Sexual behavior of the obese male Zucker rat

Obese male Zucker rats displayed inadequate sexual behavior at four months placed with ovariectomized lean females pretreated with estrogen and progesterone. Only one out of seven obese males ejaculated during the test sessions. Diet-restricting the obese males at five months of age did not improve their sexual behavior when tested at six months of age. At ten months of age none of the obese males ejaculated during the test sessions. Lean littermates ejaculated during the sessions at all ages tested. Obese males which do ejaculate are capable of inducing pseudopregnancy in intact lean females. These findings suggest that inadequate sexual behavior is one factor contributing to the reduced reproductive capacity of obese male Zucker rats.     

Food restriction neither improves nor exacerbates reproduction in obese female Zucker rats.

Obese female Zucker rats have several reproductive abnormalities, including delayed puberty, abnormal estrous cyclicity, and behavioral hyporesponsiveness to ovarian steroid hormones. To ascertain whether excessive body weight per se causes these reproductive abnormalities, obese Zucker female rats were fed ad lib or were food restricted to match their body weights to those of lean counterparts. Food restriction neither accelerated vaginal opening nor normalized estrous cyclicity in obese female rats. Following ovariectomy, an injection of estradiol benzoate (EB, 15 microg/kg, s.c.) induced extremely low sexual receptivity in all rats, and proceptive behaviors were never observed. After treatment with EB plus progesterone (P, 2 mg/kg, s.c.), lean rats were very receptive (lordosis quotient, LQ = 94 +/- 2%) and proceptive (PRO = 12.5 +/- 2 events/min) while both ad lib-fed and food-restricted obese rats were only marginally receptive and proceptive (LQ= 19 +/- 9%, PRO = 1.8 +/- 0.7 events/min; LQ = 31 +/- 15%, PRO = 4.7 +/- 3 events/min, respectively). A higher progesterone dose (20 mg/kg) elicited vigorous sexual receptivity (LQ = 88-99%) and proceptivity (PRO = 16.5-20.4 events/min) in all EB-treated rats. Adiposity was significantly lower in food-restricted obese rats as compared to ad lib-fed obese rats (36.5 +/- 1.7% vs. 69.4 +/- 2.7%), but greater than that observed in lean rats (24.4 +/- 1.1%). These data suggest that excessive body weight per se does not underlie reproductive abnormalities in obese Zucker rats, but do not rule out the possibility that excessive adiposity may contribute to their infertility.     

Plasma testosterone levels and sexual performance of young obese male Zucker rats

The sexual behavior of obese male Zucker rats was studied at the age of 7, 8, 9, 10, 11, 14, and 16 weeks. Between 12–14 weeks of age, obese rats were treated with 400 μg testosterone propionate daily. Plasma testosterone levels were determined at the age of 10, 14, 16, and 20 weeks. Compared to lean rats, the sexual performance of the obese rats was abnormal at all ages. Plasma testosterone levels of obese rats were significantly lower at the age of 20 weeks but not at the age of 10 and 16 weeks, compared to those of their lean littermates. At the age of 14 weeks, after 2 weeks of testosterone treatment, plasma testosterone concentration rose to levels significantly higher than those of their lean littermates. However, there was no improvement in their sexual behavior following this period of hormone treatment. This study strongly suggests that obese male Zucker rats have abnormal reproductive function at all ages and that testosterone deficiency is not a primary cause of this abnormality.     

Lordosis inhibiting effects of endogenous progesterone in the male rat primed with estrogen

The aim of this study was to investigate the mechanisms involved in the inhibitory action of progesterone on estrogen-induced facilitatory effects of estradiol benzoate on lordosis behavior in the male rat. Intact adult male rats were given 1) 25 micrograms estradiol benzoate (EB) and 100 micrograms progesterone (P) at an interval of 42 hr. EB injected animals served as controls 2) EB followed by 3 doses of 400 micrograms dexamethasone (DEXA) and P as above. EB + DEXA injected animals served as controls. Testing for lordosis behavior was performed by 50 +/- hr after EB injection. A significant decrease in the number of the males displaying lordosis in response to the mounts of stimulus males resulted from P injection following EB treatment as compared to EB controls. DEXA treatment significantly reduced the number of EB animals showing lordosis responses but completely prevented the inhibitory effects of exogenous P to occur. Blood P values appeared to be significantly lower in EB + DEXA males than in their EB counterparts. The results provide evidence that endogenous P is involved in the display of lordosis behavior by EB-treated intact males. They mainly suggest that the effects of exogenous P on estrogen-induced lordosis behavior in the intact male rat result from sequential inhibitory mechanisms involving exposure of the animals to the successive action of endogenous and exogenous P.     

