Dieting is more effective in reducing weight but exercise is more effective in reducing fat during the early phase of a weight-reducing program in healthy humans

This study compared the relative effectiveness of two means of energy deficit, food restriction (FR) and increased physical activity (EX), on body weight, body composition and concentrations of serum leptin, insulin, glucose, and lipids in female subjects. Thirteen adult female volunteers participated in a two-phase crossover-treatment study. Each phase involved a 9-day energy deficit period and a 5-day follow up energy repletion period. A 25% energy deficit was achieved by either FR or EX. Baseline values were established prior to phase one. Results showed that FR had greater body weight loss, but less body fat loss compared to EX. FR and EX both reduced serum leptin, insulin, total triacylglycerol, LDL-C and VLDL-C concentrations. However, only EX elevated HDL-C. These effects were reversed during follow up energy repletion. Results suggest that under iso-caloric energy deficit conditions FR is more effective in reducing body weight but EX is more effective in reducing body fat and maintaining lean body mass. EX can lead to a more desirable blood lipid profile than can FR. Thus, it is desirable to include exercise in a weight reduction program.     

Effects of Exogenous Gonadal Steroids on Leptin Homeostasis in Rats

WU-PENG, SHARON, MICHAEL ROSENBAUM, MARGERY NICOLSON, STREAMSON C. CHUA, AND RUDOLPH L. LEIBEL. Effects of exogenous gonadal steroids on leptin homeostasis in rats. Obes Res. Background: In humans, circulating concentrations of the hormone leptin, normalized to body fat mass, are significantly higher in females compared to males. This experiment was designed to determine whether the administration of exogenous androgen or estrogen would significantly alter the relationship between plasma leptin and fat mass in rats. Methods: In the first experiment, plasma leptin and retro-peritoneal and parametrial (female)/epididymal (male) adipose tissue expression of leptin mRNA were measured in five male and five female 9. 5-week-old Sprague-Dawley rats. In a second experiment, gonadectomized 10. 5-week-old female Sprague-Dawley rats received 1 or 2 weeks of daily intraperitoneal injections (in oil) of 750 mg testosterone propionate, 2. 5 μg of estradiol benzoate or vehicle. At 0, 1, and 2 weeks, plasma concentrations of leptin, fat pad weight of parametrial and retroperitoneal fat pads, and leptin mRNA expression by Northern blot in retroperitoneal fat pads were determined. Daily weight and food intake of animals were monitored throughout the study. Results: Circulating leptin concentrations per unit of fat pad mass and leptin mRNA expression normalized to actin mRNA were higher in gonadally intact female compared to male rats. Compared to placebo, estrogen administration decreased food intake and body weight, but had no significant effect on leptin mRNA expression or on circulating leptin concentration. Testosterone administration increased body weight and decreased expression of leptin mRNA (only after 2 weeks), but did not change food intake or circulating leptin concentration. Conclusions: Administration of estrogen did not affect either leptin expression or the circulating concentration of leptin. Administration of androgen decreased expression of leptin mRNA. However, even after 2 weeks of testosterone administration to gonadectomized females, plasma leptin concentration, corrected for fat pad weight, was higher in gonadectomized females than in intact males, Thus, sex steroid-associated changes in plasma leptin concentration and leptin mRNA expression are not sufficient to explain the observed sexual dimorphism in plasma leptin concentrations in rats.     

Effects of perinatal maternal food restriction on pituitary-gonadal axis and plasma leptin level in rat pup at birth and weaning and on timing of puberty

