker rat (n = 5) hippocampus [10 +/- 3 and 13 +/- 4% stimulation over control levels (inositol phosphates) and 10 +/- 4 and 14 +/- 3% stimulation over control levels (inositol lipids) with 1 and 5 nM insulin]. Insulin had no effect on 3H-inositol incorporation into hippocampal slices from obese (fa/fa) Zucker rats (n = 5). No difference in insulin binding to hippocampal membranes was observed among the three genotypes. These findings confirm the behavioral observation of insulin insensitivity within the fa/fa Zucker CNS and suggest that this insensitivity may be gene-dose-related.     

Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity

To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.     

Molecular and morphometric description of adipose tissue during weight changes: a quantitative tool for assessment of tissue texture

The aim of this study was to evaluate the morphometric changes of adipose tissue of lean and obese rats as assessed by computerized image analysis (IA) system in experimental conditions, with different degrees of adiposity. Moreover, to validate measures obtained by image analysis by correlation with direct measures of adiposity (body weight, epididimal fat, mean fat cell size and serum leptin). Finally to correlate these changes to expression of genes involved in lipid deposition and mobilization in adipose tissue. Lean (Fa/?) and genetically obese (fa/fa) Zucker rats were studied. Obese rats were food-restricted or treated with retinoic acid (ATRA) in order to reduce body weight and fat content. Moreover, gene expression of two key enzymes involved in fat metabolism (HSL and DGAT) were assessed in adipose tissue by RT-PCR. Our results show that HSL expression in adipose tissue was lower in obese compared to lean rats (1.47+/-0.02 vs 0.35+/-0.03, p<0.005) and was upregulated during food restriction in obese rats. DGAT expression was similar in lean and obese rats and was reduced by treatment with ATRA in obese rats. Tissue texture assessed by IA was significantly higher in lean compared to obese rats (23.2+/-0.6 vs 11.6+/-2.4%; p=0.01). Tissue structure highly correlated with adiposity in obese rats with different amount of body fat (area fraction vs epididimal fat depot: p=0.001). Distribution of measures for each sample, an index of spread of adipose tissue texture, as expressed by the standard deviation, correlated with adiposity (standard deviation vs epididimal fat depot: p=0.002) thus suggesting that adipose tissue texture increases its heterogeneity when adiposity is lower. This observation is in agreement with the hypothesis that the process of lipid mobilization from adipose tissue is not uniform, but a subpopulation of slimming adipocytes undergoes a complete release of their fat content while the rest of the tissue is much less affected. Moreover, image analysis system seems a reliable quantitative tool for assessment of adipose tissue texture.     

Marked enhancement of noradrenaline turnover in extensive brain regions after activity-stress in rats

Male Wistar rats were exposed to a 5-day activity-stress procedure wherein animals were housed in running-wheel activity cages and fed for only 1 hr each day (wheel-housed/food-restricted rats). This activity-stress procedure produced marked elevation in levels of the major metabolite of noradrenaline (NA), 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO₄), in eight brain regions, while a reduction of NA level occurred in several of these brain regions. These rats also exhibited excessive running activity and developed severe gastric glandular ulcers. Rats fed ad lib and housed in activity cages (wheel-housed/ad lib-fed) and rats housed in standard individual cages and which received either 1-hr daily feeding (control cage-housed/food-restricted) or ad lib feeding (control cage-housed/ad lib-fed) showed neither significant changes in brain NA metabolism nor gastric ulcers. These results suggest that the interaction of a restricted feeding regimen and an increase running wheel activity caused marked enhancement of NA turnover in several brain regions, which is one of the neurochemical mechanisms underlying the physiological and behavioral changes produced by the activity-stress paradigm.     

Nociception and opioid-induced analgesia in lean (Fa/-) and obese (fa/fa) Zucker rats

Previous research indicates a possible interrelationship between the endogenous opioids (EO), nociception and food-intake. We therefore considered the hyperphagic obese Zucker rat a good candidate for abnormal responses to nociceptive stimuli. Pairs of lean and obese sisters were tested for latency of response to nociceptive stimuli by tail-flick and tail-pinch methods. Obese rats exhibited shorter latencies in each test, (tail-flick, p less than 0.05 and tail-pinch, p less than 0.001). Dose/response curves for morphine analgesia indicate that morphine is less potent in obese than in lean rats (ED50's = 4.87 +/- 0.62 mg/kg and 3.12 +/- 0.41 mg/kg respectively, p less than 0.05). These data suggest a defect in the EO systems of obese Zucker rats.     

