AIMTo determining whether the level of serum leptin altered and whether the expression of leptin receptor immunoreactivity changed following taste stimuli.

METHODSAfter intraoral infusions of chemical solutions, which included 3 mol/L sucrose, 5 mmol/L sodium saccharin, 0.1 mol/L NaCl, 0.01 mol/L HCl, 1 mmol/L quinine H2SO4 and 0.1 mol/L monosodium glutamate, serum leptin concentration were measured by using rat leptin RIA kit. Immunohistochemistry ABC method was used for brain sections with high-specify-goat antiserum against leptin receptors.

RESULTSComparing with the control group (intraoral infusion of distilled water), the level of serum leptin only in sweet group (sucrose an d saccharin) raised (P < 0.05). Many neuronal cell bodies and dendritic processes showed leptin receptors immunoreactivity (LR-IR) in many brain regions, such as amygdala, hypothalamus, parabrachial nucleus and nucleus of the solitary tract, which had intense relationship with taste and feeding. But the number of positive-stained cells showed no difference in aforementioned brain regions between the taste stimuli group and the control group.

CONCLUSIONAfter intraoral stimuli of sweet substances, the serum leptin concentration increased. LR-IR cells exist in amygdala which plays a critical role in the initiation and guidance of feeding. This findings led us study possible effects of leptin on taste responses. Probably, leptin influences food intake through the sense of taste.

Animals ; Brain ; physiology ; Eating ; Female ; Leptin ; blood ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; blood ; Taste

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.
Amenorrhea/metabolism ; Animals ; Female ; Humans ; Leptin/blood/deficiency/genetics/*metabolism ; Male ; Neurosecretory Systems/*metabolism

Adolescent ; Adult ; Fatty Liver ; metabolism ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Leptin ; blood ; Male ; Middle Aged

OBJECTIVETo investigate the relationship between fasting serum levels of leptin, glucose, insulin resistance, lipids in simple obese children.

METHODSFasting serum levels of leptin and insulin (Fins) were measured by RIA in 42 obese and 42 normally-weighted children matched on age, sex and height, and their total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) were analyzed with enzymatic methods. HOMA-IR and LDL-C were calculated.

RESULTSSerum level of leptin was (2.74 - 45.12) micro g/L and (0.53 - 10.18) micro g/L in obese and normally-weighted children, respectively, with an average level of leptin (log) significantly higher in obese group than that in control group (P < 0.001). Serum level of leptin was positively correlated with BMI, WHR and percentage of body fat. Of obese children, 83% were leptin resistant. Serum levels of TC, TG, LDL-C and insulin were significantly higher in obese leptin-resistant group than those in normally-weighted control group, but no significant difference in them between obese leptin-sensitive group and its normally-weighted control group was observed. Significantly higher serum levels of TG and lower HDL-C were observed in obese leptin-resistant group, as compared with those in obese leptin-sensitive group.

CONCLUSIONSA big difference in serum level of leptin between obese and normally-weighted children was found, suggesting most obese children were resistant to endogenous leptin. Leptin resistance correlated significantly with the risk of metabolic syndrome and cardiovascular disease, indicating serum level of leptin could be used as an indicator in screening obese children at high risk.

Blood Glucose ; metabolism ; Body Mass Index ; Child ; Cholesterol ; blood ; Female ; Humans ; Insulin Resistance ; Leptin ; blood ; Male ; Obesity ; blood ; Triglycerides ; blood

In order to explore the effect and underlying mechanism of hypoxia on body weight, the effect of intermittent moderate hypoxia on high-fat diet-induced obesity was observed in mice, and the role of leptin in hypoxic effect was identified. Healthy Kunming mice were divided randomly into 4 groups (n=20 in each group). The control group: the mice were fed normally under the normal oxygen pressure. Hypoxia group: the mice were fed normally, and given intermittent moderate hypoxia training. Obesity group: the mice were fed diet rich in fat and sugar under the normal oxygen pressure. Hypoxia + obesity group: the mice were fed diet rich in fat and sugar, and given intermittent moderate hypoxia training. After 40 d of feeding and training, the body weight of mice was determined, and the average increasing rate of body weight in each group was calculated and normalized with food intake. Meanwhile, plasma leptin level was measured with ELISA method, and fatty degeneration and leptin receptor expression in liver were observed by Sudan III staining and immunohistochemistry, respectively. The obesity mouse model was successfully established with increases in body weight, plasma leptin level and distribution of adipocytes in the liver. The average body weight and density of adipocytes in the liver in hypoxia and hypoxia + obesity groups decreased obviously, while plasma leptin level and leptin receptor expression in the liver were increased. It is suggested that intermittent moderate hypoxia reduces body weight through elevating plasma leptin level and/or enhancing leptin receptor expression in the liver.
Adipocytes ; cytology ; Animals ; Body Weight ; Female ; Hypoxia ; metabolism ; pathology ; Immunohistochemistry ; Leptin ; blood ; Liver ; chemistry ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; Receptors, Leptin ; analysis

OBJECTIVETo evaluate the role of leptin in neointimal formation and related mechanisms.

