Perinatal dietary NaCl level: effect on angiotensin-induced thermal and dipsogenic responses in adult rats

We have shown previously that administration of angiotensin II (Ang II) produces an apparent decrease in thermoregulatory set point. Exposure to high salt diets either perinatally or later in life has been shown to increase pressor responsiveness to administration of Ang II, so in the present studies we examine whether high dietary NaCl would also increase the thermal responsiveness to Ang II. In the first study, we show that exposure to a basal NaCl diet (0.12%) during gestation through 4 weeks postnatally produced very large elevations in plasma renin activity (PRA) and aldosterone concentrations in the offspring. Exposure to high salt diet (3%) did not decrease the levels of these parameters below those fed mid salt diet (1%). In the second study, we show that rats raised through 4 weeks of age on basal diet, but then fed standard chow until adulthood, showed greater changes in tail skin (T(sk)) and colonic (T(c)) temperatures following administration of Ang II (200 microg/kg sc) than either mid- or high-salt-raised groups. In the third study, we confirmed this finding and extended it to show that rats raised on a very high salt diet (6%) also did not differ from the mid-salt group. In both studies, acute water intake measured in a separate test following administration of Ang II did not differ as a function of perinatal salt diet. In a fourth study, the period of exposure to the diets was extended from the perinatal period through adulthood and, surprisingly, there was no longer an enhanced thermal response to Ang II in basal diet rats compared with rats fed the very high salt diet. In the final study, rats raised on a regular diet but exposed only as adults to the test diets showed a nonsignificant trend toward a decreased thermal response in the basal group. Thus, dietary salt level may have opposite effects on Ang II effects on adult thermoregulation, depending on the age at the exposure.     

Leptin resistance in mice is determined by gender and duration of exposure to high-fat diet

Mice fed a high-fat diet are reported to be resistant to peripheral injections of leptin. We previously failed to induce leptin resistance in female mice fed a high-fat diet for 15 weeks. Therefore, we measured the responsiveness to peripheral infusions (10 microg/day) of leptin, and the responsiveness to third ventricle injections of leptin (1 microg) in male and female NIH Swiss mice fed low-fat (10% kcal) or high-fat (45% kcal) diets. Male and female 15-week-old mice that had been fed low- or high-fat diet from 10 days of age lost fat during a 13-day intraperitoneal infusion of leptin and lost weight in response to a single central injection of leptin. Fifteen-week-old male mice fed a high-fat diet for 5 weeks did not lose body fat during a peripheral infusion of leptin and did not lose weight in response to a central injection of leptin. Female mice fed high-fat diet for 5 weeks remained leptin-responsive. Weight loss was achieved without a significant voluntary decrease in food intake, suggesting that both peripherally and centrally administered leptin increases energy expenditure. These results demonstrate that the development of leptin resistance in NIH Swiss mice fed a high-fat diet is dependent upon the gender of the mice and either the duration of exposure to high-fat diet or the age at which the mice are first exposed to the diet.     

Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area

Voluntary wheel running (WR) is a form of physical activity in rodents that influences ingestive behavior. This study examined the effects of WR on dietary preference and the potential role of leptin in mediating these effects. In a two-diet choice paradigm in which both palatable high-fat (HF) food and standard laboratory chow were provided ad libitum, rats displayed a strong preference for the former and chose to eat almost exclusively the HF diet over chow in sedentary conditions. With free access to running wheels, however, rats exhibited no preference for the HF food and consumed equal gram amounts of both chow and HF diets. The total daily caloric consumption during WR in the dietary choice protocol was equivalent to the amount of calories consumed daily by WR rats with only chow or only HF diet available, yet significantly less than sedentary chow caloric consumption. Two days after initiating WR, leptin signal transduction was examined in multiple selected brain sites following leptin injection into the third cerebral ventricle. The maximal leptin-stimulated STAT3 phosphorylation was enhanced only in the ventral tegmental area (VTA), but not in the arcuate nucleus, lateral hypothalamus, dorsal medial or ventral medial hypothalamus, or substantia nigra. In conclusion, wheel running appears to act either as an independent reinforcing factor or as a more favored activity to substitute for the consumption of a palatable HF diet, thus eliminating the preference for the HF food. Moreover, WR enhances leptin signaling specifically in the VTA, suggestive of a WR-evoked mechanism of heightened leptin function in the VTA to curb the drive to consume palatable HF foods.     

Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na⁺,K⁺-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na⁺,K⁺-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na⁺,K⁺-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.     

Sex difference in blood pressure of spontaneously hypertensive rats influenced by perinatal NaCl exposure.

Our prior study showed that the basal blood pressure level and pressor response to peripheral angiotensin II of adult Sprague-Dawley rats were enhanced by perinatal exposure to a high NaCl diet. The purpose of the present study was to assess further the relationship between NaCl-sensitivity of blood pressure and perinatal NaCl exposure. We tested the hypothesis that the basal blood pressure level and pressor responses to angiotensin II could be increased by perinatal exposure to high NaCl in NaCl-resistant spontaneously hypertensive rats (SHR-R). Adult female SHR-R were maintained on a diet containing either basal 1% or high 8% NaCl throughout pregnancy and lactation. The offspring were continued on these same diets to 30 days postpartum. Thereafter, all offspring were maintained on a diet containing 1% NaCl. After being adapted to restraint, systolic blood pressure was measured indirectly by the tail-cuff procedure when the rats were 30, 44, and 58 days of age. Subsequently, baseline mean arterial pressure (MAP) and pressor responses to intravenous administration of angiotensin II (20, 40, 80, and 120 ng/kg body weight) were obtained from the catheterized femoral artery in conscious unrestrained rats. The MAP levels of adult female SHR-R exposed perinatally to 8% NaCl were significantly greater than those of females exposed to 1% NaCl. This elevated blood pressure was accompanied by an elevation in plasma osmolality. Perinatal exposure to 8% NaCl did not raise the blood pressure and plasma osmolality levels of adult male SHR-R, but did enhance pressor responses to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet

Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n=24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n=12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch-Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf-Ch). Caf-Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf-Caf). Caf-Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch-Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf-Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch-Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.     

Dietary hyperphagia in rats: role of fat, carbohydrate, and energy content

Dietary energy, fat and carbohydrate content were varied to determine the nutritional factors responsible for hyperphagia induced by feeding rats high-fat diets. In the first experiment, rats were fed isoenergetic high-fat or high-carbohydrate diets for 2 weeks. Weight gain and energy intake were lower in rats given the high-fat diet. When some of the rats were switched to a diet that was high in fat, carbohydrate and energy, gram food intake was initially unchanged, resulting in a substantial increase in energy intake and weight gain. Energy intake gradually declined over the 4 weeks following the switch to the high-energy diet. In the second experiment, rats were fed high-fat diets that were either high or low in carbohydrate content and either high or low in energy content (kcal/g). Rats fed a high-fat diet that was high in energy and carbohydrate ate the most energy and gained the most body weight and carcass fat. In the third experiment, rats were fed high-carbohydrate diets varying in fat and cellulose content. Energy intake and body weight gain varied directly as a function of caloric density regardless of the fat or cellulose content of the diets. It is concluded that hyperphagia induced by feeding high-fat diets is not due to the high dietary fat content alone. Rather, high levels of fat, carbohydrate, and energy interact to produce overeating and obesity in rats fed high-fat diets.     