Metabolic characteristics of skeletal muscle from lean and obese Zucker rats

The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO2, but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO2 or in incorporation into lipid (both soleus and EDL muscles), except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform changes in metabolism between muscles of the obese rats.     

Rejuvenating effects of 10-week underfeeding period on estrous cycles in young and old rats

The effects of providing 50% of normal feed intake for 10 weeks followed by 16 weeks of ad lib feeding on estrous cycles and mammary tumor incidence were studied in female rats initially 4 months and 15-16 months old. Initially all young rats exhibited regular or irregular estrous cycles and only about 41% of the older rats cycled regularly or irregularly; the remainder of the older rats did not cycle. During underfeeding, both the young and older rats lost body weight and ceased to cycle. After refeeding 100% of both young and old rats resumed cycling, the young rats for a much longer period than the old rats, and more of both groups continued to cycle than their ad lib-fed controls. Upon refeeding, the young and old rats reached the body weights of the ad lib-fed controls in about 3 weeks. Mammary tumors were initially present only in old rats and regressed during underfeeding; they rapidly reached control size upon refeeding. Plasma PRL levels declined during underfeeding but rebounded to higher than control values upon refeeding in both young and old rats. In young but not in old rats, plasma LH levels fell during underfeeding but returned to control values upon refeeding. These results demonstrate that a relatively short period of underfeeding, followed by refeeding, can delay the decline in reproductive cycles in young rats and reinitiate estrous cycles in older rats. These effects appear to be mediated via the neuroendocrine system.     

Interrelationships among activity,food intake and weight gain in genetically obese and lean Zucker rats

In Experiment 1, food deprivation resulting in a 30% reduction in body weight produced significant increases in wheel running in both obese and lean female Zucker rats. In Experiment 2, a new technique, food contingent activity (FR, VI), dramatically increased wheel running in both obese and lean female Zucker rats. This increase in activity was achieved primarily during the dark period. Regardless of changes in activity levels, food intake and body weight gain remained similar to controls. When food was again available ad lib, activity levels rapidly decreased for obese but not lean rats. These results indicate that behavioral interventions alone are not sufficient to correct the obesity of the genetically obese rat.     

Effect of CCK antibodies on food intake and weight gain in Zucker rats

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n = 12, 192 +/- 16 g) and lean (n = 12, 152 +/- 11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p less than 0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p less than 0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p less than 0.04 and p less than 0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased sensitivity of Zucker obese rats to naloxone is present at weaning

Increased pituitary and plasma concentrations of opioid peptides in genetically obese rodents may be a cause or consequence of obesity. It has been shown that food intake is decreased more in adult genetically obese rats and mice than lean rats and mice by administration of naloxone, an opiate antagonist. Evidence for an opiate-mediated component in the development of rather than the consequence of obesity would be provided if young, not yet obese, genetically obese rats were more sensitive than lean rats to naloxone. In the present experiment two groups of male and female obese and lean Zucker rats, fasted for 2 hr before the onset of the dark portion of the 12-hr light-dark cycle, were administered 0.125 to 0.5 mg/kg naloxone or 0.5 to 2.0 mg/kg naloxone subcutaneously and 30- and 60-min food intakes were measured. In the group administered the lower doses of naloxone, obese rats of the three ages tested responded more than the lean rats after 30 min (70 vs. 79% of control, p less than 0.02). However, increased sensitivity occurred during the 0-60 min period in rats 4-5 weeks old and 0-30 min period in rats 8-9 and 12-13 weeks old. In the second group tested with the higher doses, the obese responded less than the lean rats (73 vs. 66% of control, p less than 0.05) and there was no difference in response after 0-60 min (66 vs. 61% of control, NS). Thus, increased sensitivity to threshold doses of naloxone occurs before the development of substantial obesity and therefore opiate peptides may play a causal role in obesity.     

