Acute physical exercise increases leptin-induced hypothalamic extracellular signal-regulated kinase1/2 phosphorylation and thermogenesis of obese mice

The obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal-regulated kinase-1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin-induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin-induced hypothalamic p-ERK1/2 and uncoupling protein 1 (UCP1) content in BAT ( P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO ₂) and heat production in obese exercised mice ( P < 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin-induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice.     

Comparison of plasma leptin and zinc levels in elite athletes and sedentary people

In consideration of leptin effects such as reducing food intake and increasing energy consumption, many researchers have sought to examine the relation between leptin and exercise. The presence of reports arguing that zinc, can be a mediator in leptin production indicates a possible relation between zinc and leptin. The present study aims to determine plasma leptin levels in elite weightlifters and examine their relation with zinc. The study enrolled 30 healthy volunteers in the 18-27 age range. The subjects were allocated to groups in equal numbers: Group 1, Control Group: the group included subjects who did not exercise regularly. Group 2, Elite Weightlifter Group: the group included elite weight lifters who were selected to the national team in their weight classes, who exercised regularly and whose values were measured during rest in the training period. Levels of plasma leptin and zinc were determined in the blood samples collected from the subjects included in the study. Comparison of serum leptin and zinc values between groups showed that leptin and zinc levels in the control group were significantly higher than those in the weightlifters and that leptin levels decreased significantly in parallel with the low zinc levels. It can be concluded that physical activity brings about changes in leptin secretion, which in turn, can be significantly related with zinc (p < 0.01).     

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

To assess the importance of the sympathetic nervous system in regulating body weight during prolonged leptin infusion, we evaluated food intake, body weight, and physical activity in conscious, unrestrained rats. Initial studies illustrated that prolonged intracerebroventricular (ICV) infusion of leptin enhanced substrate oxidation so that adipose tissue lipid stores were completely ablated, and muscle triglyceride and liver glycogen stores were depleted. After neonatal chemical sympathectomy, changes in weight and food intake were compared in groups of sympathectomized (SYM) and control (CON) adult animals during ICV infusion of leptin. CON animals lost 60 +/- 9 g over 10 days vs. 25 +/- 3 g in the SYM animals when food intake was matched between the two groups. Greater weight loss despite similar energy intake points to an important role of the sympathetic nervous system in stimulating energy expenditure during ICV leptin infusion by increasing the resting metabolic rate, since no differences in physical activity were observed between CON and SYM groups. In conclusion, activation of the SNS by leptin increases energy expenditure by augmenting the resting metabolic rate.     

Leptin, gastrointestinal and stress hormones in response to exercise in fasted or fed subjects and before or after blood donation.

Leptin, an ob gene product of adipocytes, plays a key role in the control of food intake and energy expenditure but little is known about leptin response to strenuous exercise in fasted and fed subjects or before and after blood donation. This study was designed to determine the immediate effects of strenuous exercise in healthy volunteers under fasting or fed conditions and before and one day after blood donation (450 ml) on plasma levels of leptin and gut hormones [gastrin, cholecystokinin (CCK), pancreatic polypeptide (PP) and insulin], as well as on "stress" hormones (cortisol, catecholamines and growth hormone. Two groups (A and B) of healthy non-smoking male volunteers were studied. All subjects performed incremental exercise tests until exhaustion (up to maximal oxygen uptake--VO2max), followed by 2 h of rest session. Group A perfomed the tests on a treadmill, while group B on a cycloergometer. In group A, one exercise was performed under fasting conditions and the second following ingestion of a standard liquid meal. In group B, one exercise test was performed as a control test and the second 24 h after blood donation (450 ml). Blood samples were withdrawn 5 min before the start of the test, at the VO2max, and 2 h after finishing the exercise. No significant change in plasma teptin were observed both immediately and 2 h after the exercise in fasted subjects, but after the meal the plasma leptin at VO2max and 2 h after the test was significantly higher, while after blood donation was significantly reduced. The postprandial rise in plasma leptin was accompanied by a marked increment in gut hormones; gastrin, CCK and PP and stress hormones such as norepinephrine, cortisol and GH. These hormonal changes could contribute to the postprandial rise in plasma leptin concentrations, while the fall of leptin after blood donation could be attributed to the inadequate response of stress hormones and autonomic nervous system to exhausting exercise. We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation and 3) following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, cortisol and GH concentrations, possibly due to the impairment in the autonomic nervous control of these hormones.     

