Leptin levels and body composition of mice selectively bred for high voluntary locomotor activity

Selective breeding produced four replicate lines of high-runner (HR) mice that run on wheels for approximately 2.7 times more revolutions per day than four unselected control lines. Previous studies found that HR mice of both sexes have lower body fat (isotope dilution at 15 wk of age) and that males (females not studied) have smaller retroperitoneal fat pads (17 wk). HR mice also exhibit elevated plasma corticosterone and insulin-stimulated glucose uptake by some hindlimb muscles but apparently do not differ in circulating insulin or glucose levels (males at 18 wk). Given their lower body fat and higher activity levels, we hypothesized that HR mice would have lower circulating leptin levels than controls. Female mice were given wheel access for 6 d at 7 wk of age, as part of the routine wheel testing for the selective breeding protocol, and then were killed after one additional week without wheels to reduce possible acute effects of activity on leptin. As hypothesized, serum leptin levels were significantly lower in HR mice. ANCOVA indicated that leptin was strongly positively correlated with both total body fat (measured by ether extraction) and body mass change from weaning, but HR mice still had significantly lower adjusted leptin levels (ANCOVA). Within HR lines but not within control lines, individual variation in leptin levels was negatively correlated with amount or speed of wheel running measured a week before being killed. Growth from weaning to euthanasia and body dry mass were lower in HR mice than in controls, but absolute dry masses of the ventricles, liver, gut, and uterus plus ovaries did not significantly differ, nor did percentage of the total dry mass as fat. HR mice offer a novel model for studying the causes and consequences of physiologically relevant variations in serum leptin.     

Energy expenditure and locomotor activity in mice selected for food intake adjusted for body weight

Summary The aim of this study was to examine the differences in physical activity and their contribution to differences in energy utilization in mice, selected either high or low for food intake, adjusted for body weight, which show correlated responses in lean content and metabolic rate. Simultaneous measurements of fasting metabolic rate and activity were made in lines of mice selected at either: a young age, 4-to 6-week food intake corrected for 4-week body weight; or an older age, 8- to 10-week food intake corrected for mean weight at 8 and 10 weeks of age. Correlated response in metabolic rate was found to have been accompanied by changes in locomotor activity near the ages at selection in both sets of lines. Activity, however, accounted for only a small proportion of variation in fasting heat production, generally less than 5%, although a highly positive correlation (r=0.63) between the two traits was found. It was concluded that selection for food intake adjusted for body weight has led to correlated response in physical activity. In consequence, mice selected in the upward direction expend some of the excess energy intake rather than assimilating it as body mass and are, therefore, slightly leaner than their counterparts selected in the downward direction.     

The effect of insulin on circadian rhythm of voluntary locomotor activity in rats

Effects of single intranasal administration of 0.2 ng insulin at different moments of the projected daily cycle (ZT = 1, ZT = 7, ZT = 13 and ZT = 19) on the circadian rhythms of voluntary locomotor activity (wheel-running) were studied in Wistar male rats. Insulin administered at ZT-7 or ZT-13 induced a statistically significant phase advance by 4.4 and 5.5 hours, respectively. The administration of insulin at ZT-13 additionally induced a reduction of the period of the circadian rhythm of voluntary locomotor activity. Intranasal administration of insulin at other moments of the projected daily cycle (ZT = 1 or ZT = 19) did not induce any statistically significant change in phase or period duration of the circadian rhythms. Insulin did not cause changes in total daily activity irrespective of administration time. The results of the study suggest the role of endogenous insulin as entrainment factor for circadian oscillator in absence of the main physiological zeitgeber--cyclic afferent input from retina photoreceptors.     

Sex differences in the lipolytic activity of Galleria mellonella fat body

The sexual differences in the intensity of production and release of free fatty acids (FFA) as well as the differences in the absolute amount of FFA produced and released from the fat body are most conspicuous at the sixth day after the larval-pupal ecdysis. Furthermore, it is demonstrated that a significant difference exists in the lipolytic activity of the fat body between the two sexes.     

Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats

Acute administration of peptide YY(3-36) [PYY(3-36)] results in a reduction in food intake in several different vertebrates. However, long-term continuous administration of PYY(3-36) causes only a transient reduction in food intake, thus potentially limiting its therapeutic efficacy. We hypothesized that a fall in leptin levels associated with reduced food intake could contribute to the transient anorectic effects of continuous PYY(3-36) infusion and thus that leptin replacement might prolong the anorectic effects of PYY(3-36). Seven-day administration of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) using osmotic minipumps caused a significant reduction in food intake of ad libitum-fed rats, but only for the first 2 days postimplantation. Circulating levels of leptin were reduced 1 day following continuous infusion of PYY(3-36), and combined leptin infusion at a dose of leptin that had no anorectic effects on its own (100 microg x kg body wt(-1) x day(-1)) prolonged the anorectic actions of PYY(3-36) in ad libitum-fed rats for up to 6 days postimplantation and yielded reduced weight gain compared with either peptide alone. The inhibitory effects of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) on food intake were absent in rats refed after a 24-h fast and substantially reduced at a dose of 1,000 microg x kg body wt(-1) x day(-1) PYY(3-36). Leptin replacement was unable to recover the anorectic effects of PYY(3-36) in fasted rats. Our results suggest that an acute fall in leptin levels is not solely responsible for limiting duration of action of chronic PYY(3-36) infusion, yet chronic coadministration of a subanorectic dose of leptin can extend the anorectic effects of PYY(3-36).     

Sex differences in weight in infancy and the British 1990 national growth standards.

OBJECTIVES: To determine if there is a sex difference in infancy in the new British national standards for weight (based on data from 1990). DESIGN: Weight data in a birth cohort were compared with the 1990 standards and Tanner and Whitehouse (1966) standards up to age 12 months. SETTING: Newcastle upon Tyne. SUBJECTS: 3418 term infants. RESULTS: Our cohort showed a mean difference in standard deviation scores of 0.42 between boys and girls (P < 0.0001) when compared with the 1990 standards. Two and a half times as many girls as boys had weights below the 3rd centile during the first year, with an equivalent excess of boys above the 97th centile (P < 0.0001). Similar results were found with Tanner and Whitehouse standards. CONCLUSIONS: These differences could result in substantial sex bias in the identification of poor growth in early childhood. The standards need modification.     

Sex differences in the pharmacokinetics of pioglitazone in rats

Clinical studies have suggested that pioglitazone, an insulin sensitizer, has a stronger effect in women than in men. To determine the sex difference in the pharmacokinetics of pioglitazone, we examined the plasma and white adipose tissue levels of pioglitazone and its active metabolites (M-II, M-III and M-IV) in male and female rats treated with a single or repeated oral administration of pioglitazone (10 mg/kg). The AUCs of pioglitazone (149.6+/-22.6 vs. 103.3+/-14.0 microg.h/ml; P<0.01), M-III (31.4+/-8.1 vs. 20.2+/-4.7 microg.h/ml; P<0.05) and M-IV (41.9+/-15.5 vs. 14.1+/-1.6 microg.h/ml; P<0.01) were larger in female rats than in male rats, but the levels of M-II were similar. Any of the compounds did not accumulate in plasma after repeated administration. According to kinetic model analysis, the apparent elimination rate of pioglitazone and the formation rate of M-II were faster in male rats than in female rats. No significant sex difference was found in the tissue-to-plasma concentration ratios of pioglitazone or its active metabolites in white adipose tissue. These results suggest that there are sex differences in the plasma levels of pioglitazone and some of its active metabolites and that those differences are reflected in differences in white adipose tissue levels.     

