Seasonal changes in plasma leptin concentration related to antler cycle in Iberian red deer stags

The aim of this study is to describe the leptin cycle in male Iberian red deer (Cervus elaphus hispanicus) and relate it to antler and testosterone cycles. An additional aim is to assess the relationship between the plasma leptin concentration during antlers’ growth and their final size. Therefore, blood from 21 Iberian red deer males was sampled monthly to analyse leptin and testosterone. At the same time the deer were weighed and their body condition was assessed. The length of antlers was measured every 2 weeks and, after casting, their final length and perimeters were taken. Leptin showed a seasonal cycle, with a peak in June that decreased as testosterone increased. Low values were observed in autumn, winter and early spring. The relationship observed between leptin and body mass or body condition score was different in spring, when plasma testosterone concentration is low, than in autumn, when testosterone increases. Leptin peak amplitude was positively related to final antler size. In conclusion, the relationship between leptin and body mass and body condition score changes through the year, possibly due to the influence of androgens and photoperiod. There was a positive relationship between plasma concentration of leptin during antler growth and final antler length.     

Plasma leptin decreases during lactation in insectivorous bats

We previously demonstrated high leptin levels during late pregnancy in little brown bats (Myotis lucifugus). We now extend these observations to a second species, the big brown bat (Eptesicus fuscus), and also report that leptin increases after the first trimester of pregnancy. Leptin decreased to baseline 1 week following parturition, with a half-time decay of 2 days. During lactation, leptin was significantly correlated with body mass in E. fuscus, but not in M. lucifugus. No circadian pattern of leptin was observed in M. lucifugus. The decrease in post-partum leptin in bats may be partly explained by loss of putative placental leptin. The continued decrease may reflect depletion of body fat during this energy demanding period, at least in Eptesicus. Changes in leptin during lactation appeared to be independent of circadian effects and time of sampling. Our study provides additional evidence that leptin increases during pregnancy and declines during lactation in a free-ranging mammal, supporting the hypothesis that leptin plays important but yet undetermined roles in reproduction. Accepted: 4 October 1998     

Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women

To evaluate the effect of menopausal status and body mass index (BMI) on circulating leptin and adiponectin concentrations and investigate whether there is an influence of menopausal transition on the relationships of these adipokines and leptin to adiponectin (L/A) ratio with lipid profile and insulin resistance in a sample of Tunisian women. One hundred ninety-six premenopausal (mean age 35.3 ± 7.6 years) and 180 postmenopausal women (mean age 53.4 ± 6.2 years) were included in the study. Participants were stratified into obese and normal weight groups based upon their baseline BMI. Fasting glucose, HDL-cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), insulin, leptin, and adiponectin concentrations were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Premenopausal women had significantly higher leptin and L/A ratio and lower adiponectin levels than postmenopausal women. Menopause had no effect on the mean values of BMI, insulin or HOMA-IR, HDL-C, and TG. Using a multiple linear regression model, menopausal status was identified, as significant independent predictor for leptin and adiponectin levels. Irrespective of the menopausal status, obese women exhibited higher leptin and L/A ratio and lower adiponectin levels compared to those with normal weight. Comparison between the two menopausal stages in obese and normal weight groups showed that leptin and L/A ratio decreased, while adiponectin increased from pre- to postmenopausal stage only in obese group. The L/A ratio correlated better with lipid profile and HOMA-IR in postmenopausal stage. The present study showed a significant interaction between menopause and BMI on leptin and adiponectin secretion. Menopausal transition affects the relationships of these adipokines with lipids and insulin resistance.     