Decreased pancreatic CCK receptor binding and CCK-stimulated amylase release in Zucker obese rats

In Zucker obese rats the response to the effects of CCK on food intake and pancreatic exocrine function are decreased. However, it is unknown whether the decreased responsiveness is due to decreased receptor number and/or sensitivity or abnormal circulating concentrations of CCK. In these experiments percent total binding of 125I-CCK-33 to pancreatic acini from obese rats was one-half that in lean rats when data was expressed on a per microgram DNA basis (19.6 +/- 5.1 vs. 47.4 +/- 11.4, p less than 0.01). In a second experiment while the maximally effective dose of CCK for stimulating amylase secretion from dispersed pancreatic acini was similar in obese and lean rats (10(-10) M), less amylase was secreted in obese rats across the dose range tested (p less than 0.001). In contrast, carbachol had similar potency and efficacy in stimulating amylase release from obese and lean pancreatic acini. The increase of pancreas size by use of a trypsin inhibitor was greater in lean than obese rats (p less than 0.03). In addition, stimulation of amylase release by CCK from obese trypsin inhibitor-treated compared with control obese rats was greater than that from lean trypsin inhibitor-treated compared with control lean rats (p less than 0.002). However, overall, stimulation of amylase secretion by CCK was only 36% of control (p less than 0.001) and by carbachol was only 20% of control (p less than 0.001). Thus, increased size by increased cell number was associated with decreased response per cell.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of estrogen, testosterone and progesterone on partner preference, receptivity and proceptivity

The influence of Estradiol benzoate (EB), Testosterone propionate (TP) and Progesterone (P) on the female's partner preference for sexually active males was investigated and compared to levels of receptive and proceptive behaviors observed in a tethered male test situation. Doses of EB (1 micrograms), TP (500 micrograms) and P were selected on the basis of previous investigations indicating that female rats treated with these dosages will show comparable levels of lordosis behavior. The results indicate that TP stimulates partner preference for sexually active males over estrous females in ovariectomized female rats. Females treated with EB tended to prefer the company of sexually active males more than Oil-treated females and less and TP-treated females. However, preference behavior of EB-treated females was not significantly different from that of Oil- or TP-treated females. Additional treatment with P (100 micrograms) did not influence partner preference of Oil-, EB- or TP-treated females. In the tethered male tests, P stimulated proceptivity of EB- or TP-treated females and receptivity of EB-treated females. Significant differences in proceptive and receptive behaviors between EB- or TP-treated were not found. Although facilitation of receptive and in particular, proceptive behaviors were found to be generally accompanied by an increased partner preference for males, it is concluded that gonadal hormones are differentially affecting aspects of female rat sexuality: Relative to the activation of receptive behavior, TP was found to be more effective (than EB) to increase preference for a male; P (given to EB- or TP-treated females) was found to stimulate receptive and proceptive behaviors considerably, while being ineffective to stimulate preference for a male.     

Abnormal brown adipose composition and beta-adrenoceptor binding in obese Zucker rats

The composition, morphology, beta-adrenergic receptor binding, and in vitro lipolysis were examined in lean and obese, 5- to 6-mo-old male Zucker rat interscapular brown adipose tissue (IBAT). IBAT pads from obese rats were heavier (283%), had more lipid (700%), and more (75%)( and larger (83%) adipocytes than those from lean rats. Also, IBAT from obese rats had no multiloculated cells, and 50% of their IBAT adipocytes were the size of white fat cells. High affinity binding for (-)-[3H]dihydroalprenolol (KD, 15-18 nM), as well as the estimated KD values for binding and the 1/2 Vmax values for adrenergic agonist-induced lipolysis were similar in isolated IBAT cells from lean and obese rats. However, adipocytes from IBAT in obese rats had 75% fewer high affinity beta-adrenergic binding sites per cell (Bmax) compared to those in lean rats. These findings are most compatible with the infiltration of IBAT by white adipocytes. Such infiltration would be expected to reduce the overall thermogenic capacity of IBAT in obese Zucker rats and thereby contribute to the maintenance of their obesity.     