Chronic infusion of the amylin antagonist AC 187 increases feeding in Zucker fa/fa rats but not in lean controls

Numerous studies have established the pancreatic B-cell hormone amylin as an important anorectic peptide affecting meal-ending satiety. In the present study, we investigated the effect of a chronic infusion of the amylin antagonist AC 187 on food intake. The studies were performed using obese Zucker fa/fa rats, which are hyperamylinemic but have a defective leptin and insulin signaling system. A chronic intraperitoneal infusion of the amylin antagonist AC 187 (10 microg/kg/h) significantly increased dark phase and total food intake in Zucker but not in lean control rats. During the 8-day infusion experiment, AC 187 had no clear effect on body weight gain in either group. After acute administration, amylin and its agonist salmon calcitonin (sCT) equally reduced food intake in Zucker and lean control rats while cholecystokinin's (CCK) anorectic effect was weaker in the Zucker rats. We provide evidence for amylin being a potential long-term regulator of food intake because AC 187 increased food intake in obese fa/fa rats but not in lean control animals, which have low baseline amylin levels. Amylin may play some role as lipostatic feedback signal similar to leptin and insulin at least when the leptin and insulin feedback signaling systems are deficient. Despite basal hyperamylinemia in the Zucker rats, they do not seem to be less sensitive to the anorectic effects of amylin or its agonist sCT than respective controls. This contrasts with CCK whose anorectic action is reduced in Zucker rats when compared with lean controls.     

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.     

Effects of REM deprivation on the lordosis response induced by gonadal steroids in ovariectomized rats

Ovariectomized rats were submitted to REM sleep deprivation (REMd) using the water tank technique and their behavioral responsiveness (lordosis) to gonadal steroids was tested. In Experiment 1, animals received 2 micrograms of estradiol benzoate (EB) followed by 2 mg of progesterone (P) 44 hours later. Several REMd periods (12, 72, 96 and 120 hr) were applied, all ending four hr after P. REMd animals showed significantly lower lordosis quotients (LQ) than undisturbed sleep animals regardless of the duration of the deprivation period. In Experiment 2, animals received a single dose of EB (2 micrograms) and were REMd for 120 hours. Animals were tested daily to evaluate their LQ. EB, at this dose level, failed to elicit significant lordosis behavior in undisturbed sleep rats. REMd rats gradually increased their LQ values reaching maximal levels at 72 hours. Adrenalectomized control groups receiving the same hormonal treatment responded similarly to the experimental groups, thus discarding the participation of adrenal steroids in these effects. The present results show that REMd differentially affects the response to E and P in ovariectomized rats, enhancing the former and inhibiting the latter.     

Decreased sensitivity of Zucker obese rats to the putative satiety agent cholecystokinin

In obese rodents increased daily food intake leading to accumulation of adipose tissue is frequently accompanied by increased meal size and loss of the normal diurnal variations in feeding pattern. Increased meal size of obese rats may be due to decreased sensitivity to factors which elicit satiety. We compared Zucker obese and lean rat feeding behavior responses to octapeptide of cholecystokinin (OP-CCK), a peptide shown to decrease meal size in several species. Obese rats were less sensitive than lean rats to OP-CCK (.06, .25 and 1.0 μg/kg/meal) injected before each of four consecutive scheduled meals in the light portion of the diurnal cycle, when obese meal size was larger than lean. However, neither obese nor lean rats responded to injection of the same doses of OP-CCK during meals in the dark, when average meal size was larger than during the light and when average meal size of the obese rats was similar to that of lean rats. In both obese and lean rats injection of OP-CCK affected daily feeding pattern. Obese and lean Zucker rats are less sensitive to OP-CCK when meal size is larger, whether this is due to phase of the diurnal cycle (dark vs. light in both obese and lean rats) or phenotype (obese vs. lean rats in the light).     

Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats

Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.     

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.     

Sexual behavior of male and female septal lesioned rats

Gonadectomized male and female rats were given septal lesions (SL) or sham surgery at approximately 60 days of age. After 3 weeks lordosis behavior tests were initiated. Females were tested after daily injections of 2 μg estradiol benzoate (EB) for 3 days, while males were tested after EB only (2 μg×3 days), and after EB plus progesterone (Prog). The mean lordosis quotients (LQ) of septal lesioned female rats were significantly higher than those of sham operated controls. No increase in lordosis responding was seen in male rats with either EB alone or EB+Prog. Following an additional 3 week interval without steroid treatment masculine behavior tests began. All animals received a pretest and were tested again on Day 4, 7, 11 and 15 daily tesosterone propionate (150 μg/day) treatment. No alterations in masculine sexual behavior (relative to that of controls) were found in either male or female septal lesioned rats. It is concluded that the increased hormone sensitivity is specific for lordosis behavior, at least when the SL are given in adulthood.     

Sex behavior and the sexually dimorphic hypothalamic nucleus in male Zucker rats

To determine whether or not impaired male sex behavior in obese male Zucker rats is accompanied by any anatomical alterations in a hypothalamic area implicated in the control of sex behavior, 6 lean and 5 obese male Zucker rats were studied behaviorally and anatomically at 14 months of age. Obese males showed markedly decreased male sex behavior relative to lean males, in spite of serum levels of testosterone and testicular weights comparable to those of lean rats. Obese rats had significant decreases in brain weight and volumes of sexually dimorphic nuclei per g of brain, relative to lean rats; volumes per g brain of other structures (paraventricular and suprachiasmatic nuclei) were not different between groups. It is suggested that an incomplete expression of sexually dimorphic features of the preoptic area-anterior hypothalamus, due perhaps to an impaired process of perinatal brain androgenization, may contribute to decreased male sex behavior in adult obese rats.     

Hormonal control of the perception of the olfactory signals which facilitate lordosis behavior in the male rat

This study was designed to evaluate in the male rat the hormonal requirements for the facilitation of feminine behavior by the odor of male urine. Wistar rats from the WI and WII strains in our colony were orchidectomized (ORCH) as adults. A first group was given a single dose of 75 micrograms estradiol benzoate (EB) and tested for lordosis behavior 48 hr later. Exposure to the odor of male urine by 9 +/- 1 hr before the behavioral session did not increase the number of animals showing lordosis behavior as compared to non exposed controls. A second group of WI rats was given 0.5 micrograms EB every day for 4 to 8 days. A similar number of animals displayed lordosis behavior irrespective of whether they were exposed to the odor of urine before testing. A third group of WI rats was injected with 75 micrograms EB and 1 mg progesterone (P) 39 hr apart. Exposure to the odor of urine during estrogen treatment remained ineffective but significantly increased the number of animals showing lordosis behavior when performed at the time of P injection. A last group of WII rats was given 25 micrograms EB and 100 micrograms or 150 micrograms P 39 hr apart. Although uncapable as such to facilitate lordosis behavior the dose of 100 micrograms P rendered the animals responsive to the odor of urine. It was concluded that (1) the perception by feminized males of olfactory signals from the male was dependent on P; (2) an interaction between hormonal and sensory mechanisms was involved in the facilitation of lordosis behavior in the male rat.     

Sex differences in the basal firing rate and the responsiveness to opioid peptides of rat hippocampal neurons.

The basal firing rate and the responsiveness to dynorphin and leu-enkephalin of the neurons in the pyramidal cell layer of the hippocampus were studied in intact male, castrated male, castrated female, and castrated female rats injected s.c. with 20 micrograms estradiol benzoate (EB) for 3 days. Most of the neurons studied had low spontaneous firing rate (less than 5 Hz) and burst-like activity in all the groups. The basal firing rates in castrated males and females were not different from those in intact males and castrated females treated with EB, respectively. However, neurons in intact and castrated males had significantly higher firing rates than those in castrated females with and without EB treatment, respectively. When effective, both iontophoretically applied dynorphin and leu-enkephalin evoked predominantly excitatory responses. Either castration of males or EB treatment to castrated females did not affect the neuronal responsiveness to these peptides. On the other hand, the responsiveness of neurons to leu-enkephalin, but not to dynorphin, was significantly different between castrated male and female rats. These results suggest that sex steroids do not affect the basal firing rate as well as the responsiveness to opioid peptides of the pyramidal cells in the hippocampus in adult animals. However, sex differences in the basal firing rate and in the responsiveness to leu-enkephalin might account for the differences in hippocampal functions between male and female rats.     

