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This study was designed to investigate the effects of high and low n-3 FA feeding during perinatal period on the growth and FA profiles in the Wistar rat offspring. Female rats were randomized into three diet groups during pregnancy and lactation (L): Control (CON, ratio of n-3/n-6 approximately 0.14, n=24); n-3 FA deficient (LOW, ratio of n-3/n-6 approximately 0, n=31) and n-3 FA excess (HIGH, ratio of n-3/n-6 approximately 14.0, n=23). Milk samples were obtained on L14. After L24, all offspring were fed the control diet until killed at 23-25 weeks of age. There were no group differences in maternal weight gains or offspring birth weights. After birth, the HIGH offspring weighed the least while CON offspring the most. The FA profiles of the CON and LOW milk resembled CON diet, and the HIGH milk resembled HIGH diet. Body FA profiles of males from all groups were similar to the CON milk profile, but the CON and LOW females resembled the CON milk, while the HIGH females resembled the HIGH milk. All HIGH offspring had increased n-3 levels and n-3/n-6 ratios (males: 0.16+/-0.01; females: 0.23+/-0.06). Thus LOW dams likely had maternal body fat mobilization that compensated for the deficiency in dietary n-3 FA, while a compensatory mechanism was not observed when intake was high. Excess amount of n-3 FA affected female offspring more than males. These data indicate the long-lasting effects of supplementation and supplementing high amounts of n-3 FA during pregnancy and lactation may not be advisable.

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.

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.

This study was designed to test the hypothesis that short-term leptin infusion during the post-obese refeeding phase of weight-reduced rats would reduce the rate of weight regain and, as a result, reduce the final body weight and fat content in weight-reduced rats. Ninety-six female Wistar rats were divided into four groups: (1) LFCON (low-fat control) group: Rats in this group were fed the control low-fat (LF) diet ad lib for the entire study period. (2) HFCON (high-fat control) group: Rats in this group were fed the high-fat (HF, 40% fat) diet ad lib for the study period. (3) HFRLP (high-fat fed, weight-reduced, leptin treatment) group: Obese rats in this group were weight-reduced and received leptin infusion for 2 weeks (miniosmotic pumps, 0.5 microg/kg/day) during the post-obese refeeding period. (4) HFRSM (high-fat fed, weight-reduced, sham control) group: Rats in this sham-control group were treated the same as the rats in the HFRLP group with the exception that no leptin was actually infused during the first 2 weeks of refeeding period. The results demonstrated that 2 weeks of leptin treatment during the early refeeding phase did not prevent weight regain in weight-reduced rats, but it significantly reduced body fat content in these rats as compared to ad lib fed obese control rats. One cycle of weight reduction and regain did not alter the body weight and body fat content in HFRSM rats when compared to obese control rats. Therefore, leptin treatment was effective in reducing body fat content in post-obese rats for up to 7 weeks, but the long-term effect of short-term leptin treatment needs to be further examined.

To determine how chronic alcohol administration during lactation affects milk composition and the nutritional status of the dam, EtOH (3 g/kg) as a 20% solution was administered by intubation to Sprague-Dawley rats from days 2 through 15 of lactation. Control dams were pair fed to account for the reduction in food intake observed in the alcohol group, while another control group maintained ad lib food intake. Dams and their litters were weighed daily throughout the study. On day 16, dams were sacrificed and samples taken for further analysis. Blood alcohol levels as well as serum levels of calcium, cholesterol, glucose, iron, lipids, phosphorous, and triglycerides were measured. Liver lipid levels and the total composition and fatty acid profile of the phospholipids in milk were also measured. Results indicate that EtOH administration and pair feeding reduced dam body weight, but not litter growth. Serum iron levels was increased in both EtOH-exposed and pair-fed controls, whereas serum cholesterol was elevated only in EtOH-exposed dams. Finally, of the phospholipids in milk, only one, phosphatidylserine, was slightly but significantly increased by EtOH. If and how these changes impact the development of the offspring remain to be studied.

Obesity is associated with an increase in plasma leptin levels primarily derived from enhanced expression of the leptin gene in the adipose tissue. Leptin levels and expression are higher in females than males. The main functions of leptin are to decrease food intake and increase sympathetic nerve activity, especially in the brown adipose tissue. The high levels of leptin in obese, female rats suggest leptin resistance. In this article we describe experiments designed to investigate the effect of the intracerebroventricular (i.c.v.) administration of leptin on lumbar sympathetic nerve activity (LSNA) and cardiovascular parameters in female rats fed a low fat diet (control), a high fat diet (obese), or high fat diet followed by a period of food restrictions (reduced). The i.c.v. leptin administration increased LSNA in control rats, but decreased it in obese rats. In weight reduced animals the LSNA response to leptin returned to control levels. The i.c.v. leptin increased the mean arterial pressure in control and wt. reduced rats, but not in obese animals. The heart rate did not respond to leptin in any animal group. These results suggest that obesity decreases the central nervous system (CNS)-mediated lumbar sympathetic nervous and cardiovascular responses to leptin and that these responses recover following food restriction and wt. reduction. We conclude that obesity is associated with a decreased CNS response to leptin leading to a decrease in leptin effects to increase the activities of the autonomic nervous and cardiovascular systems.