Decreased pancreatic exocrine response to cholecystokinin in Zucker obese rats

Cholecystokinin (CCK), one of the peptides secreted by the gastrointestinal tract during a meal, stimulates release of enzymes into pancreatic juice and is a trophic hormone for the pancreas. Administration of CCK also decreases food intake, and obese rats have been shown to have a higher threshold than lean rats for this apparent effect on satiety. In this study experiments were designed to compare the sensitivity of obese and lean rats to the effects of CCK octapeptide (CCK-8) on pancreatic structure and exocrine function. In both growing and adult Zucker rats DNA content of the pancreas from obese rats was decreased compared with that from lean rats [2.42 +/- 0.21 vs. 3.07 +/- 0.18 mg (P less than 0.01) and 2.46 +/- 0.25 vs. 3.01 +/- 0.19 mg (P less than 0.05), respectively], and in adult obese rats this was accompanied by decreased pancreas size on both absolute weight and percent of body weight bases. In adult obese Bar Harbor mice, although DNA content of the pancreas was also decreased [1.70 +/- 0.10 vs. 2.41 +/- 0.11 mg (P less than 0.01)], pancreas weight was not different (0.30 +/- 0.01 vs. 0.32 +/- 0.01 g). In young rats growth of the pancreas was stimulated by 2 micrograms/kg CCK-8 administered subcutaneously or 100 mg/kg of a trypsin inhibitor administered orally twice daily for 2 wk. Although both treatments increased weight and DNA and protein content of the pancreas, the increases in DNA and protein content were smaller in obese than lean rats, indicating a decreased responsiveness to both trophic agents. Administration of CCK-8 stimulated smaller increases in pancreatic juice volume and amylase release in obese compared with lean rats, indicating decreased pancreatic exocrine function in response to CCK. In adults the CCK-8 dose-response curve for amylase release from dispersed pancreatic acini of obese rats was similar to that of lean rats, indicating normal sensitivity in vitro. Thus, in obese rats and mice DNA content of the pancreas is decreased when compared with that of lean rats and mice, and this is accompanied by decreased in vivo responses to CCK in obese rats.     

In-Situ Mechanical Characteristics of the Tongue are not Altered in the Obese Zucker Rat

Study Objectives:

Obese Zucker rats have more collapsible isolated upper airways, compared with their lean counterparts. The functional characteristics of the tongue as a potential mechanism for the enhanced upper airway collapsibility in the obese Zucker rat are unknown. This study measured the functional characteristics of the tongue muscle in lean and obese Zucker rats.

Design:

In-situ tongue force (twitch and peak) and fatigability were measured in anesthetized obese and lean Zucker rats.

Setting:

Animal housing facility at the University of Buffalo.

Subjects:

Eight lean and eight obese Zucker rats.

Intervention:

Tongue force and fatigability were measured before, during, and following cocontraction of the tongue protrudor and retractor muscles via direct stimulation of the common hypoglossal nerve.

Measurements and Results:

Obese rats were significantly heavier than their lean counterparts (718 ± 101 gm vs. 545 ± 32, P < 0.05). Total force production at all stimulation frequencies was not different between lean and obese Zucker rats before or after fatigue (P = 0.436). Forces were significantly reduced at the end of the 5-minute stimulation period (P < 0.001) and returned to baseline within 1 minute after fatigue in both lean and obese rats. At the end of the fatigue protocol, tongue force averaged 63.3% ± 13.8% and 72.3% ± 17.8% of the initial force in obese and lean rats respectively (P = 0.85).

Conclusion:

Obesity does not alter the in-situ force production of the tongue muscle. Thus, increases in collapsibility of the isolated upper airway previously noted in obese Zucker rats cannot be ascribed to upper airway muscle dysfunction or enhanced fatigability.

Citation:

Ray AD; Farkas GA; Pendergast DR. In-situ mechanical characteristics of the tongue are not altered in the obese Zucker rat. SLEEP 2009;32(7):957-961.     

Sympathoadrenal function in genetically obese Zucker rats.

The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in blood samples taken through a permanent heart catheter before, during, and after exercise or intravenous infusion of E and NE. Baseline plasma FFA and insulin levels were markedly increased in the obese animals. Exercise, i.e., strenuous swimming against a counter current for 15 min, led to reduction of plasma insulin concentrations and an increase of all other blood components in lean Zucker rats. In obese animals, an exaggerated increase of blood glucose and a large suppression of plasma insulin occurred. Plasma FFA levels tended to decline during exercise. Plasma catecholamine patterns in the exercising fatty Zuckers were not different to those of the lean animals. Infusion of E caused an increase of blood glucose and a decrease of plasma insulin concentrations in both groups of animals. The increase in blood glucose in the obese animals was significantly larger compared to the changes in the lean animals. Infusion of NE significantly reduced plasma insulin concentration in obese but not in lean animals. The results revealed that activation of the sympathetic system, expressed as exercise-induced alterations in plasma E and NE levels, is normal in obese Zucker rats. However, postsynaptic receptor effects of catecholamines on glycogenolysis and lipolysis are different in obese and lean animals, which points to permanent changes in adrenoceptor mechanisms on adipocytes, hepatocytes, and muscle cells in obesity.     