The effects of maternal 50% food restriction (FR) during the last week of gestation and/or lactation on pituitary-gonadal axis (at birth and weaning), on circulating levels of leptin (at weaning), and on the onset of puberty have been determined in rats at birth and at weaning. Maternal FR during pregnancy has no effect at term on the litter size, on the basal level of testosterone in male pups, and on the drastic surge of circulating testosterone that occurs 2 h after birth. At weaning, similar retardation of body growth is observed in male and female pups from mothers exposed to FR. This undernutrition induces the most drastic effects when it is performed during both gestation and lactation or during lactation alone. Drastic retardation of testicle growth with reduction of cross-sectional area and intratubular lumen of the seminiferous tubules is observed in male pups from mothers exposed to undernutrition during both gestation and lactation or during lactation alone. Maternal FR during the perinatal period reduces circulating levels of FSH in male pups without affecting LH and testosterone concentrations. Maternal FR does not affect circulating levels of LH, estradiol, and progesterone in female pups. Female pups from mothers exposed to FR during both gestation and lactation show a significant increase of plasma FSH as well as a drastic retardation of ovarian growth. The follicular population was also altered. The number of antral follicles of small size (vesicular follicles) was increased, although the number of antral follicles of large size (graafian follicles) was reduced. Maternal FR occurring during both late gestation and lactation (male and female pups), during lactation alone (male and female pups), or during late gestation (female pups) induces a drastic reduction of plasma leptin and fat mass in pups at weaning. The onset of puberty is delayed in pups of both sexes from mothers exposed to FR during lactation and during both gestation and lactation. In conclusion, these data demonstrate that a perinatal growth retardation induced by maternal FR has long-term consequences on both size and histology of the genitals, on plasma gonadotropins and leptin levels, on fat stores at weaning, and on the onset of puberty.     

自愿转轮运动对雄性长爪沙鼠体重和能量代谢的影响

运动是影响动物能量平衡和体重变化的重要因素之一。为研究自愿转轮运动对体重和能量代谢的影响,我们监测了8 周自愿转轮运动过程中,雄性长爪沙鼠的体重、能量摄入、消化率、静止代谢率(RMR) 和非颤抖性产热(NST)的变化,以及8 周后的体脂含量、血清甲状腺激素(T3、T4 )和瘦素(leptin)水平的变化等。结果发现,8 周自愿转轮运动增加了长爪沙鼠的体重和能量摄入以及血清瘦素水平(血清瘦素浓度比对照组高27% ),但对消化率、RMR 和褐色脂肪组织的线粒体蛋白浓度等没有明显影响。尽管体脂含量和血清T₃ 和T₄ 没有显著差异,但运动组体脂含量比对照组高33%,血清T₃ 和T₄ 水平分别比对照组低10% 和38%。血清瘦素浓度与体脂重量呈正相关。因此,自动转轮运动并没有降低动物的体重和体脂含量,但瘦素和甲状腺素在雄性长爪沙鼠能量代谢和能量平衡中的作用尚需进一步确定。     

How cancellous and cortical bones adapt to loading and growth hormone

There is great interest in the relationships between growth hormone (GH), muscle loading and bone, in part, because GH increases muscle mass which provides the largest signals that control bone modeling and remodeling. This study was designed to examine the effects of GH and muscle loading by exercise (EX) independently and in combination on bone and skeletal muscle. Thirteen-month-old female F344 rats were divided into 6 groups: Group 1, baseline controls (B); Group 2, agematched controls (C); Group 3, GH treated (2.5 mg rhGH/kg b. wt/day, 5 days per week); Group 4, voluntary wheel running exercise (EX); Group 5, GH+EX, and rats in Group 6 were food restricted (FR) to lower their body weight and examine the effects of decreased muscle load on bone. All animals, except the baseline controls, were sacrificed after 4.5 months. Growth hormone increased the body weight and tibial muscle mass of the rats markedly, while EX caused a slight decrease in body weight and partially inhibited the increase caused by GH in the GH+EX group. Food restriction greatly decreased body weight below that of age-matched controls but neither FR nor EX had a significant effect on the mass of the muscles around the tibia. Growth hormone and EX independently increased tibial diaphyseal cortical bone area (p<0.0001), cortical thickness (p<0.0001), cortical bone mineral content (p<0.0001), periosteal perimeter (p<0.0001) and bone strength-strain index (SSI) (p<0.0001). The effects of GH were more marked, and the combination of GH and EX produced additive effects on many of the tibial diaphyseal parameters including bone SSI. GH+EX, but not GH or EX alone caused a significant increase in endocortical perimeter (p<0.0001). In the FR rats, cortical bone area and cortical mineral content increased above the baseline level (p<0.0001) but were below the levels for age-matched controls (p<0.0001). In addition, marrow area, endocortical perimeter and endocortical bone formation rate increased significantly in the FR rats (p<0.01, p<0.0001, p<0.0001). Three-point bending test of right tibial diaphysis resulted in maximum force (Fmax) values that reflected the group differences in indices of tibial diaphyseal bone mass except that GH+EX did not produce additive effect on Fmax. The latter showed good correlation with left tibial diaphyseal SSI (r=0.857, p<0.0001) and both indices of bone strength correlated well with tibial muscle mass (r=0.771, Fmax; r=0.700, SSI; p<0.0001). We conclude that the bone anabolic effects of GH with or without EX may relate, in part, to increased load on bone from tibial muscles and body weight, which were increased by the hormone. The osteogenic effects of EX with or without GH may relate, in part, to increased frequency of muscle load on bone as EX decreased body weight (p<0.05) but had no significant effect on tibial muscle mass. The enhanced loss of endocortical bone by FR may relate, in part, to decreased load on bone due to low body weight (p<0.0001) as FR did not cause a significant decrease in tibial muscle mass (p=0.357). The roles of humoral and local factors in the bone changes observed remain to be established.     

Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition

The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.     

Differential effect of long-term food restriction on fatty acid synthase and leptin gene expression in rat white adipose tissue.

Long-term food restriction (85%, 70% and 50% of ad libitum energy intake for one month) induced a substantial fall in serum leptin concentration and leptin mRNA levels in epididymal white adipose tissue in rats. Surprisingly, this suppression was not reversed by refeeding ad libitum for 48 h. The reduction in serum leptin concentration and leptin mRNA level did not strictly correlate with reduction in fat or body mass. Unlike serum leptin concentration and epididymal adipose tissue leptin mRNA levels, fatty acid synthase activity, fatty acid synthase protein abundance and fatty acid synthase mRNA levels increased significantly in white adipose tissue after refeeding rats subjected to food restriction. The increase in serum insulin concentration was observed in all groups on different degrees of food restriction and refed ad libitum for 48 h compared to controls. A decrease in serum insulin concentration was found in the rats not refed before sacrifice. Long-term food restriction did not significantly affect serum glucose concentrations in either refed or non-refed rats. The data reported in this paper indicate that there is no rapid rebound in serum leptin concentration or leptin gene expression in contrast to the increase in serum insulin concentration and fatty acid gene expression in white adipose tissue of rats refed ad libitum after one month's food restriction.     

Chronic exercise lowers the defended body weight gain and adiposity in diet-induced obese rats

The effects of running wheel exercise and caloric restriction on the regulation of body weight, adiposity, and hypothalamic neuropeptide expression were compared in diet-induced obese male rats over 6 wk. Compared with sedentary controls, exercising rats had reduced body weight gain (24%), visceral (4 fat pads; 36%) and carcass (leptin; 35%) adiposity but not insulin levels. Hypothalamic arcuate nucleus (ARC) proopiomelanocortin (POMC) mRNA expression was 25% lower, but ARC neuropeptide Y (NPY), agouti- related peptide, dorsomedial nucleus (DMN) NPY, and paraventricular nucleus (PVN) corticotropin- releasing hormone (CRH) expression was comparable to controls. Sedentary rats calorically restricted to 85% of control body weight reduced their visceral adiposity (24%), leptin (64%), and insulin (21%) levels. ARC NPY (23%) and DMN NPY (60%) were increased, while ARC POMC (40%) and PVN CRH (14%) were decreased. Calorically restricted exercising rats an half as much as ad libitum-fed exercising rats and had less visceral obesity than comparably restricted sedentary rats. When sedentary restricted rats were refed after 4 wk, they increased intake and regained the weight gain and adiposity of sedentary controls. While refed exercising rats and sedentary rats ate comparable amounts, refed exercising rats regained weight and adiposity only to the level of ad libitum-fed exercising rats. Thus exercise lowers the defended level of weight gain and adiposity without a compensatory increase in intake and with a very different profile of hypothalamic neuropeptide expression from calorically restricted rats. This may be due to exercise-related factors other than plasma insulin and leptin.     

