Resistance of male Sprague-Dawley rats to sucrose-induced obesity: effects of 18-methoxycoronaridine

Evidence suggests that the development of obesity in males and females might be mediated by distinct mechanisms, warranting different treatment approaches. In previous studies from this laboratory, a high sucrose diet induced excessive weight gain in female Sprague-Dawley rats and administration of a selective antagonist of α3β4 nicotinic receptors, 18-methoxycoronaridine (18-MC), prevented this form of obesity. In the present study similar parameters were studied in male rats by using an identical experimental protocol. The effects of repeated administration of 18-MC on body weight gain, deposition of fat, consummatory behavior and biochemical markers of obesity in male rats were also assessed. In contrast to females, males consuming ad libitum quantities of sucrose solution (30%) in combination with normal chow did not become obese; they did not gain excessive weight nor show excessive fat deposition. Repeated administration of 18-MC (20 mg/kg, i.p.) attenuated weight gain in both sucrose-consuming and control animals without altering food or fluid intake. The present results indicate that males and females are differentially responsive to high carbohydrate-diet obesity. Such gender disparities could be secondary to sex-specific alterations in cholinergic mechanisms of feeding and body weight regulation.     

Post weaning high fat feeding affects rats' behavior and hypothalamic pituitary adrenal axis at the onset of puberty in a sexually dimorphic manner

Feeding adult rats with high fat (HF) diets can alter their hypothalamic pituitary adrenal (HPA) axis responsiveness. In the present study, we examined the effect of a high fat diet, applied in rats from weaning to puberty, on their behavior and HPA axis status at puberty onset. Wistar rats of both sexes were fed postweaning with two diets containing either 24% fat (high fat, HF) or 4.3% fat (normal chow) by weight. HF enhanced puberty onset in female rats, without increasing body weight gain in either sex, compared with chow-fed animals. In the forced swim test, HF males exhibited a more active behavioral response on the first day, whereas HF females a more passive response during the second day of the test, as compared with their chow-fed counterparts. In the open field test, HF females showed increased sniffing but reduced rearing, compared with chow-fed females and were less explorative than HF males in the central arena. All animals could learn and recall a water maze task though HF males spent more time in the opposite quadrant than chow-fed males during memory test. The HPA axis status of these animals was investigated under basal conditions. Pubertal fat-fed males had lighter adrenals, while females heavier ones, compared with their counterparts. In addition, plasma corticosterone levels of female rats were increased and glucocorticoid receptor levels in their hypothalamus were reduced due to fat diet, while in males no such changes were detected. We conclude that HF feeding during the prepubertal period can affect behavior and the HPA axis of rats at puberty onset, well before the appearance of the obese state, in a sexually dimorphic manner. Fat diet impacted more the female HPA axis, suggesting that their system is more sensitive to fat-induced nutritional imbalance during adolescence. Present data suggest that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction that in turn may trigger the appearance of stress-related disorders during adolescence.     

Sex differences in the effects of voluntary activity on sucrose-induced obesity

Sedentary, adult rats of both sexes fed Purina chow and a 32% sucrose solution overate, gained excess weight and had higher Lee Indexes of obesity than control animals fed only Purina chow. The magnitude of these effects was similar in the males and females. Animals of both sexes fed the sucrose diet showed a slower rate of weight loss during food deprivation than the chow controls. Access to an activity wheel led to a reduction in caloric intake and the elimination of obesity in male rats. In the chow fed male rats activity led to a smaller, transient suppression in caloric intake and a slightly lower level of body weight than the sedentary chow controls. Access to activity did not affect body weight in the female rats in either dietary condition. Rather, both active groups of female rats appeared to compensate for the energy cost of voluntary activity by a small increase in food consumption. Long-term exposure to activity was associated with more rapid weight loss during food deprivation in both males and females. These data reveal that high levels of activity and obesity can co-exist when normal female rats are fed a palatable diet but that activity eliminates this form of obesity in the male rat.     

Exercise and the development and persistence of dietary obesity in male and female rats

Adult male and female hooded rats were housed in sedentary conditions or were given free access to a running wheel. Exercising and sedentary rats received either a palatable, mixed, high energy diet with chow (experimental group) or only chow (control group). Exercise reduced the weight gain of the males but not of the females. All experimental groups preferentially selected the palatable foods. Both exercising and sedentary females and the sedentary males became obese compared to their controls, but the exercising males did not. The mixed diet was withdrawn after 10 weeks: thereafter the male and female sedentary experimental groups maintained the elevated body weight. The exercising experimental females showed significant weight loss. Analysis of x-ray photographs indicated that elevated body weight in the experimental rats probably reflected increased deposition of fat and not skeletal growth. The results show that the effect of exercise on the development of dietary obesity is different in males and females, and that sedentary male and female rats can both show persistent dietary obesity after withdrawal of the palatable foods.     