Perinatal exposure to a high NaCl diet increases the NaCl intake of adult rats

To determine the effect of differences in perinatal NaCl exposure on NaCl intake, adult Sprague-Dawley female rats were maintained on diets containing either 0.12, 1.0, or 3% NaCl throughout pregnancy and lactation. The offspring were continued on the these same diets to 30 days postpartum. Thereafter, all offspring were fed the same basal diet containing 1% NaCl. At 90 days of age, the adult offspring were placed in metabolism cages for 7 days and fed 1% NaCl chow for days 1-2, and 0% NaCl chow for days 3-7. On days 6-7, the animals were free to consume both water and 0.3 M NaCl. When dietary NaCl was available, adult rats exposed perinatally to the high NaCl diet excreted significantly more sodium on days 1-2 and 6-7 than did the rats exposed to either the mid or low NaCl diets. There were no differences in sodium excretion during sodium deprivation on days 3-5. The 0.3 M NaCl intake of the high NaCl-exposed rats was also significantly greater than the intake of the mid and low NaCl-exposed rats. In another group of adult rats, exposed perinatally to either a low or high NaCl diet, the spontaneous 24-hr intake of water and 0.3 M NaCl was measured after repeated episodes of acute sodium depletion. Sodium depletion was induced by 48 hr of dietary sodium deprivation combined with a single subcutaneous injection of 5 mg furosemide. Acute sodium depletion was found to augment existing differences in NaCl intake between low and high NaCl-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同脂肪含量的高脂纯化配方饲料对大、小鼠代谢综合征发生的影响

 摘要： 目的 探讨不同脂肪含量的高脂纯化配方饲料对大、小鼠体重、血糖、血胰岛素、血脂、脂肪肝及白蛋白尿的影响。 方法 雄性SD大鼠及C57BL/6小鼠随机分为MS10%、MS45%和MS60%脂肪含量饲料组,喂养3个月,检测动物体重、血糖、血胰岛素水平、血脂和蛋白尿水平,以及主要脏器重量及肝脏脂质含量。 结果 与正常组（MS10%脂肪含量）相比,高脂组（MS45%和MS60%脂肪含量）动物体重显著增加,出现明显的糖耐量异常、胰岛素抵抗和血脂水平升高,同时伴有肝脏脂质含量和蛋白尿水平的增加,并且以MS45%高脂组体重增加及胰岛素抵抗更加显著。 结论 MS45%和MS60%高脂配方饲料均可在大、小鼠较好地诱导代谢综合征的发生,而且前者优于后者。 关键词： 高脂饲料;胰岛素抵抗;肥胖;代谢综合征     

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 diet preference in developing and adult rats

Diet preference tests in rats have yielded equivocal results, as some investigators have reported a strong preference for diets high in fat over those containing less fat, while others have failed to see this preference. To further explore this unresolved problem, two diet preference experiments were conducted. In Experiment 1, adult rats were maintained for at least three months on one of three powdered diets (control, high-carbohydrate or high-fat). Rats were then given a preference test with all three diets available. Animals from each group overwhelmingly preferred the high-fat diet. To determine whether this preference was also present in younger, developing rats, in Experiment 2, weanling animals were tested with the same three diets as in Experiment 1. As observed with adult animals, weanling rats also showed a strong preference for the high-fat diet. The idea that rats prefer a diet with a relatively high level of fat is supported. Possible explanations for these findings are discussed.     

Neurological and stress related effects of shifting obese rats from a palatable diet to chow and lean rats from chow to a palatable diet

Rats exposed to an energy rich, cafeteria diet overeat and become obese. The present experiment examined the neural and behavioural effects of shifting obese rats from this diet to chow and lean rats from chow to the cafeteria diet. Two groups of male Sprague Dawley rats (n = 24) were fed either highly palatable cafeteria diet or regular chow (30% vs. 12% energy as fat) for 16 weeks. Half of each group (n = 12) was then switched to the opposing diet while the remainder continued on their original diet. The effects of diet switch on the response to restraint stress were assessed and rats were euthanised nine days after diet reversal. After 16 weeks of cafeteria diet, rats were 27% heavier than controls. Rats switched from chow to cafeteria diet (Ch–Caf) became hyperphagic and had increased dopamine D1, D2 and tyrosine hydroxylase mRNA expression in the ventral tegmental area (VTA) compared to rats switched from cafeteria to chow (Caf–Ch). Caf–Ch rats were hypophagic with significant reductions in white (16%) and brown (32%) adipose tissue mass, plasma leptin (34%) and fasting glucose (22%) compared to rats remaining on the cafeteria diet (Caf–Caf). Caf–Caf rats had an elevated plasma corticosterone response to restraint stress compared to Ch–Caf rats indicating that acute but not chronic consumption of palatable cafeteria diet may protect against stress. Caf–Ch rats had increased corticotropin releasing hormone mRNA expression in the dorsal hypothalamus compared to Ch–Ch rats implying that removal of the palatable diet activated the HPA axis. The results were discussed in terms of the links between palatability of diet, obesity and stress.     