Central application of IGF-1 postpones time of vaginal opening in normally fed, but not in food-restricted rats

BACKGROUND/AIMS: Central but also peripheral IGF-1 is suggested to play a role in the initiation of puberty as it directly affects GnRH synthesis and release. A possible intermediate in the effects of IGF-1 on puberty might be the adiposity-signaling hormone leptin, whose plasma levels are decreased in food-restricted (FR) rats. METHODS: IGF-1 was chronically centrally infused in 23-day-old prepubertal female rats which were either normally fed or 30% FR, and the effects on time of vaginal opening (VO) and plasma leptin levels were monitored. RESULTS: FR treatment postponed time of VO and decreased plasma leptin levels. In normally fed rats centrally infused with IGF-1, time of VO was found to be postponed to the same extent as FR treatment did. The IGF-1 infusion did not affect plasma leptin levels in normally fed animals but increased leptin levels in the FR group compared to controls. Daily food intake was equal between all groups but body weight course was lower in FR rats. IGF-1 treatment did not significantly affect food intake or body weight course. CONCLUSION: FR treatment delays the moment of vaginal opening to the same extent as observed in normally fed rats that were centrally infused with IGF-1.     

High-fat diet offsets the long-lasting effects of running-wheel access on food intake and body weight in OLETF rats

We have previously demonstrated that running-wheel access normalizes the food intake and body weight of Otsuka Long-Evens Tokushima Fatty (OLETF) rats. Following 6 wk of running-wheel access beginning at 8 wk of age, the body weight of OLETF rats remains reduced, demonstrating a lasting effect on their phenotype. In contrast, access to a high-fat diet exacerbates the hyperphagia and obesity of OLETF rats. To determine whether diet modulates the long-term effects of exercise, we examined the effects of high-fat diet on food intake and body weight in OLETF rats that had prior access to running wheels for 4 wk. We found that 4 wk of running exercise significantly decreased food intake and body weight of OLETF rats. Consistent with prior results, 4 wk of exercise also produced long-lasting effects on food intake and body weight in OLETF rats fed a regular chow. When running wheels were relocked, OLETF rats stabilized at lower levels of body weight than sedentary OLETF rats. However, access to a high-fat diet offset these effects. When OLETF rats were switched to a high-fat diet following wheel relocking, they significantly increased food intake and body weight, so that they reached levels similar to those of sedentary OLETF rats fed a high-fat diet. Gene expression determination of hypothalamic neuropeptides revealed changes that appeared to be appropriate responses to the effects of diet and running exercise. Together, these results demonstrate that high-fat diet modulates the long-lasting effects of exercise on food intake and body weight in OLETF rats.     

Increased weight gain after ovariectomy is not a consequence of leptin resistance

The positive correlation between leptin and body fat mass has caused some investigators to speculate that leptin resistance contributes to obesity. Loss of ovarian function in human and rat is associated with increased fat mass gain and increased circulating leptin levels. To study whether ovariectomy produces leptin resistance, Sprague-Dawley female rats were ovariectomized or sham operated and injected with leptin for 35 days. Ovariectomy (OVX) produced hyperphagia and increased gain in both lean and fat mass. Daily leptin injections initially decreased food intake significantly, but feeding gradually increased to a stable level by day 16 and remained at that level for the duration of study. Body composition analysis indicated that chronic injection of leptin to OVX rats dramatically decreased (P < 0.05) fat mass [30 +/- 2 (SE) g, vehicle, to 3 +/- 1 g, leptin]. Using indirect calorimetry, we observed that OVX did not change energy expenditure or total level of fuel utilization. Leptin administration increased fat utilization and prevented reduction in calorie expenditure that is typically associated with food restriction. Leptin treatment to OVX rats decreased plasma triglyceride, free fatty acid, and insulin concentrations, whereas glucose concentration was normal. Withdrawal of leptin triggered hyperphagia, indicating that leptin biology remained throughout the duration of the chronic treatment. The same dose of leptin produced qualitatively similar data in sham-operated rats. Thus we concluded that the loss of ovarian function in rats is not associated with a change in leptin sensitivity.     