Effects of corticotropin releasing factor on genetically obese (fatty) rats

Corticotropin releasing factor (CRF) has been administered into the third ventricle of lean and genetically obese Zucker fatty rats in both acute and chronic experiments. Following a single injection of CRF (5 micrograms or approximately 1 nmole) there was an acute reduction of food intake in both the lean and obese animals, but the effect was greater in the obese. This effect persisted for the first three hours but was no longer detectable in either lean or genetically obese animals at 6 hours. Binding of GDP to mitochondria from interscapular brown adipose tissue in 21-hour deprived animals was lower in the fatty rats than in the lean controls. The injection of CRF significantly increased GDP binding in both the lean and fatty rats. During chronic infusion of CRF into the third ventricle of fatty rats, there was a significant decrease in food intake in the obese rats and fall of body weight in both groups. The basal levels of GDP binding were significantly lower in the saline-infused fatty rats than in the saline-infused lean controls. The chronic infusion of CRF increased GDP binding in the fatty rats but not in the lean animals. The CRF-treated values for GDP binding in fatty rats however, remained significantly below the baseline values in the control animals. Chronic CRF infusion also significantly lowered glucose levels in the fatty rat. These studies are consistent with the hypothesis that CRF may be involved in the decreased food intake and increased sympathetic activity observed in genetically obese fatty rats following adrenalectomy.     

Metabolic responses to fasting and refeeding in lean and genetically obese rats

Injection of norepinephrine (NE) (25 micrograms/100 g body wt) caused a similar rise in metabolic rate in lean and obese (fa/fa) Zucker rats, but 3-day fasting suppressed the response in lean rats and enhanced the rise in obese mutants. Triiodothyronine (T3) injection (10 micrograms/100 g body wt) caused a significantly greater rise in oxygen consumption (Vo2) in obese than lean rats, but the response was attenuated by fasting in all animals. The thermic response to a single meal of either mixed composition, carbohydrate, or protein (40 kJ) was much smaller in obese rats than lean, but the response to the mixed nutrient meal was similar for all rats after a 3-day fast. Refeeding 3-day fasted lean rats with a single carbohydrate meal (40 kJ) caused a rise in plasma T3 levels after 3 h and a delayed increase in metabolic rate 24 h later. Injection of NE instead of refeeding caused a similar delayed rise in metabolic rate. Carbohydrate refeeding had no effect on plasma T3 levels or oxygen consumption in 3-day fasted obese Zuckers, but injection of NE did produce a significant increase in metabolic rate after 24 h. Refeeding 3-day fasted rats with protein (40 kJ) caused a rise in oxygen consumption 24 h later in lean animals but had no effect in obese animals. The data from lean Zucker rats confirm previous findings in Sprague-Dawley rats and suggest that the thermic response to refeeding involves a complex interaction between the sympathetic nervous system and thyroid hormones. Obese Zuckers responded normally to NE and T3, indicating that their reduced thermogenesis after food may be due to insensitivity to nutrient availability or an inability to activate the sympathetic nervous system.     

High dosage testosterone propionate induces copulatory behavior in the obese male Zucker rat

Genetically obese male Zucker rats sire few litters compared with lean males. High dosage testosterone propionate (TP) dramatically improves their litter production. Here we report the effect of high dosage TP on the copulatory behavior of obese males. Subjects were placed with ovariectomized, hormonally-primed females 24 hr after receiving a subcutaneous injection of vehicle or 20 mg TP. Other obese males received three consecutive daily TP injections or TP once every three days for up to 30 days prior to being tested. While 90% of sham-injected lean males became sexually active, only 18.2% of sham-injected obese males did so. In contrast 50% to 62.5% of TP-injected obese males became active depending on TP exposure. The proportion of obese males which ejaculated was high for sham-injected males which copulated, but varied with TP exposure for TP-injected males. In other respects the copulatory performance of obese and lean males was similar. High dosage TP increases fertility by correcting a behavioral deficit. Three possible mechanisms of TP action are proposed.     