Leptin effect in ob/ob mice under thermoneutral conditions depends not necessarily on central satiation

Energy expenditure in ob/ob mice kept at thermoneutrality was quantified from food intake and body composition of mice treated with leptin over 15 and 75 days, respectively. Energy expenditure in response to 15 days of treatment with leptin was twice as high as under pair-feeding conditions, indicating extensive breakdown of adipose tissue independent of a centrally mediated satiation. Leptin-induced reduction of food intake ceased during treatment with leptin over 75 days, when the lipid reserves of the mice were depleted and energy expenditure became similar to that in lean mice. Energy mobilized in leptin-treated ob/ob mice from endogenous lipid resources and similar to the food energy consumed in hyperphagic ob/ob controls may cause satiation. Maximal energy expenditure in both groups may correspond to their energy supply: energy expenditure in ob/ob mice was shown to be correlated to the food intake in the absence of leptin. Leptin effects observed in ob/ob mice under thermoneutral conditions may modify the traditional view of the functionality of the hormone.     

Effect of physical training on the responses of serum adrenocorticotropic hormone during prolonged exhausting exercise

The purpose of this study was to investigate the effects of physical training on the responses of serum adrenocorticotropic hormone (ACTH) and cortisol concentration during low-intensity prolonged exercise. Five subjects who had fasted for 12 h cycled at the same absolute intensity that elicited 50% of pre-training maximal oxygen uptake (VO2max), either until exhaustion or for up to 3 h, before and after 7 weeks of vigorous physical training [mean daily energy consumption during training exercise, 531 kcal (2230 kJ)]. In the pretraining test, serum ACTH and cortisol concentrations did not increase during the early part of the exercise. Increases in concentrations of both hormones occurred in all subjects when blood glucose concentration decreased during the later phase of the exercise. The mean values and SEM of serum ACTH and cortisol concentrations at the end of the exercise were 356 ng.l-1, SEM 79 and 438 micrograms.l-1, SEM 36, respectively. After the physical training, VO2max of the subjects improved significantly from the mean value of 50.2 ml.kg-1.min-1, SEM 2.5 to 57.3 ml.kg-1.min-1, SEM 2.0 (P less than 0.05). In the post-training test, exercise time to exhaustion was prolonged in three subjects. Comparing the pre- and post training values observed after the same length of time that the subjects had exercised in the pre-training test, the post-training values of serum ACTH (44 ng.l-1, SEM 3) and cortisol (167 micrograms.l-1, SEM 30) concentration were less than the pre-training value (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma leptin concentration during different types of exercises performed by horses

Leptin is a tissue-derivative adipokine that regulates appetite, food intake and energy expenditure. It is still not clear how exercise affects plasma leptin concentration in horses. The aim of this study was to evaluate the influence of exercise intensity and duration on plasma leptin levels in working horses. A total of 38 horses were prospectively included in the study and grouped according to the type of exercise they performed: dressage (six stallions, group D), jumping (12 stallions, group J), race (12 Thoroughbred horses, six stallions and six mares, group R) and harness (10 light draft stallions, group H). Blood samples were taken both before and after routine exercise (immediately after the exercise, 30 min and 24 h after). Blood lactic acid (LA) and plasma concentration of leptin, cortisol, uric acid, triacylglycerols, glycerol and free fatty acids were determined. Immediately after exercise, group R had the highest level of LA, whereas groups D and J had the lowest levels. A significant increase in plasma leptin concentration was stated only in group H in samples taken immediately after the end of the exercise period and 30 min after the exercise period, as compared with the values obtained at rest. A significant increase in plasma cortisol concentration was found immediately after the end of the exercise period in groups R and H. Leptin exercise-to-rest ratio was significantly correlated with cortisol exercise-to-rest ratio (r=0.64; P<0.001). The increase in plasma leptin concentration in exercised horses was related to the increased plasma cortisol concentration and took place only during long-lasting exercise, which was not intensive.     