Liver of ovariectomized rats is resistant to resorption of lipids

Ovarian hormones have been shown to regulate liver lipid accumulation in rats. The present study was designed to evaluate liver lipid resorption in ovariectomized (Ovx) rats. Ovx and sham-operated (Sham) rats were submitted to a high-fat (HF; 43% kcal fat as energy) diet for 5 weeks and then either maintained on this diet or switched to a standard (SD; 12.5% kcal fat as energy) diet till weeks 8 and 13 (n=8 rats/group). Body weight, energy intake, liver and intra-abdominal fat accumulation and plasma metabolic profile were determined. Body weight was significantly (P<0.01) higher in Ovx than in Sham groups at all times and switching diet did not alter the body weight pattern. The weight of the intra-abdominal fat depots and plasma leptin levels, along with liver triacylglycerol (TAG) concentrations, were significantly higher (P<0.01) in Ovx than in Sham rats. Switching diet reduced intra-abdominal fat depot weight and plasma leptin in all groups. Switching diet also resulted in a decrease in liver fat accumulation in Sham rats at all times. However, 8 weeks after the diet switch (week 13) liver fat accumulation was as high in Ovx rats as those maintained on the HF diet. When liver TAG values measured at week 13 were compared to initial pre-switching values (week 5), liver TAG levels in Ovx animals were maintained at the same level independently of the diet switch, while in Sham rats switching to a SD diet reduced liver TAG accumulation (P<0.05). The same comparisons with plasma TAG levels revealed an opposite relationship. These data suggest that liver lipid resorption in Ovx animals is more related to the ovarian hormone status than to the type of ingested diet.     

Diet selection and metabolic fuels in three models of diabetes mellitus

Dietary self-selection and circulating metabolic fuels (glucose, free fatty acids, ketones) were examined in three forms of experimental diabetes mellitus in rats: pancreatectomy and streptozotocin treatment in adult and neonatal rats. Changes in diet selection resulting from insulin replacement also were examined. Differences were found in diet selection and circulating metabolic fuels between these types of diabetes. Mildly diabetic rats selected large amounts of fat while more severely diabetic rats primarily selected protein. Insulin treatment enhanced carbohydrate intake of diabetic rats and nearly normalized diet selection and circulating metabolic fuels. All diabetic groups exhibited severe glucose intolerance. These results support the observations of the beneficial effects of low-carbohydrate diets, question the generality of the use of high-fat diets, and suggest a more important role for high-protein diets in energy regulation in severely diabetic rats.     

Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho–dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, ΔFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.     

Effects of abuse pattern of gestational toluene exposure on metabolism, feeding and body composition

AIMS: Inhalant abuse during pregnancy lowers birth weight and impedes early development. These studies explored the effects of brief, repeated, prenatal toluene exposures in pregnant female rats on body weight, metabolic rate, body composition, and food intake in their offspring. METHOD: Rats were exposed to 0, 8000, 12,000, or 16,000 ppm of toluene twice daily for 15 min from gestational days 8 to 20. The effects of such exposures on post-weaning litter weights, oxygen consumption, carbon dioxide output, and body fat content were determined in 2 cohorts (n=23, n=24) of offspring. Food intakes and weight changes in response to 3 different diets (regular chow, purified diet, purified high fat diet) were examined in another cohort (n=24) from postnatal days 72 to 116. RESULTS: Litter weights showed a significant linear decrease as a function of toluene dose. Offspring exposed to the 16,000 ppm toluene dose displayed statistically lower energy expenditures than control rats. Male rats exposed to 8000 or 16,000 ppm toluene had significantly greater percentage of body fat as well as total body fat than the other groups. Toluene also significantly suppressed weight gain over the time chow was consumed compared to the 0 ppm control group. Finally there were trends for a main effect of toluene dose on food intake during chow and during high fat diet consumption, with rats in the 12,000 ppm group consuming more than the 0 ppm group on both diets. DISCUSSION: These data suggest that, in addition to other previously documented abnormalities in neurological development and behavior, the physiological regulation of metabolism and body composition in males as well as food intake and weight gain in both sexes may be altered by prenatal exposure to toluene.     