Participation of the olfactory system in the control of approach behavior of the female rat to the male

The amounts of time spent by females in the sector of an open field close to the cage housing a normal male or a castrated male were measured in order to quantitate the tendency of the female to reach physical proximity to a sexually active male (androtropism). Intact proestrous or ovariectomized females primed with 100 micrograms of estradiol benzoate/kg b. wt. (EB) or EB plus 2 mg progesterone/kg b. wt. (P) spent significantly more time close to the sexually active (intact) male than in the proximity of the orchidectomized male. In order to determine whether olfactory clues were sufficient for female rats to distinguish between intact and castrated males, the males were removed from the stimulus cages, leaving the soiled bedding in place. Ovariectomized rats primed with EB or EB plus P clearly preferred proximity to the cage where the intact male had been living. No preference was evident after transection of olfactory nerves in proestrous rats or in ovariectomized rats primed with EB plus P. Resection of the vomeronasal organ also suppressed preference. These results indicate that olfactory input is necessary and sufficient for androtropism to occur, and suggest that the accessory olfactory system is involved in the analysis of olfactory signals used by female rats to identify the endocrine status of prospective sexual partners. In a different group of animals, it was demonstrated that destruction of the posteromedial cortical amygdaloid nucleus also suppressed preference for the intact male. It is proposed that this structure serves as a relay station for the analysis and integration of olfactory input significant for the motivational control of sexual behavior in the female rat.(ABSTRACT TRUNCATED AT 250 WORDS)     

Olfactory environment and early mating behavior in the cyclic female rat

The objectives of this study were to examine the effects of olfactory cues from the male and of olfactory bulb removal on early mating behavior in sexually inexperienced diestrous female rats primed with estrogen. Four-day cyclic rats isolated from the male were given either 2.5 micrograms or 10 micrograms estradiol benzoate (EB) and presented to stimulated males in the late afternoon of diestrus 2 between 18:00 and 19:00 for a 10 min sexual behavioral session. Dose-dependent effects of estrogen were observed since 10 micrograms EB significantly increased the proportion of females displaying early mating as compared with those given 2.5 micrograms EB. Olfactory bulb removal prior to estrogen treatment caused a rise in the number of females which mated early with respect to the non bulbectomized controls. Exposing the females to bedding soiled with male urine on diestrus 2 at 10:00 did not affect early mating behavior. By contrast the olfactory stimuli became efficient when 2.5 micrograms EB treated females were given 10 micrograms progesterone (P) by the time of exposure to male urine. The results were discussed with respect to the role played by the olfactory system in the control of lordosis behavior throughout estrous cycle in female rats. P was concluded to be involved in the perception of the olfactory signals from the male which facilitate early mating behavior in diestrous female rats.     

Relationship of dietary intake to the development of glomerulosclerosis in obese Zucker rats

Obese Zucker rats are hyperphagic and develop premature glomerulosclerosis. The purpose of this study was to find out the effects of restriction of dietary intake on this glomerulosclerosis. The obese and lean male Zucker rats were fed with restricted amounts of balanced diet for periods of 40 and 50 weeks, sacrificed, and the body weight, the light and ultrastructural alterations of glomeruli, and the serum levels of blood urea nitrogen, triglyceride, and cholesterol were examined. Obese and lean male rats of identical ages were fed ad libitum with the diet and studied similarly. The dietary restriction significantly lessened the development of the glomerulosclerosis in obese rats, while those on the nonrestricted diet manifested an advanced glomerulosclerosis. The dietary restriction, however, did not normalize the obesity nor correct the elevated serum lipid level to the range of lean control rats. The spontaneous glomerular lesions of the obese rats were characterized by segmental mesangial expansion, disappearance of podocytes and endothelia, and obliteration of capillary lumina. The lean rats maintained essentially normal renal morphology. A similar study on the renal morphology done in female Zucker rats also revealed a preventive effect of dietary restriction on the development of glomerulosclerosis. In conclusion, there is a strong association between the glomerulosclerosis and the hyperphagia of the obese Zucker rats, both in males and females, and the emergence of this lesion is preventable to a significant degree.