The effect of leptin receptor deficiency and fasting on cannabinoid receptor 1 mRNA expression in the rat hypothalamus, brainstem and nodose ganglion

Despite ample evidence for the involvement of the endocannabinoid system in the control of appetite, food intake and energy balance, relatively little is known about the regulation of cannabinoid receptor 1 (CB₁R) expression in respect to leptin signalling and fasting. In the present study, we examined CB₁R mRNA levels in lean (Fa/?) and obese (fa/fa) male Zucker rats under basal and food-restricted conditions. Using stereological sampling principles coupled with semi-quantitative radioactive in situ hybridization we provide semi-quantitative estimates of CB₁R mRNA expression in key appetite regulatory hypothalamic and brainstem areas, as well as in the nodose ganglia. Whereas no effect of fasting were determined on CB₁R mRNA levels in the paraventricular (PVN) and ventromedial hypothalamic (VMH) nucleus, in the brainstem dorsal vagal complex or nodose ganglion of lean Zucker rats, CB₁R mRNA levels were consistently elevated in obese Zucker rats pointing to a direct influence of disrupted leptin signalling on CB₁R mRNA regulation.     

Feeding response of weanling zucker obese rats to cholecystokinin and bombesin

Zucker weanling obese rat meal size is greater than in lean litter-mates by 4 weeks of age, indicating a possible decreased sensitivity to satiety signals. Adult Zucker obese rats are less sensitive to the putative satiety signal octapeptide of cholecystokinin (OP-CCK) when injected after a normal intermeal interval. In these experiments were compared responses of Zucker lean and obese rats from 3–11 weeks of age to OP-CCK and bombesin (BBS), another recently reported putative satiety agent. Injection of 2.0 and 4.0 μg/kg OP-CCK in 4–5 week olds had no effect on food intake of obese rats while decreasing 60-min food intake in lean rats 29 and 28 percent, respectively. However, 8.0 μg/kg OP-CCK decreased food intake of obese and lean rats similarly, indicating decreased, rather than lack of, sensitivity in the obese. The doses of 2.0 and 4.0 μg/kg BBS decreased food intake similarly in the obese and lean rats, but 1.0 μg/kg, although having no effect in lean rats, increased food intake in obese rats approximately 17 percent. Thus, while Zucker obese weanling rats appear to be less sensitive to OP-CCK, shown to decrease food intake in lean rats, they appear to be equally sensitive to the satiety effect of similar doses of BBS, but at low doses BBS stimulated food intake in obese but not lean rats.     

Bulbectomy and sensitivity to estrogen: Anatomical and functional specificity

In order to clarify the influence of the olfactory system on female sexual behavior, ovariectomized rats were given sham operations (SHAM), total bilateral olfactory bulbectomy (TBULBX), partial bulbectomy (PBULBX), anterior olfactory nucleus lesions (AON) or accessory olfactory bulb lesions (AOB), and tested for lordosis behavior. Only TBULBX resulted in increased sensitivity to estradiol benzoate (EB) in that lordosis quotients (LQ) were increased and rejection behavior decreased following administration of 2, 4 or 8 μg EB/kg/day for 3 days. Only TBULBX group rats were anosmic on 2 postoperative tests. TBULBX group rats showed very mild hyperresponsiveness on an emotionality test. Effects of TBULBX on LQ are not due to general sensory hyperresponsiveness or EB-induced hyperresponsiveness since no differences in the quality of lordosis occurred, and no differences occurred in latency to paw-lift on hot plate tests with or without EB. Heightened EB sensitivity in the TBULBX group is not due to adrenal steroids since following adrenalectomy and 8 μg EB/kg treatment, TBULBX group LQ scores were still elevated relative to those of SHAM controls. The LQ scores of PBULBX group rats were intermediate to those of SHAM and TBULBX group rats. Bulbectomy-induced alterations in sensitivity to EB as measured by the LQ do not appear to be due to alterations in “arousal” mechanisms in general. While deficits in olfactory perception might exacerbate the effect, it is unlikely that anosmia per se is sufficient to induce major alterations in the degree of sexual receptivity following EB. The magnitude of behavioral effects of bulbectomy on EB sensitivity may be related, to some extent, to the amount of bulb tissue removed. It is possible that bulbectomy may enhance behavioral sensitivity to EB by disrupting biochemical responses to EB in limbic system structures which normally exert an inhibitory influence over sexual receptivity.