Dietary fish oil does not protect rats exposed to restraint or sleep deprivation stress

It has been suggested that fish oil (FO) prevents weight loss caused by physiological stress such as cancer, injury, or cardiovascular disorders. Previously, we observed that a high-fat diet containing corn and coconut oil exaggerated weight loss caused by the mixed physiological and psychological stress of repeated restraint (RR). This experiment tested the effects of a high-fat diet containing FO as the predominant lipid source in rats exposed to the mixed physiological and psychological stress of either RR or sleep deprivation (SD). FO did not prevent stress-induced hypophagia or weight loss in RR or SD rats but exaggerated the negative effects of stress on body weight in SD rats by promoting loss of lean body mass. RR caused a reduction in body fat content irrespective of dietary treatment. In SD rats, both stress and FO independently reduced body fat mass. FO did not have any effect on adrenal and thymus weights during RR or SD and did not influence corticosterone levels after 1 h of RR or after 48 or 96 h of SD. In conclusion, our results suggest that high levels of dietary FO do not improve the response to stress in rats exposed to mixed stressors.     

Comparison of hydrogenated vegetable shortening and nutritionally complete high-fat diet on limited access-binge behavior in rats

Previous studies have suggested that intermittent exposure to hydrogenated vegetable shortening yields a binge/compensate pattern of feeding in rats. The present study was designed to assess whether rats would exhibit similar patterns of intake when given intermittent access to a nutritionally complete high-fat diet. Four groups of rats received varying exposure to either hydrogenated vegetable shortening or high-fat diet for 8 consecutive weeks. Animals were given daily and intermittent access to determine if the binge/compensate pattern of feeding was frequency dependent. At the conclusion of the study, body composition and plasma leptin levels were assessed to determine effects of diet and binge/compensate intake on endocrine alterations. As predicted, animals receiving intermittent access to high-fat diet displayed the binge/compensate pattern of feeding and appeared to compensate as a result of the caloric overload accompanying a particular binge episode. In addition, exposure to either shortening or high-fat diet led to alterations in body composition, while only exposure to shortening altered plasma leptin levels. These results suggest that binge-intake behavior occurs on a nutritionally complete high-fat diet and that this regimen is capable of altering both body composition and endocrine profile.     

Model for predicting and phenotyping at normal weight the long-term propensity for obesity in Sprague-Dawley rats

Tests were conducted to determine whether weight gain or nutrient intake measures during the first week of exposure to a macronutrient diet can accurately predict an animal's long-term propensity towards obesity. In multiple groups of normal-weight Sprague-Dawley rats (n=35-70/group), daily weight gain during the first 5 days on a high-fat diet (45-60% fat) was found to be strongly, positively correlated (r=+0.71 to r=+0.82) with accumulated body fat in 4 dissected depots after 4-6 weeks on the diet. This measure consistently identified obesity-prone (OP) rats which, relative to the obesity-resistant (OR) rats, were only slightly heavier (+15 g, 4%) and hyperphagic (+9 kcal, 8%) after 5 days but markedly heavier (+70g) with up to 2-fold greater fat mass after several weeks on the diet. Other dietary conditions and measures revealed weaker relationships to ultimate body fat accrual. The OP rats identified by their 5-day weight-gain score exhibited at this early stage clear disturbances characteristic of markedly obese rats. These included elevated leptin, insulin, triglycerides and glucose, along with increased lipoprotein lipase activity (LPL) in adipose tissue and galanin expression in the paraventricular nucleus. Most notable were significant reductions in muscle of LPL activity and ratio of beta-hydroxyacyl-CoA dehydrogenase to citrate synthase activity, indicating a decline in lipid transport and capacity of muscle to metabolize lipids. By occurring early with initial weight gain, these hypothalamic and metabolic disturbances in OP rats, favoring fat storage in adipose tissue over fat oxidation in muscle, may have causal relationships to long-term accumulation of body fat.