The Response to Exercise with Constant Energy Intake in Identical Twins

Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 ± 9.8 MJ (Mean ± SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p <0.001) and it was entirely accounted for by the loss of fat mass (p <0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p <0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomography (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm² (SEM = 5) to 52 cm² (SEM = 6) (p <0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p <0.05). Intrapair resemblance was observed for the changes in body weight (p <0.05), fat mass (P <0.01), percent fat (p <0.01), body energy content (p <0.01), sum of 10 skinfolds (p <0.01), abdominal visceral fat (p <0.01), fasting plasma triglycerides (p <0.05) and cholesterol (p <0.05), maximal oxygen uptake (p <0.05), and respiratory exchange ratio during submaximal work (p <0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during sub-maximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months.     

Cellular adaptations in fat tissue of exercise-trained miniature swine: role of excess energy intake.

This study examined the influence of energy expenditure and energy intake on cellular mechanisms regulating adipose tissue metabolism. Twenty-four swine were assigned to restricted-fed sedentary, restricted-fed exercise-trained, full-fed sedentary, or full-fed exercise-trained groups. After 3 mo of treatment, adipocytes were isolated and adipocyte size, adenosine A(1) receptor characteristics, and lipolytic sensitivity were measured. Swine were infused with epinephrine during which adipose tissue extracellular adenosine, plasma fatty acids, and plasma glycerol were measured. Results revealed that adipocytes isolated from restricted-fed exercised swine had a smaller diameter, a lower number of A(1) receptors, and a greater sensitivity to lipolytic stimulation, compared with adipocytes from full-fed exercised swine. Extracellular adenosine levels were transiently increased on infusion of epinephrine in adipose tissue of restricted-fed exercised but not full-fed exercised swine. These results suggest a role for adenosine in explaining the discrepancy between in vitro and in vivo lipolysis findings and underscore the notion that excess energy intake dampens the lipolytic sensitivity of adipocytes to beta-agonists and adenosine, even if accompanied by exercise training.     

The effect of fasting and physical exercise on plasma leptin concentrations in high-fat fed rats.

The aim of our study was to estimate the effect of fasting and physical exercise on a treadmill on plasma leptin concentrations in high-fat fed rats. Male Wistar rats were injected a low dose of streptozotocin (STZ) or buffer at 2 days of age and later fed a standard or high-fat diet (HFD). Plasma leptin was measured by RIA method in all the groups studied in basal conditions, after 48h fasting, a single bout of exhaustive exercise, and 4 weeks of exercise training. Plasma leptin concentrations were markedly elevated in the HFD and STZ/HFD groups compared to the control group. The significant correlation between plasma leptin and body weight was noted. Fasting and exercise training decreased plasma leptin in similar percentage in all the groups studied. The observed decrease was greater than expected from changes in body weight. We conclude that high-fat feeding results in an increase in plasma leptin levels in rats independently of plasma insulin or daily calorie intake. High-fat fed rats have maintained leptin response to fasting and exercise training. The reduction in plasma leptin after exercise training is partly independent on changes in body weight or plasma insulin.     

The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load

Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity.     

Plasma levels of interleukin-6 and interleukin-18 after an acute physical exercise: relation with post-exercise energy intake in twins

Increased interleukin-6 (IL-6) plasma levels have been described to occur during physical exercise. A relative reduction in energy intake after physical activity has also been reported after exercise, indicating a possible involvement of IL-6 as an anorexigenic factor. Given the possible effect of interleukins on appetite, we assessed whether a controlled physical activity bout is related with changes in IL-6, IL-6 soluble receptor (IL-6sR), gp130 and interleukin-18 (IL-18) plasma levels, as well as their relation with post-exercise energy intake. A co-twin intervention study was carried out with five young male monozygotic twin pairs. One co-twin performed 45 min of submaximal exercise on a treadmill near the anaerobic threshold ending with 7 min at 90 % VO₂ max, while his co-twin remained non-active. Ad libitum energy intake was tested through a carbohydrate-rich meal test. Venous blood samples were drawn at baseline, immediately after exercise and after the meal ingestion. Plasma concentrations of IL-6, IL-6sR, gp130 and IL-18 were measured via ELISA. IL-6 plasma levels increased after physical activity bout (2.6-fold change; p?=?0.04). A less marked trend, although still significant, was observed for plasma levels of IL-6sR and gp130. Plasma levels of IL-18 did not significantly change during exercise. The twins who exercised exhibited significantly lower energy intake (181 versus 1,195 kcal; p?=?0.04), compared to the co-twins who remained resting. The present study in monozygotic twins shows increased IL-6 plasma levels after acute physical exercise with a significant reduction in energy intake, supporting a linkage between IL-6 and acute post-exercise eating behaviour.     