Effects of wheel running on food intake and weight gain of male and female rats

Adult male and female rats were housed in a sedentary condition or given free access to a running wheel for 50 days. Running wheel activity of female rats was higher than that of males throughout the experiment. Food intake, of both male and female rats that could take exercise increased, and the rate of increase of females was greater than that of males. In both males and females there was a positive correlation between food intake and running wheel activity. These findings suggest that the sex difference in the rate of increase in food intake elicited by wheel running is at least partly explained by the sex difference in running wheel activity. Although food intake increased as a function of running wheel activity, the weight gains of both sexes were slower than those of sedentary rats. In both sexes this slower weight gain was mainly due to less accumulation of fat.     

Effect of pre- and postweaning nutrition on dietary induced obesity in B6D2F2 mice

Our purpose was to ascertain whether a phase of postnatal overfeeding would interact with preweaning litter size in influencing dietary induced obesity in mice. Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters were maintained on high fat (HF) or control diets (C) for 6 weeks, beginning at weaning. After a further 4 weeks on lab chow, all animals were fed a cafeteria diet for another 6 week period. Body weight at weaning indicated Lg less than Md and Sm animals. Lg animals gained more weight during the postweaning period but their body weight remained lower than the Sm. HF animals from all litter sizes consumed more calories and gained more weight than C animals. During the period of cafeteria feeding the Sm animals gained more weight than the Md and Lg. Although males were heavier than females, the sexes responded similarly to treatment. The postweaning dietary regimen had no effect on the weight gained in response to cafeteria feeding.     

Lack of diet-induced thermogenesis following lesions of paraventricular nucleus in rats

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.     

Developmental patterns of macronutrient intake in female and male rats from weaning to maturity

Male and female Sprague-Dawley rats had available pure macronutrient diets, protein, carbohydrate and fat, from birth to day 77 of age. Analyses of their intake of these nitrients, as a function of age, demonstrate that, in both sexes, daily protein intake and preference for this nutrient relative to the other macronutrients rise steadily from weaning and peak precisely at the time of puberty (day 37–44 for females and days 42–49 for males), when there is also a peak in body weight gain. This is in contrast to daily carbohydrate intake, which peaks 2 weeks after puberty in males, and also to the female and male rats' preference for carbohydrate, which remains relatively stable from weaning to maturity. These patterns also differ from those observed for daily fat intake and fat preference for females and males, which are relatively high during the first postweaning week and then decline and remain very low until shortly after puberty (day 54), when there occurs a sharp burst in fat intake. Comparisons between the females and males reveal a significantly stronger preference for carbohydrate in the females, exhibited as early as 23 days of age; a stronger preference for protein and fat in the males, evident after day 28; and greater light-period feeding of carbohydrate and fat by females compared to males, apparent after puberty. Correlational analyses demonstrate that body weight and total kcal intake are closely related to daily protein consumption, more strongly in females compared to males; are strongly related to daily fat intake only in males; and are unrelated to intake of carbohydrate, at any age and in either sex.     

Effects of age,sex, and prior body weight on the development of dietary obesity in adult rats

Adult male and female rats were fed either lab chow (Groups 2 and 3) or lab chow and an assortment of palatable supermarket foods (Group 1) during Days 1–60 of the experiment. All rats were maintained on only lab chow during Days 61–90. Group 1 and 3 rats were then given the supermarket diet during Days 91–150, while Group 2 rats continued on lab chow only. The rats fed the supermarket diet significantly more body weight than did the lab chow fed rats, and this dietary obesity was greater in the older rats (i.e., during the Days 91–150 of the experiment) than in the younger rats (Days 1–60). Male rats gained as much or more weight on the supermarket diet as did the females, but compared to the same-sexed chow fed rats females displayed greater weight gains than did males. Finally, during Days 91–150 Group 1 and 3 rats gained similar amounts of weight on the supermarket diet despite the fact that the Group 1 rats had previous experience with the diet and had been overweight as a result. The findings demonstrate that age and sex, but not prior experience with palatable foods and overweight, are important factors in the development of dietary obesity in adult rats. The similarity between dietary obesity and hypothalamic obesity with respect to these three factors is discussed.     