Effect of exercise training on total daily physical activity in elderly humans

This study examined the effect of 12 weeks of exercise training on daily physical activity in elderly humans. Training consisted of a weekly group session and an individual session with cardio- and weight-stack machines. A group of 15 subjects served as the exercise group [EXER mean age 59 (SD 4) years], and 7 subjects as the controls [CONT mean age 57 (SD 3) years]. Physical activity and physical fitness were measured before the start of training (T), at week 6 and week 12 (T0, T6, T12 respectively) in EXER, and at T0 and T12 in CONT. Physical activity over 14 days was measured using a tri-axial accelerometer and physical fitness was measured during an incremental exercise test. At T12, mean maximal power output had significantly increased in EXER compared to CONT 8 (SD 12) vs -5 (SD 9) W; P < 0.02] and mean submaximal heart rate (at 100 W) had reduced [-10 (SD 7) vs -2 (SD 6) beats x min(-1); P < 0.05]. No differences or changes in physical activity were observed between EXER and CONT. At T6, physical activity on training days was significantly higher than on non-training days (P < 0.001). When the accelerometer output of the training session was subtracted from the accelerometer output on training days, at T12 non-training physical activity was significantly lower than on non-training days (P < 0.004). Accelerometer output of the individual training session at T12 had significantly increased compared to T6 (P < 0.05), whereas, accelerometer output of the group training session had remained unchanged. In conclusion, in elderly subjects an exercise training programme of moderate intensity resulted in an improved physical fitness but had no effect on total daily physical activity. Training activity was compensated for by a decrease in non-training physical activity.     

Effects of aerobic exercise on serum leptin levels in obese women

It has been demonstrated that leptin concentrations in obese patients may be altered by weight loss. We examined the effects of a 9-week aerobic exercise program on serum leptin concentrations in overweight women (20-50% above ideal body mass) under conditions of weight stability. Sixteen overweight women, mean (SE) age 42.75 (1.64) years, comprised the exercise group which adhered to a supervised aerobic exercise program. A graded exercise treadmill test was conducted before and after the exercise program to determine maximal oxygen uptake (VO2max) using open-circuit spirometry. The women demonstrated improved aerobic fitness (VO2max increased 12.29%), however, body fat and the body mass index did not change significantly [42.27 (1.35)-41.87 (1.33)%]. Fourteen women, age 40.57 (2.80) years, did not exercise over the same time period and served as a control group. Serum leptin levels were not significantly altered for either the exercise [28.00 (2.13)-31.04 (2.71) ng x ml(-1)] or the control group [33.24 (3.78)-34.69 (3.14) ng x mg(-1)]. The data indicate that 9 weeks of aerobic exercise improves aerobic fitness, but does not affect leptin concentrations in overweight women.     

Effects of elevated plasma noradrenaline concentration on the immune system in humans

This study was designed to test the hypothesis that elevated plasma noradrenaline concentrations contribute to the exercise-induced modulation of the activity and percentage of the natural killer (NK) cells, and the leucocyte concentration. In a single blind, controlled, cross-over study, eight healthy men had noradrenaline infused for 1 h and achieved plasma noradrenaline concentrations comparable (20-fold increment) to those previously observed in cycle ergometer exercise (75% of maximal oxygen uptake for 1 h). The noradrenaline infusion increased the unstimulated, the interleukin-2 and interferon-alpha stimulated NK cell activity, and the percentage of CD16+ cells. The natural lytic activity per CD16+ cell however, did not change. The concentration of neutrophils, lymphocytes and CD16+ cells increased during the infusion. The neutrophil concentration remained elevated 2 h after infusion, at which time the lymphocyte count was back to normal. These results are comparable with the effects in the exercise model, and it is suggested that the augmented plasma noradrenaline concentrations, seen during extreme exercise, may participate in the exercise-induced immune changes.     

Short photoperiod influences energy intake and serum leptin level in Brandt's voles (Microtus brandtii)

Photoperiod cues play important roles in the regulation of seasonal variations in body mass (BM) and energy balance for many small mammals. The present study was designed to examine the effects of photoperiod acclimation on BM, energy intake, and serum leptin levels in Brandt's voles (Microtus (Lasiopodomys) brandtii). After 4 weeks of acclimation to either long (LD; light:dark, 16:8) or short (SD; 8:16) photoperiod, SD voles had lower BM, body fat mass, and dry mass of liver and kidneys, but higher digestible energy intake in comparison to LD voles. SD voles also showed a lower level of serum leptin than did LD voles. Furthermore, the level of serum leptin was correlated positively with body fat mass and negatively with gross energy intake. Together, these data suggest that Brandt's voles employ a strategy of minimizing body growth, increasing energy intake, and mobilizing fat deposition in response to cues associated with short photoperiod. Furthermore, leptin seems to be involved in the regulation of BM and energy balance mediated by photoperiod.     