Changes in blood cell response following strenuous physical exercise.

The generation of tumour necrosis factor (TNF) and tissue factor activity in lipopolysaccharide (LPS) stimulated blood were studied in 25 healthy subjects before and after physical exercise of different intensities. Of the subjects a group of 9 were athletes who trained once to twice every day of the week, a second group of 8 exercised 3-7 times a week, and a third group of 8 exercised 4-5 times a month. The production of TNF in freshly drawn LPS stimulated blood in heparin, drawn from top athletes at rest was significantly lower than in the other subjects. The LPS induced concentrations of TNF-alpha of 2.73 (SEM 1.05) ng.ml-1 in the blood of the top athletes compared to 5.08 (SEM 0.7) ng.ml-1 and 7.6 (SEM 1.6) ng.ml-1, respectively, in the other two groups. The group that trained the least had the highest values. Immediately after exercise, the monocytes appeared to be less responsive to LPS stimulation, as a reduction of 47%-48% was observed in the top athletes and in the other group of well-trained individuals. The group that trained the least, which was also subjected to the least stressful exercise, had a 33% reduction in TNF production. Within 6 h the TNF concentration was back to pre-exercise values. Within 6 h the TNF concentration was back to pre-exercise values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

长期强迫运动对大绒鼠体重、能量代谢和血清瘦素的影响

动物稳定体重的维持需要能量摄入和消耗之间的平衡。运动是影响动物能量平衡的重要因素之一。为了解运动对大绒鼠(Eothenomys miletus)的生理学效应,在室内条件下,测定了强迫运动训练(运用小鼠封闭跑台)8周后大绒鼠的体重、代谢率、摄入能、血清瘦素和身体组成的变化。结果显示,强迫运动训练8周对大绒鼠的体重无显著影响;大绒鼠的代谢率和摄入能均显著增加,训练8周后静止代谢率较对照组增加了29.9%,运动最大代谢率较对照组增加了10.7%;强迫运动训练8周组的身体脂肪重量比对照组降低了28.9%,血清瘦素水平比对照组下降了27.4%,对照组的瘦素与体脂含量具有明显的相关性,但运动组则不具有相关性;运动组的肝重量和消化道重量较对照组均显著增加;而体水重量则显著降低。这些结果表明,在强迫运动训练期间大绒鼠主要通过动员储存的脂肪、增加代谢率和食物摄入的方式来维持自身的体重及能量平衡。瘦素在长期强迫运动过程中对身体脂肪含量的变化具有调节作用。     

Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women

Because the effect of exercise on leptin was not established, we controlled energy intake (I) and exercise energy expenditure (E) to distinguish the independent effects of energy availability (A = I - E) and exercise stress (everything associated with exercise except its energy cost) on the diurnal leptin rhythm in healthy young women. In random order, we set A = 45 and 10 kcal. kg lean body mass(-1) (LBM) x day(-1) for 4 days during the early follicular phase of separate menstrual cycles in sedentary (S, n = 7) and exercising (X, n = 9: E = 30 kcal x kg LBM(-1) x day(-1)) women. Low energy availability suppressed the 24-h mean (P < 10(-6)) and amplitude (P < 10(-5)), whereas exercise stress did not (both P > 0.2). Suppressions of the 24-h mean (-72 +/- 3 vs. -53 +/- 3%, P < 0.001) and amplitude (-85 +/- 3 vs. -58 +/- 6%, P < 0.001) were more extreme in S vs. X than previously reported effects on luteinizing hormone pulsatility and carbohydrate availability. Thus the diurnal rhythm of leptin depends on energy, or carbohydrate, availability, not intake, and exercise has no suppressive effect on the diurnal rhythm of leptin beyond the impact of its energy cost on energy availability.     