Central complex substructures are required for the maintenance of locomotor activity in Drosophila melanogaster

In Drosophila melanogaster, former studies based on structural brain mutants have suggested that the central complex is a higher control center of locomotor behavior. Continuing this investigation we studied the effect of the central complex on the temporal structure of spontaneous locomotor activity in the time domain of a few hours. In an attempt to dissect the internal circuitry of the central complex we perturbed a putative local neuronal network connecting the four neuropil regions of the central complex, the protocerebral bridge, the fan-shape body, the noduli and the ellipsoid body. Two independent and non-invasive methods were applied: mutations affecting the neuroarchitecture of the protocerebral bridge, and the targeted expression of tetanus toxin in small subsets of central complex neurons using the binary enhancer trap P[GAL4] system. All groups of flies with a disturbed component of this network exhibited a common phenotype: a drastic decrease in locomotor activity. While locomotor activity was still clustered in bouts and these were initiated at the normal rate, their duration was reduced. This finding suggests that the bridge and some of its neural connections to the other neuropil regions of the central complex are required for the maintenance but not the initiation of walking. Accepted: 21 June 1999     

Sex differences in the cholinergic status of white rats]

Female rats injected with organophosphate inhibitor of acetylcholinesterase chlorophose at doses of 10 mg/kg and 360 mg/kg showed less considerable decrease in blood acetylcholinesterase activity than did male animals. Females compared with males also demonstrated less expressed clinical symptoms of poisoning (salivation, convulsion) after injection of chlorophose at dose of 360 mg/kg. The value of LD50 in female rats was 860 mg/kg, whereas the comparable value in male animals was 700 mg/kg. Following the injection of atropine at doses of 0.1, 0.3, 0.6 mg/100 g female rats showed 2-3 fold increases in basal adrenal and plasma corticosterone levels, but significant decreases in stress-induced corticosterone levels. As for males, the basal and stress-induced values of corticosterone were not significantly affected by atropine administration. These results suggest that functional reserves of cholinergic system and responsiveness of the hypothalamic-pituitary-adrenal axis to cholinergic influence are greater in females than in males. It is concluded that cholinergic status is significantly higher in female rats than in male ones.     

Effect of gender differences and voluntary exercise on antioxidant capacity in rats

The effects of gender difference and voluntary exercise on antioxidant capacity in rats were evaluated. The subjects were divided into two groups, physically active and sedentary. In the sedentary group, the level of hydroxyl radical in the liver was higher (P<0.001) in male rats than in female rats, however, in the physically active group, the level in male rats was lower (P<0.05) than in female rats. The levels of reduced glutathione (GSH) in physically active males and females were higher compared to those in the sedentary group. The physically active group also showed an increase in antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase activities. The level of liver GSH was higher in physically active females than in physically active males. For both groups, GPx and GR activities in females were significantly higher than in males. These results indicate that female rats have an intrinsically higher antioxidant capacity, which resulted in increased levels of GSH via the glutathione redox cycle and gamma-glutamyl cycle enzymes. The adaptation to altered antioxidant capacity, induced by physical activity, appeared to be affected by gender differences.     

Sex differences in reserve capacity of the pituitary-adrenal system in rats

Female rats exposed to complex emotional stress for 1 hour (restriction in the penal, vibration, loud dissonance music, interrupt light) simultaneously showed more considerable increases in plasma and adrenal corticosterone values than did male animals. Female rat corticosterone levels returned to basal values within 20-120 minutes of stressor-off. As for males the processes of restoration were delayed and accompanied by a 6-fold decrease in the plasma corticosterone levels compared with basal values. The response to additional acute stress (immobilization for 10 minutes) in various times after termination of complex emotional stress (0, 40, 120, 180, 240 minutes) was facilitated in females and remained unchanged in males. Plasma corticosterone levels under stressful conditions were 2-4-fold higher in females than in males. It is concluded that reserve capacity of adaptation system is significantly higher in female rats than in male ones.