The effects of age on uptake, serum half-life and bioavailability of mouse [D-Leu-4]OB3, a synthetic peptide amide with leptin-like activity, in male C57BL/6J mice

We have previously shown that the activity of a synthetic peptide amide corresponding to amino acid residues 116–130 of mouse leptin is contained in a restricted sequence at the amino terminus of the peptide, between residues 116 and 122 (Ser-Cys-Ser-Leu-Pro-Glu-Thr). This peptide was named mouse OB3. The potency of OB3 was improved by replacing the l-leucine residue at position four with its d-isomer. Intraperitoneal administration (ip) of mouse OB3 or [D-Leu-4]OB3 to ob/ob and db/db mice reduces food intake, body weight gain and serum glucose levels, and enhances insulin sensitivity. These effects of OB3 and [D-Leu-4]OB3 are very pronounced in young mice and diminish with age. In the present study, we measured uptake, serum half-life, and bioavailability of mouse [D-Leu-4]OB3 in mice of different ages. Groups of male C57BL/6J mice, six and 25 weeks of age, were given a single ip injection of 1 mg mouse [D-Leu-4]OB3 in PBS. Five, 10, 20, 40, 60, 120, or 180 min after injection, the mice were anesthetized and exsanguinated. Serum samples were prepared and assayed for mouse [D-Leu-4]OB3 content by competitive ELISA. In six week-old mice, the maximum concentration of mouse [D-Leu-4]OB3 was reached in 10 min, and the serum half-life was approximately 52.5 min. In 25 week-old mice, however, mouse [D-Leu-4]OB3 peaked in 5 min, and the serum half-life was approximately 30.6 min. The relative bioavailability of mouse [D-Leu-4]OB3 in six and 25 week-old mice was determined by measuring the area under the uptake curves. Bioavailability of mouse [D-Leu-4]OB3 was approximately 20% greater in six week-old mice than in 25 week-old mice. The results of this study indicate that at least some pharmacokinetic parameters of peptide uptake change as mice age. They also suggest that differences in uptake, serum half-life, and relative bioavailability of mouse [D-Leu-4]OB3 may contribute, at least in part, to the reduced efficacy of bioactive leptin-related peptides we have consistently observed in ob/ob and db/db mice as they age.     

PARADOXICAL POST-EXERCISE RESPONSES OF ACYLATED GHRELIN AND LEPTIN DURING A SIMULATED NIGHT SHIFT

Approximately 10% of employees undertake night work, which is a significant predictor of weight gain, possibly because responses to activity and eating are altered at night. It is known that the appetite-related hormone, acylated ghrelin, is suppressed after an acute bout of exercise during the day, but no researcher has explored whether evening exercise alters acylated ghrelin and other appetite-related outcomes during a subsequent night shift. Six healthy men (mean?±?SD: age 30?±?8 yrs, body mass index 23.1?±?1.1?kg/m²) completed two crossover trials (control and exercise) in random order. Participants fasted from 10:00?h, consumed a test meal at 18:00?h, and then cycled at 50% peak oxygen uptake or rested between 19:00–20:00?h. Participants then completed light activities during a simulated night shift which ended at 05:00?h. Two small isocaloric meals were consumed at 22:00 and 02:00?h. Venous blood samples were drawn via cannulation at 1?h intervals between 19:00–05:00?h for the determination of acylated ghrelin, leptin, insulin, glucose, triglyceride, and non-esterified fatty acids concentrations. Perceived hunger and wrist actimetry were also recorded. During the simulated night shift, mean?±?SD acylated ghrelin concentration was 86.5?±?40.8 pg/ml following exercise compared with 71.7?±?37.7 pg/ml without prior exercise (p?=?0.015). Throughout the night shift, leptin concentration was 263?±?242 pg/ml following exercise compared with 187?±?221 pg/ml without prior exercise (p?=?0.017). Mean levels of insulin, triglyceride, non-esterified fatty acids, and wrist actimetry level were also higher during the night shift that followed exercise (p?<?0.05). These data indicate that prior exercise increases acylated ghrelin and leptin concentrations during a subsequent simulated night shift. These findings differ from the known effects of exercise on acylated ghrelin and leptin during the day, and therefore have implications for energy balance during night work. (Author correspondence: c.j.morris@2006.ljmu.ac.uk).     