Fasting plasma triglyceride levels and fat oxidation predict dietary obesity in rats

We investigated whether fuel metabolism prior to high-fat feeding differs in outbred Sprague-Dawley rats either prone or resistant to diet-induced obesity. Chow-fed rats were deprived of food, and blood was collected 12, 18, and 24 h later. Rats were then fed a high-fat diet ad libitum for up to 4 weeks to assess weight gain. Blood samples were analyzed for a variety of metabolic fuels and hormones. Only fasting plasma triglyceride concentrations showed a positive correlation with the weight gain during the high-fat feeding period, with concentrations after 18 h of fasting showing the most consistent relationship to weight gain. Body weights and fat pad weights did not correlate with fasting plasma triglyceride concentrations before high-fat feeding. The amount of 14CO(2) recovered from gavaged [14C]palmitic acid in chow-fed rats negatively correlated with weight gain during the subsequent period of high-fat feeding. These results show that there are preexisting differences in fat catabolism that may underlie differential susceptibility to diet-induced obesity; in particular, fasting levels of plasma triglycerides and fatty acid oxidation may be early predictive markers for this susceptibility.     

Consumption of a high-fat diet alters the homeostatic regulation of energy balance

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.     

Age, sex and reproductive status alter the severity of anorexia in zinc deficient rats

Food intake and body weight gain in rats fed a zinc-deficient diet are reported. The severity of zinc deficiency-induced anorexia was observed to be dependent upon the age, sex and reproductive status of the animal. Rapidly growing rats such as weanlings, adult males, or ovariectomized females demonstrated more rapid induction of anorexia and more severe effects on cumulative food intake and body weight gain when fed zinc-deficient diets than did slowly growing (nonpregnant female adult) rats given the same diet. These results suggest that feeding in zinc-deficient animals is not regulated by dietary zinc concentration alone, but rather is mediated by one or several as yet undefined factors.     

Protein and energy relations in the broiler. 3. Growth and in vitro lipid metabolism in male and female chickens used as parent stock

Growth and in vitro metabolism were assessed in 4 wk-old Ross male and Vedette dwarf female chickens and the offspring of this mating. Chicks were fed diets formulated to contain the same carbohydrate energy level (56% of total metabolizable energy) but different levels of protein (12, 18, 23 and 30%) for 21 days beginning when they were 7 days of age. Dietary regimes were devised to study the role of protein per se in the regulation of growth and in vitro lipogenesis. Dietary protein had little effect on dwarf female growth. Males receiving the diet containing 30% protein and fed ad libitum grew at a slower (P less than .05) rate than did males receiving the 18 or 23% protein diets. A 3-day rotational feeding regime that consisted of three different levels of dietary protein (12, 23 and 30%) did not adversely affect the growth of either males or females when compared to the effect of feeding a 23% protein diet ad libitum. Intermittent feeding decreased (P less than .05) feed consumption and weight gain of both sexes. In vitro hepatic lipogenesis in both males and females was inversely related to the level of protein in the diet being fed; however, the overall lipogenic rate for males was greater (P less than .05) than that for females. Certain liver enzyme activities were also inversely related to the level of dietary protein and the analysis of data suggested that both reducing equivalent (NADPH) production and the malate-alpha ketoglutorate shuttle were also related to dietary protein status.     

Brown adipose tissue thermogenesis and metabolic rate contribute to the variation in obesity among rats fed a high fat diet.

A high fat (HF) diet is known to induce obesity, but susceptibility to obesity induced by a HF diet differs not only among different strains of rats but also within the same strain. The present study revealed that the Lee index (an index of obesity) positively correlated with insulin, and inversely correlated with both the mitochondrial oxygen consumption in interscapular brown adipose tissue (BAT) and the resting metabolic rate (RMR) in Sprague-Dawley rats. This suggests the contribution of BAT thermogenesis and RMR, in addition to hyperphagia, to the intrastrain variation in susceptibility to HF diet-induced obesity.     

18-Methoxycoronaridine blocks acquisition but enhances reinstatement of a cocaine place preference

The iboga alkaloid congener, 18-methoxycoronaridine (18-MC), decreases self-administration of multiple drugs of abuse. Here, in a biased procedure, we investigated whether 18-MC would have a similar effect on the acquisition, expression and reinstatement of a cocaine conditioned place preference (CPP) in male Sprague-Dawley rats. While 18-MC attenuated acquisition of a cocaine CPP, it had no effect on CPP expression, and enhanced the reinstatement of cocaine CPP following extinction. Our results are consistent with those obtained using ibogaine, but reinforce the notion that acquisition, expression and reinstatement of a CPP likely involve separate mechanisms.     

Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat–high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon-like peptide (GLP-1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down-regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein-3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin-6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.     