Energy balance in exercise-trained rats acclimated at two environmental temperatures

The present study was carried out to investigate the effects of exercise training on energy balance in male rats acclimated at two different environmental temperatures. Sedimentary and exercised rats were housed and trained at either 24 or 4 degrees C, with the training program consisting of running on a motor-driven treadmill within their respective environments. After 45 days, energy, protein, and fat contents of rats were determined together with the energy content of food and feces. The results show that metabolizable energy intake was reduced by 10% in exercise-trained groups. Substantial differences in energy gains were observed between sedentary and trained rats; sedentary rats showed almost three times more energy gain than trained rats. Carcass analysis revealed the energy gain differences to be mainly due to varied amounts of fat deposition. Energy expenditure (kJ) excluding the cost of exercise training was corrected for metabolic body size (BW 0.75), which in turn showed no significant differences between trained rats and their respective sedentary controls. The present results suggested that exercise training in rats leads to neither increase nor decrease in energy expenditure through components additional to physical activity. The present results also indicated that brown adipose tissue thermogenesis, as assessed through mitochondrial guanosine 5'-diphosphate binding, was not significantly modified by exercise training, regardless of the temperature at which the rats were housed and trained.     

Leptin and exercise

Short-term exercise (<60 min) studies suggest that leptin concentrations are not acutely affected in healthy males and females. Most reports of reductions in serum leptin may be attributed to circadian rhythms or hemoconcentration. For long-term (> or =60 min) exercise, a reduction in leptin concentrations reported from 1 to 3 hr of running or cycling has been attributed to diurnal reduction in circulating leptin, independent of exercise. Exercise that produces a sufficient energy imbalance (kilocalorie intake versus kilocalorie expenditure) suppresses 24-hr mean and amplitude of the diurnal rhythm of leptin in women. Suppression of leptin concentrations may be counterbalanced by feeding and may explain consistent reports of reductions in leptin concentrations following extreme bouts of exercise such as marathons or ultramarathons. In addition, leptin concentrations are reduced 48 hr after long-term aerobic exercise and long-term resistance exercise is associated with delayed leptin reduction 9 hr postexercise. Training studies have documented that short-term exercise training (< or =12 weeks) does not affect leptin levels, with the exception of patients with type 2 diabetes. Exercise training protocols that result in reduced fat mass will lower leptin concentrations, thus, most investigators have reported leptin concentrations after accounting for fat loss. There are disparate findings concerning long-term (>12 weeks) training studies, with a number of studies finding no effect of training on leptin concentrations other than effects induced by fat loss, and other studies finding reductions in leptin concentrations after accounting for fat loss. Exercise training-induced reductions in leptin levels have been attributed to alterations in energy balance, improvements in insulin sensitivity, alterations in lipid metabolism, and unknown factors. Hormone replacement does not seem to affect leptin adaptations to training. Patients with type 2 diabetes show delayed effects of short-term resistance exercise on leptin concentrations, reduced leptin levels with long-term training, and appear to be more sensitive to training-induced leptin adaptations than other populations.     

Central Exercise Action Increases the AMPK and mTOR Response to Leptin

AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus.     

Localization and role of leptin in the thyroid gland of the lizard Podarcis sicula (Reptilia, Lacertidae)

Leptin, the product of the ob gene, is a hormone secreted by adipocytes that regulates food intake and energy expenditure. The hypothalamus-pituitary-thyroid axis is markedly influenced by the metabolism status, being suppressed during food deprivation. The present study was designed to ascertain whether (1) lizard thyroid gland expresses the long form of leptin receptor (Ob-Rb) and (2) the leptin administration affects the thyroid gland activity in this species (and to verify whether leptin plays a similar role in reptiles as observed in the other vertebrates). The presence of leptin receptor in the thyroid gland of Podarcis sicula was demonstrated by immunohistochemical technique (avidin-biotin-peroxidase complex--ABC method). The role of leptin in the control of thyroid gland activity was studied in vivo using light microscopy (LM) technique coupled to a specific radioimmunoassay for thyroid-stimulating hormone (TSH) and thyroid hormones (T4 and T3). Leptin (0.1 mg/100 g body wt)/day increased T4 and T3 release for 3 days but decreased the plasma concentration of TSH; using LM clear signs of stimulation in the thyroid gland were observed. These findings suggest that systemic administration of leptin stimulates the morphophysiology of the thyroid gland in the lizard through a direct mechanism involving Ob-Rb.