The effects of prior weight reduction on the running wheel-induced feeding suppression in rats

Adult male rats given ad lib access to food and a running wheel show an initial feeding and weight suppression. Over 6-10 days feeding recovers, but body weight remains low. It is not clear which effect is primary, the wheel-induced feeding or weight change. To test this, rats were first restricted to 15 g of food a day for 8 or 16 days to reduce their weight relative to control non-restricted rats. They were then returned to ad lib feeding and half the restricted and non-restricted control rats were introduced to the wheel either immediately (Experiment 1) or 4 days later (Experiment 2). Food intake, body weight, and wheel running were monitored throughout the experiments. At the return to ad lib feeding, prior food restriction elevated feeding. Both immediate and delayed wheel access suppressed feeding in both groups of wheel access rats compared to the appropriate control rats. Feeding history did not have a significant effect on wheel running. The wheel-induced reductions in feeding from baseline were similar in the weight reduced and normal weight animals suggesting that prior weight restriction did not prevent the onset of the wheel-induced feeding suppression. It is therefore suggested that the feeding suppression is not driven by a reduced weight set point.     

The role of leptin in striped hamsters subjected to food restriction and refeeding

Food restriction(FR) and refeeding(Re) have been suggested to impair body mass regulation and thereby making it easier to regain the lost weight and develop over-weight when FR ends. However, it is unclear if this is the case in small mammals showing seasonal forging behaviors. In the present study, energy budget, body fat and serum leptin level were measured in striped hamsters that were exposed to FR-Re. The effects of leptin on food intake, body fat and genes expressions of several hypothalamus neuropeptides were determined. Body mass, fat content and serum leptin level decreased during FR and then increased during Re. Leptin supplement significantly attenuated the increase in food intake during Re, decreased genes expressions of neuropepetide Y(NPY) and agouti-related protein(AgRP) of hypothalamus and leptin of white adipose tissue(WAT). Hormone-sensitive lipase(HSL) gene expression of WAT increased in leptin-treated hamsters that were fed ad libitum, but decreased in FR-Re hamsters. This indicates that the adaptive regulation of WAT HSL gene expression may be involved in the mobilization of fat storage during Re, which partly contributes to the resistance to FR-Re-induced overweight. Leptin may be involved in the down regulations of hypothalamus orexigenic peptides gene expression and consequently plays a crucial role in controlling food intake when FR ends.     

Sex differences in voluntary locomotor activity of food-restricted and ad libitum-fed rats. Implications for the maintenance of a body weight set-point

1. Male and female Wistar-strain rats were studied under either ad libitum or 23-hour food restriction conditions both with and without access to a running wheel. 2. Daily measures were taken of body weight, food consumption and wheel revolutions. 3. It was observed that food restriction was associated with decreased food consumption and body weight but increased wheel revolutions. 4. Irrespective of feeding regime, females exhibited higher running rates than males.     

Plasma adiponectin is increased in mice selectively bred for high wheel-running activity, but not by wheel running per sé.

Mice selectively bred for high wheel-running activity (S) have decreased fat content compared to mice from randomly bred control (C) lines. We explored whether this difference was associated with alterations in levels of circulating hormones involved in regulation of food intake and energy balance, and whether alterations were caused by the presence of a running wheel. Plasma levels of leptin, adiponectin, and corticosterone as well as body composition were analyzed in male S mice housed with (+) and without (-) access to running wheels at ages of 10 and 18 months. These levels were compared to those found in C+ mice. Plasma corticosterone did not differ among groups. While plasma leptin levels tended to be lower in S+ mice as compared to S- or C+ mice, these differences were largely attributable to differences in fat content. Adiponectin levels were increased in S mice (+60%) compared to C mice, irrespective of wheel access. High levels of this hormone may be a trait co-segregated in mice bred for high wheel-running activity.     

Three weeks of early-onset exercise prolongs obesity resistance in DIO rats after exercise cessation

We assessed the effect of early-onset exercise as a means of preventing childhood obesity using juvenile male rats selectively bred to develop diet-induced obesity (DIO) or to be diet resistant (DR) when fed a 31% fat high-energy diet. Voluntary wheel running begun at 36 days of age selectively reduced adiposity in DIO vs. DR rats. Other 4-wk-old DIO rats fed a high-energy diet and exercised (Ex) for 13 wk increased their core temperature, gained 22% less body weight, and had 39% lighter fat pads compared with sedentary (Sed) rats. When wheels were removed after 6 wk (6 wk Ex/7 wk Sed), rats gained less body weight over the next 7 wk than Sed rats and still had comparable adipose pad weights to 13-wk-exercised rats. In fact, only 3 wk of exercise sufficed to prevent obesity for 10 wk after wheel removal. Terminally, the 6-wk-Ex/7-wk-Sed rats had a 55% increase in arcuate nucleus proopiomelanocortin mRNA expression vs. Sed rats, suggesting that this contributed to their sustained obesity resistance. Finally, when Sed rats were calorically restricted for 6 wk to weight match them to Ex rats (6 wk Rstr/7 wk Al), they increased their intake and body weight when fed ad libitum and, after 7 wk more, had higher leptin levels and adiposity than Sed rats. Thus, early-onset exercise may favorably alter, while early caloric restriction may unfavorably influence, the development of the hypothalamic pathways controlling energy homeostasis during brain development.     

Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction

Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. These studies examine the relationship between insulin responsiveness and visceral fat in MR and test whether, despite lower food intake observed in MR animals, decreased visceral fat accretion and preservation of insulin sensitivity is not secondary to CR. Accordingly, rats pair fed (pf) control diet (0.86% methinone, CF) to match the food intake of MR for 80 weeks exhibit insulin, glucose, and leptin levels similar to control-fed animals and comparable amounts of visceral fat. Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF. In a separate cohort, insulin responses of older MR animals as measured by oral glucose challenge are similar to young animals. Longitudinal assessments of MR and CF through 112 weeks of age reveal that MR prevents age-associated increases in serum lipids. By 16 weeks, MR animals show a 40% reduction in insulin-like growth factor-1 (IGF-1) that is sustained throughout life; CF IGF-1 levels decline much later, beginning at 112 weeks. Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.     

Reduced central leptin sensitivity in rats with diet-induced obesity

On low-fat chow diet, rats prone to diet-induced obesity (DIO) have increased arcuate nucleus neuropeptide Y (NPY) expression but similar leptin levels compared with diet-resistant (DR) rats (19). Here, body weight and leptin levels rose in DIO rats, and they defended their higher body weight after only 1 wk on a 31% fat high-energy (HE) diet. However, DIO NPY expression did not fall to DR levels until 4 wk when plasma leptin was 168% of DR levels. When switched to chow, DIO rats lost carcass fat (18). By 10 wk, leptin levels fell to 148% and NPY expression again rose to 150% of DR levels. During 4 wk of food restriction, DIO leptin fell by approximately 50% while NPY increased by 30%. While both returned to control levels by 8 wk, DIO rats still regained all lost weight when fed ad libitum. Finally, the anorexic effect of intracerebroventricular leptin (10 microg) was inversely correlated with subsequent 3-wk weight gain on HE diet. Thus NPY expression and food intake are less sensitive to the leptin's suppressive effects in DIO rats. While this may predispose them to develop DIO, it does not fully explain their defense of a higher body weight on HE diet.     

Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition

Maternal nutrient restriction results in intrauterine growth restriction (IUGR) newborns that develop obesity despite normal postweaning diet. The epidemic of metabolic syndrome is attributed to programmed "thrifty phenotype" and exposure to Western diets. We hypothesized that programmed IUGR newborns would demonstrate greater susceptibility to obesity and metabolic abnormalities in response to high-fat diet. From day 10 to term gestation and lactation, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques resulted in three offspring groups: control (AdLib/AdLib), FR during pregnancy (FR/AdLib), and FR during lactation (AdLib/FR). At 3 weeks, offspring were weaned to laboratory chow or high-fat calorie diet (9% vs. 17% calorie as fat). Body composition, appetite hormones, and glucose and lipid profiles were determined in 9-mo-old male and female offspring. High-fat diet had no effect on body weight of AdLib/AdLib, but significantly increased weights of FR/AdLib and AdLib/FR offspring. High-fat diet significantly increased body fat, reduced lean body mass, and accentuated plasma leptin but not ghrelin levels in both sexes in all groups. In males, high-fat diet caused a significant increase in glucose levels in all three groups with increased insulin levels in AdLib/AdLib and AdLib/FR, but not in FR/AdLib. In females, high-fat diet had no effect on glucose but significantly increased basal insulin among all three groups. High-fat diet caused hypertriglyceridemia in all three groups although only food-restricted females exhibited hypercholesterolemia. Sex and offspring phenotype-associated effects of high-fat diet indicate differing pathophysiologic mechanisms that require specific therapeutic approaches.     

Voluntary exercise contributed to an amelioration of abnormal feeding behavior,locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague–Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.