We investigated if there were gender differences in metabolic consequences produced by meal feeding of a high-fat (HF) diet in male and female Osborne-Mendel rats. An HF diet was fed either ad lib (AL) or in 1 meal (MF) during the last 3 h of the dark cycle for 4 weeks (lights off from 2400 h to 1200 h). All rats were sacrificed at 1 of 3 time-points: prior to MF rats receiving their food at 0900 h, after food was taken from MF groups at 1200 h or 1500 h. Food intake, body weight, body fat weight, retroperitoneal adipose tissue lipoprotein lipase activity, plasma cholesterol, or HDL-cholesterol levels did not differ between MF- and AL-fed groups, but were higher in male than in female rats. There were no differences between the male and female groups in plasma levels of insulin and glucose or systolic blood pressures. Plasma triglyceride levels at 1200 h were significantly different between MF and AL Groups within either gender, but this was not observed at 0900 h or 1500 h. Body weights were correlated with internal fat weights and plasma cholesterol levels in both males (r = 0.57, p < 0.05) and females (r = 0.59, p < 0.05). Hence, it is the amount of HF diet ingested, rather than the pattern of meal feeding, that was the most significant factor related to gender differences in weight gain, increases in fat mass, and metabolic differences.

This study was designed to examine the interaction of pregnancy and dietary fat on pregnancy outcome and offspring metabolism in rats. Wistar rats were divided into four groups: HF (40% fat by weight) feeding and pregnant (HFP, n = 15); HF nonpregnant control (HFNP, n = 10); control diet (4.5% fat) and pregnant (CHP, n = 12); and control diet nonpregnant (CHNP, n = 10). Rats were fed the same diets throughout gestation and lactation and were sacrificed at weaning. Litter size was kept at six pups with extra pups killed at birth. HF-fed dams had significantly less caloric intake than control counterparts. HFP had similar body weight changes as CHP during gestation and lactation, whereas HFNP had significantly higher weight and fat content than CHNP. There was no difference in pup's birth weight. However, significantly more HF dams cannibalized their pups. Newborns delivered to HF-fed dams had higher insulin/glucose ratios than CH pups. HFP weanlings weighed more, had more body fat (%), higher liver weight, liver lipid content, and higher blood glucose and triglyceride levels than CHP weanlings. The long-term effects of these metabolic abnormalities need to be further examined.

Since most of the weight-reduced obese humans are in a protein deficit state, this study was designed to examine whether a high protein diet (HP) enhances the restoration of lean body mass and facilitates the maintenance of weight loss. Obesity in rats was produced by 16 weeks of high fat diet (HF) feeding. In the 17th week, all HF-fed obese rats were fed a limited amount of control diet to normalize their body weights, but they still had more body fat content. The HF-fed rats were then divided into subgroups with different diets offered for 5 weeks: HP, HF or chow diet. A control group was fed the chow diet throughout the study. HP feeding maintained normal body weight and carcass composition in weight-reduced obese rats by reducing feeding efficiency levels to within normal ranges. Weight-reduced rats fed a chow diet, however, had more fat mass than controls and HF feeding stimulated weight gain again. Therefore, a HP diet has a higher probability of enhancing weight loss maintenance in weight-reduced obese subjects than does a usual well-balanced diet.

The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.

In order to investigate the effects of the induction and remission of obesity on feeding behavior, male rhesus monkeys were made obese by sustained intragastric (IG) feeding of a complete liquid diet. Intragastric diet infusion levels of 100, 125, 145, and 165% of the baseline oral intake of each monkey were successively administered. During the initial overfeeding period (100% of the baseline oral intake), at least one week was required to reduce voluntary oral intake to less than 25% of the baseline levels and complete suppression of oral intake did not occur. This increased total caloric intake (IG infusion plus oral intake) resulted in a rapid rate of weight gain of at least 5 times the baseline rate. With successive increases in caloric infusion level, oral intake was eventually suppressed, and rapid weight gain was sustained. When the IG infusion was abruptly terminated after 50 to 130 days, 3 monkeys refused all food for 14 to 35 days. The monkeys' oral intakes stabilized three to ten weeks after the end of the overfeeding period. The length of this period prior to the resumption of normal oral intake was not related to length of overfeeding nor to the amount of weight gained. The monkeys' body weights dropped rapidly in the initial post-overfeeding period and then stabilized, sometimes at levels higher than their baseline body weights. In 2 monkeys, at the end of overfeeding the amounts infused were gradually reduced in order to determine the calories required to maintain their body weights at peak levels. Significantly fewer kcal/kg were required to maintain peak body weights than were ingested during the baseline periods.