The effects of wintertime undernutrition on plasma leptin and insulin levels in an arctic ruminant, the reindeer

We examined the effects of prolonged undernutrition on plasma leptin and insulin levels and some serum protein metabolites in reindeer (Rangifer tarandus tarandus L.) during winter and spring. The reindeer (male < 1 year) were fed their preferred winter feed, low-protein lichen ad libitum for 5 weeks, followed by 40% restriction of energy for 8 weeks and refeeding with high-protein pellets for 6 weeks. The control group received high-protein reindeer pellets ad libitum throughout the experiment. Plasma leptin decreased by 46% and insulin by 54% in the lichen group already during the ad libitum period between January and February, with parallel decreases in body weight, serum total proteins, albumin and urea. Leptin remained low during most of the energy restriction period in March and April, but increased at the end of April while body weight decreased. During the refeeding period in May and June, the body weight and insulin of the lichen group increased in parallel with total proteins and urea, but leptin remained unchanged. Similar significant reductions in plasma leptin (40%) as in the lichen group also took place in the control group fed high-protein pellets ad libitum in January and February, although their feed intake, serum total proteins and body weight remained unchanged. The results show that leptin decreases in reindeer during mid-winter, independent of food or protein intake, and suggest that the decrease may be cued by seasonal factors such as the short photoperiod.     

Physiological predictors of leptin vary during menses and ovulation in healthy women

Although research has shown interactions between the reproductive system and energy homeostasis, it is not clear how environmental or behavioral factors may factor into these associations. Here we aimed to determine how changes in reproductive state (i.e., phase of the menstrual cycle) and other behavioral and physiological factors may influence leptin levels in healthy women, as well as how sexual activity may play a role in leptin modulation. We collected serum and saliva from 32 healthy women and measured leptin, estradiol, and progesterone. Participants also completed surveys of demographics, health and sexual behaviors, and physical activity. Leptin was predicted by meals per day and missed meals at both menses and ovulation. However, estradiol and physical activity were stronger predictors of leptin at menses, while sexual activity was a stronger predictor of leptin at ovulation. These findings suggest that predictors of serum leptin, and possibly energy storage and expenditure, vary across the menstrual cycle.     

Central leptin differentially modulates ultradian secretory patterns of insulin, leptin and ghrelin independent of effects on food intake and body weight

We tested the hypothesis that leptin acts centrally to differentially modulate the ultradian communication of leptin, insulin and ghrelin with the hypothalamus. The ultradian fluctuation of these hormones in plasma after central leptin gene therapy was analyzed. Increased leptin transgene expression in the hypothalamus significantly decreased energy intake and body weight concomitant with severe hypoleptinemia and hypoinsulinemia resulting from drastically suppressed peak heights with unchanged frequency discharge of these hormones. Ghrelin secretion was, however, increased solely due to increased pulse amplitude. In pair-fed control rats leptin and ghrelin secretion was unchanged. In conclusion, independent of restraint on caloric intake and weight, leptin acting centrally modulates only the pulse amplitude of ultradian rhythmicity of the three afferent signals involved in the hypothalamic integration of energy balance. Since rhythmic discharge patterns dictate target response of hormones, these findings reveal a novel hypothalamic action of leptin in the pathophysiology of the obesity-dependent metabolic syndrome.     

Effect of repeated bouts of short-term exercise on plasma free and sulphoconjugated catecholamines in humans