METHODSFemoral arterial injury was induced in wild-type (Wt, n = 10), leptin-deficient (Lep(-)/-, n = 12), and leptin receptor-deficient (LepR(-)/-, n = 10) mice. Leptin treatment studies (tail vein injection of adenovirus expressing murine leptin on the RSV promoter, ad-leptin) were performed on Lep(-)/- (n = 5) and LepR(-)/- (n = 4) mice. Intimal (I) and medial (M) areas were measured and the ratio of I/M was calculated. Smooth muscle cells were detected by smooth muscle alpha-actin staining using an alpha-actin monoclonal antibody. Cellular proliferation was analyzed with BrdU Staining Kit and the number of BrdU-positive cells was counted manually. Plasma leptin level was measured by ELISA.

RESULTSThe I/M ratio of Lep(-)/- and LepR(-)/- mice was significantly lower than that in Wt separately (Lep(-)/- vs. Wt = 0.80 +/- 0.14 vs. 1.50 +/- 0.22, P < 0.01; LepR(-)/- vs. Wt = 0.55 +/- 0.20 vs. 1.50 +/- 0.22, P < 0.05). Plasma leptin level was significantly increased in Lep(-)/- and LepR(-)/- mice post leptin treatment. I/M was significantly increased in Lep(-)/- mice receiving ad-leptin compared with untreated Lep(-)/- mice (P < 0.05), while I/M was similar between LepR(-)/- mice with and without ad-leptin treatment (P > 0.05). The changes on number of positive alpha-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.

CONCLUSIONSMice lacking leptin or the leptin receptor were protected from neointimal formation following vascular injury. Leptin treatment increased neointimal formation in Lep(-)/- but not in LepR(-)/- mice, suggesting leptin receptor activation and vascular smooth muscle cell proliferation played a pivotal role on neointimal formation post-injury in this model, giving an evidence that high plasma leptin level is a risk factor for neointimal formation.

Actins ; analysis ; Animals ; Cell Proliferation ; Leptin ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular ; pathology ; Receptors, Leptin ; metabolism ; Tunica Intima ; pathology

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.
Adipose Tissue ; Blood-Brain Barrier ; Body Weight ; Brain ; Eating ; Endoplasmic Reticulum Stress ; Energy Metabolism ; Humans ; Hypothalamus ; Leptin ; Models, Animal ; Neurons ; Obesity ; Pro-Opiomelanocortin ; Receptors, Leptin ; Rodentia

OBJECTIVETo investigate the mechanism underlying the protective effects of a traditional Chinese medicinal formula, Baoganning, against liver fibrosis.

METHODSMale Wistar rats were subjected to injection of carbon tetrachloride- peanut oil mixture and given daily 5% alcoholic beverage, and 2 days after the injection, Baoganning was administered intragastrically at two different doses for 6 weeks. Radioimmunoassay was used to detect serum leptin level, and immunohistochemistry employed to examine the effect of Baoganning on expressions of leptin and its receptor in the liver tissue of the rats.

RESULTSCompared with the normal control group, the rats in the liver fibrosis model group and Baoganning-treated groups showed significantly increased serum leptin levels (P<0.01), and the serum leptin level was significantly lower in Baoganning group than in the liver fibrosis model group (P<0.01). Baoganning significantly reduced the hepatic expression of leptin and OB-Rb in rats with liver fibrosis in comparison with their expression in the model group (P<0.01).

CONCLUSIONBaoganning can effectively ameliorate liver fibrosis in rats possibly through reducing serum leptin level and inhibiting hepatic leptin and its receptor expressions.

Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Leptin ; blood ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; blood ; chemically induced ; prevention & control ; Male ; Phytotherapy ; Radioimmunoassay ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Leptin ; blood ; metabolism

OBJECTIVETo explore the factors influencing insulin resistance in children with different nutritional status during pubertal development.

METHODSThree hundred children with simple obese aged 7 to 17 years, and 300 normal healthy children and 300 children with malnutrition, matched for age (+/- 3 months) and height (+/- 2 cm), were selected. Fasting serum levels of leptin, insulin, glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured for them.

RESULTSLevels of fasting serum insulin in obese children, except for boys at Tanner stage I and girls at Tanner stage II, were higher than those in normal and malnutrition children (P < 0.01). Average serum level of leptin in obese boys and girls at varied Tanner stages was higher than that in normal children, and higher in normal children than that in children with malnutrition (P<0.01). Serum level of TG in obese children [(1.53 +/- 0.13) mmol/L] was higher than that in normal ones [(1.12 +/- 0.10) mmol/L] and in children with malnutrition [(1.03 +/- 0.09) mmol/L]. There was no significant difference in levels of fasting blood glucose and other blood lipids between the three groups of children. Insulin sensitivity decreased with pubertal development and its index reversely correlated with Tanner stage and serum level of leptin (r=-0.27 and -0.36, respectively, P<0.01).

CONCLUSIONObesity (BMI), serum level of leptin and pubertal development were independent risk factors for insulin resistance in children aged 7 to 17 years.

Adolescent ; Body Mass Index ; Child ; Estradiol ; blood ; Growth Hormone ; metabolism ; Humans ; Insulin ; blood ; Insulin Resistance ; Leptin ; blood ; physiology ; Male ; Malnutrition ; blood ; Obesity ; blood ; physiopathology ; Puberty ; physiology ; Testosterone ; blood

Animals ; Diet, High-Fat ; Glucagon ; blood ; Glucose ; metabolism ; Hormones ; blood ; Insulin ; blood ; Leptin ; blood ; Lipid Metabolism ; Male ; Rats ; Rats, Sprague-Dawley