High fat/sucrose feeding attenuates the hypertension of spontaneously hypertensive rats

To assess the caloric and cardiovascular effects of dietary obesity on an important animal model of hypertension research, 60-day-old male spontaneously hypertensive (SHR) rats were fed either Agway pelleted chow (Pellet), a diet enriched in fat and sucrose (HF/M), or alternated (Cycled) between 2-week periods of HF/M diet and Agway pelleted chow. After 14 weeks, HF/M feeding elevated the body weight of SHR rats by 15% over the body weight of pellet-fed control rats. This relative obesity was accompanied by heavier white (retroperitoneal) and brown (interscapular) fat pads, heavier heart weights, and tachycardia. Paradoxically, the systolic blood pressure levels of SHR rats fed the HF/M diet were reduced. Ruled out as an explanation for the blood pressure reduction was the relative polyunsaturated to saturated fat (P/S) rati of the diet. The hypertension of SHR rats may be due in part to the effects of an underlying metabolic problem that is counteracted by the effects of HF/M feeding; HF/M feeding not only elevated body weight but also reversed the hypoinsulinemia found in pellet-fed SHR rats. The Cycled group evidenced large up-and-down swings in caloric intake that coincided with HF/M and Pellet feeding; this produced modest staircase-like changes in body weight gain. Similar to the HF/M group, the systolic blood pressure level of the Cycled group was also reduced in comparison to the blood pressure level of the Pellet group. However, the Cycled group was found to be more responsive to the pressor effects of intravenous phenylephrine, an alpha-adrenergic agonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feeding with powdered diet after weaning affects sex difference in acetylcholine release in the hippocampus in rats

We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9-12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals under freely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet.     

Sexual dimorphism in the adrenergic control of rat brown adipose tissue response to overfeeding

Gender-related differences in the brown adipose tissue (BAT) response to overfeeding rats on a cafeteria diet were studied by assessing the balance between the expression of beta-adrenoceptors (beta1-, beta2-, beta3-AR) and alpha2A-AR and their relation to the expression of uncoupling proteins (UCP1, UCP2, UCP3). Cafeteria diet feeding for 15 days, which involved a similar degree of hyperphagia in both sexes, led to a greater body weight excess in females than in males and a lower activation of thermogenesis. Gender-related differences were found for different adrenoceptor expression and protein levels, which might explain, in part, sex differences in the thermogenic parameters. The lower expression of alpha2A-AR in females than in males could be responsible for the higher expression of UCP1 and thermogenic capacity under non-hyperphagic conditions. However, in a situation of high adrenergic stimulation--as occurs with overfeeding--as there is a preferential recruitment of the beta3-AR by noradrenaline compared with other adrenergic receptors, the higher levels of beta3-AR in males rats than in females could be responsible for the greater thermogenic capacity and the lesser weight gain in males. Thus, the alpha2/beta3 balance in BAT could be a key in the thermogenic control.     

Longitudinal study of solute excretion and glomerular ultrastructure in an experimental model of aging rats free of kidney disease

Because experimental studies of kidney aging are frequently complicated by the presence of renal disease, we set out to define a model minimizing renal pathology and thus revealing basic aging phenomena. Male and female Wistar/Lou rats were conceived, born, and bred to 42 months in a specific pathogen-free husbandry. They had free access to water and to a protein diet containing 2% fish and 15% vegetable proteins. The mean survival ages of this colony were 39 months for females and 35 months for males. Body weight, 24-hour food and water intake, urinary volume, and solute excretion were measured every 6 months in a group of 12 males and 12 females. Throughout the study, the mean body weight remained close to 180 gm in females and 320 gm in males. Despite this size difference, absolute daily food intake was similar in the two sexes and almost constant over the studied period. Age-related changes in proteinuria and phosphate excretion were greater in males than in females. Decreased urine osmolality and increased urinary volume, on the other hand, were more pronounced in old females than in males. Renal loss of calcium was noticed in both sexes and glucosuria remained discrete. Kidneys examined at 12, 24, and 36 months in both sexes and also at 42 months in females were free of major pathology such as pronounced glomerulosclerosis, tubular nephrosis, tubular cast, or hydronephrosis. In the oldest animals a few foci of interstitial inflammation occasionally were seen. The sole significant morphologic change was a regular but moderate thickening of the glomerular basement membrane, which roughly doubled its size from 12 to 36 months. Morphometric studies failed to demonstrate an increase in mesangial matrix or mesangial cellularity. No changes in foot processes, slit diaphragms, or endothelial fenestrae were seen with increasing age. These observations indicate that basic age-related changes in kidney structure and function of rats fed ad libitum can be reduced to a few parameters provided that adequate strains, diet, and husbandry conditions are selected for experimentation.