We tested the hypothesis that measurement of plasma catecholamine sulphate concentration after exercise reflects the overall activation of the sympathoadrenergic system during the whole period of repeated bouts of short-term exercise. A group of 11 male athletes performed two exercise tests at similar average power outputs consisting of three sets each. The tests either started with one set of three very intense sprints (95% of maximal running speed) followed by two sets of three less intense sprints (85% of maximal running speed; HLX) or vice versa (LHX). Similar mean areas under the curve of free noradrenaline (NA) during HLX and LHX [622 (SEM 13) v.s. 611 (SEM 14) nmol x l(-1) min) as well as similar mean heart rates [143 (SEM 9) v.s. 143 (SEM 8) beats x min(-1)] indicated comparable sympathetic activation during both exercise tests. Even so, plasma concentration of free NA was still significantly higher at the end of LHX than of HLX [35.7 (SEM 3.5) v.s. 22.5 (SEM 2.1) nmol x l(-1), respectively], i.e. when exercise ended with the more intense set of sprints. Plasma noradrenaline sulphate (NA-S) increased with exercise intensity showing higher mean increments after the first set of HLX compared to LHX [1.83 (SEM 0.42) v.s. 1.18 (SEM 0.29) nmol x l(-1); P<0.05]. However, after the end of HLX and LHX, increments in plasma NA-S were similar [4.52 (SEM 0.76) v.s. 4.06 (SEM 0.79) nmol x l(-1)], suggesting that NA-S response changed in parallel with the overall activation of the sympathetic nervous system during repeated bouts of short-term exercise. The results supported the hypothesis that measurement of plasma NA-S immediately after repeated bouts of short-term exercise reflects overall activation of the sympathetic nervous system during prolonged periods of this type of exercise.     

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population

Background

This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.

Methods

Convenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

The LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.

Conclusions

The LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.     

Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc plays an important role in appetite regulation also. Our aim is to evaluate the relationship between leptin and zinc in obese and nonobese type 2 diabetic patients and its relationship with oxidative stress and insulin. We studied 25 nonobese nondiabetic women (controls); 35 nonobese diabetic women; and 45 obese diabetic women. Plasma leptin concentration was determined by immunoradiometric assay. Thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, were assayed by the spectrofotometric method. Plasma levels of zinc and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence methods, respectively. We found that nonobese diabetic patients had significantly lower zinc and higher TBARS levels than control subjects (P<0.01). There was no difference in plasma leptin levels between nonobese diabetic subjects and controls. Obese diabetic subjects had significantly higher plasma leptin, TBARS, and insulin levels and significantly lower plasma zinc levels than nonobese diabetic subjects (for each comparison; P<0.01). The univariate and multivariate analyses demonstrated a significant positive correlation between leptin and body mass index (P<0.01) and insulin (P<0.01), and a significant negative correlation between leptin and zinc in obese subjects. Additionally, TBARS levels was positive correlated with insulin and negative correlated with zinc in obese diabetic subjects. We conclude that zinc may be a mediator of the effects of leptin, although the detailed mechanism is still unknown and requires further investigation. Free radical induced mechanism(s) may be involved in this process.     

Metabolic control of puberty: Roles of leptin and kisspeptins

This article is part of a Special Issue “Puberty and Adolescence”.     

Effect of intracerebroventricular infusion of leptin on the secretory activity of the GnRH/LH axis in fasted prepubertal lambs

Leptin is believed to link metabolic status to reproductive processes. The aim of the present study was to investigate the effect of exogenous leptin on the secretory activity of GnRH/LH system in acutely undernourished prepubertal, female lambs. Merino lambs were randomly divided into four groups, two standard-fed and two fasted for 72 h. One standard and one fasted groups were infused intracerebroventricularly (i.c.v.) with the vehicle; the remaining standard and fasted groups were infused with leptin (25 μg/120 μl/h). Leptin was administered in series of four 1-h infusions at 30-min intervals for 3 consecutive days from 08:30 to 14:00 h. Blood samples were collected on day 0 (before infusions) and on day 3 every 10 min over a 6-h period. Immediately after the experiment, the sheep were slaughtered and brains fixed in situ. Hypothalamic and pituitary tissues were prepared for further immunohistochemical and hybridization in situ analysis. In fasted sheep, increased GnRH levels in the median eminence (P < 0.001) and LHβ levels in the pituitary cells (P < 0.001) plus decreased LHβ mRNA and LH pulsatility in blood plasma were observed (P < 0.05). In leptin-infused fasted sheep, GnRH levels in the median eminence decreased (P < 0.001), LHβ mRNA hybridization signal increased, LHβ levels decreased in the pituitary cells (P < 0.001) and LH pulsatility increased (P < 0.05) in the blood plasma. These results indicate that, in prepubertal sheep, the GnRH/LH axis is sensitive to the fasting signal, that influence of which can be reversed by leptin. Leptin cancels out the suppressing effect of fasting on LH secretion by augmentation of GnRH.