The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete gamma-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate gamma-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases.
Bone Remodeling/physiology ; Bone and Bones/*metabolism ; *Energy Metabolism ; Humans ; Leptin/metabolism ; Osteocalcin/genetics/*metabolism

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

Despite a higher incidence and less favorable outcome of malignant tumors in obese patients, much less recognized is the link between obesity and cancer. The mechanism of the association of obesity with carcinogenesis remains incompletely understood. Postulated mechanisms include insulin resistance, insulin-like growth factor signaling, chronic inflammation, immunomodulation, hyperglycemia-induced oxidative stress, and changes of intestinal microbiome. Insulin resistance leads to direct mitogenic and antiapoptotic signaling by insulin and the insulin-like growth factor axis. Obesity can be considered to be a state of chronic low-grade inflammation. In obesity, numerous proinflammatory cytokines are released from adipose tissue which may involve in carcinogenesis. Hyperglycemia in susceptible cells results in the overproduction of superoxide and this process is the key to initiating all damaging pathways related to diabetes. This hyperglycemia-induced oxidative stress could be one possible link among obesity, diabetes, and cancer development. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention.
Adipokines/metabolism/physiology ; Gastrointestinal Neoplasms/*etiology/microbiology ; Humans ; Inflammation/etiology ; Insulin/metabolism/physiology ; Leptin/metabolism/physiology ; Obesity/*complications/immunology/metabolism ; Oxidative Stress ; Somatomedins/metabolism/physiology

For the regulation of energy balance in various internal organs including gut, pancreas and liver, visceral adipose tissue and brain perform important sensing and signaling roles via neural and endocrine pathway. Among these, adipose tissue has been known as a simple energy-storing organ, which stores excess energy in triglyceride. However, it became apparent that adipocytes have various receptors related to energy homeostasis, and secrete adipocytokines by endocrine, paracrine and autocrine mechanisms. In this review, basic roles of adipocytes in energy homeostasis and the correlation between adipocyte signals and digestive diseases are discussed.
Adipocytes/*metabolism ; Adipokines/*physiology ; Adiponectin/physiology ; Digestive System Diseases/*metabolism ; *Energy Metabolism ; Homeostasis ; Humans ; Leptin/physiology ; Peroxisome Proliferator-Activated Receptors/physiology ; Resistin/physiology ; Signal Transduction

OBJECTIVESTo study the role of leptin in the development boys during their puberty and its relationship with insulin (INS), growth hormone (GH), estradiol (E2) and testosterone (T).

METHODSOne hundred and fifty boys with simple obese aged 7 to 17 years, 150 normal healthy boys and 150 boys with malnutrition matched for age (+/- 3 months) and height (+/- 2 cm) were selected. Serum levels of leptin, INS, GH, E2 and T were measured for them.

RESULTSSerum level of leptin in obese group was significantly higher than that in normal group, and that in normal group was significantly higher than that in malnourished group. In the all three groups, serum level of leptin increased with age first until peak value, then began to decrease, with peak value of 6.96 microg/L at ages of 10-11 y in obese group, 10.25 microg/L at ages of 11-12 y in normal group and 5.08 microg/L at ages of 11-12 y in malnourished group. Serum level of leptin increased steadily from Tanner stages G1 to G2, then began to decrease steadily in G2 to G4. Serum level of leptin increased again in stage G5. Serum level of INS in boys increased steadily with age from 7 to 17 years old. Serum levels of GH, T and E2 in boys began to increase since 10-11 years old. Serum level of leptin positively correlated with serum level of INS and negatively correlated with serum levels of GH and T, but not correlated with serum level of E2.

CONCLUSIONSLeptin may promote pubertal development of boys, but not the determinant factor in triggering and maintaining their pubertal development. Re-increase in level of leptin during stage G5 could inhibit secretion of GH, and signalize the end of puberty in boys.

Adolescent ; Body Height ; physiology ; Body Mass Index ; Body Weight ; physiology ; Child ; Estradiol ; metabolism ; Growth Hormone ; metabolism ; Humans ; Leptin ; blood ; physiology ; Male ; Puberty ; physiology ; Testosterone ; metabolism

The current epidemic of obesity and its associated metabolic syndromes impose unprecedented challenges to our society. Despite intensive research on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of the leptin neural pathway in the hypothalamus in the regulation of body weight homeostasis. Important hypothalamic neuropeptides have been identified as critical neurotransmitters from leptin-sensitive neurons to mediate leptin action. Recent research advance has significantly expanded the list of neurotransmitters involved in body weight-regulating neural pathways, including fast-acting neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Given the limited knowledge on the leptin neural pathway for body weight homeostasis, understanding the function of neurotransmitters released from key neurons for energy balance regulation is essential for delineating leptin neural pathway and eventually for designing effective therapeutic drugs against the obesity epidemic.
Animals ; Energy Metabolism ; Gene Expression ; Humans ; Hunger ; Hypothalamus ; metabolism ; physiology ; Leptin ; metabolism ; physiology ; Neural Pathways ; metabolism ; Neuropeptides ; genetics ; metabolism ; Obesity ; metabolism

Adipokines, the bioactive factors derived mainly from adipocytes, regulate pancreatic beta-cell function including insulin secretion, gene expression and apoptosis. In this review, we propose that adipokines influence beta-cell function through three interdependent pathways. The first is through regulating lipid and glucose metabolism in beta-cells. The second implicates the change of ion channel opening and closing in beta-cells. The third pathway is via the modification of insulin sensitivity of beta-cells. The endocrine function of adipocytes is dynamic, and the secretion of various adipokines changes under different metabolic conditions. During the progression from the normal state to obesity and to type 2 diabetes, adipokines contribute to the occurrence and development of beta-cell dysfunction in type 2 diabetes.
Adipocytes ; physiology ; Adiponectin ; physiology ; Animals ; Diabetes Mellitus, Type 2 ; physiopathology ; Glucose ; metabolism ; Humans ; Insulin ; pharmacology ; Insulin-Secreting Cells ; physiology ; Leptin ; physiology ; Lipid Metabolism

OBJECTIVESTo study the roles of leptin in the development during puberty in girls and the its relationship with insulin (INS), growth hormone (GH), estradiol (E(2)) and testosterone (T).

METHODSOne hundred and fifty girls with simple obese aged 7 to 17 years, and 150 normal healthy girls and 150 girls with malnutrition matched for age (+/- 3 months) and height (+/- 2 cm) were selected. Serum levels of leptin, INS, GH, E(2) and T were measured for them.

RESULTSTheir serum level of leptin positively correlated with body mass index (BMI) and age. Serum level of leptin in girls increased steadily from Tanner stage B(1) to stage B(5). At Tanner stage B(2), serum level of leptin in the normal groups (7.72 microg/L) was not significantly different from that in those with malnutrition (7.36 microg/L), but significantly lower than that in the obese groups (12.85 microg/L). At other Tanner stages, there was significant difference in serum level of leptin among obese, normal and malnutrition groups. Serum level of leptin correlated negatively with serum GH and positively with serum INS, but not correlated with E(2) and T.

CONCLUSIONSLeptin may play a role in triggering development during puberty in girls. Serum level of leptin at Tanner stage B(2) may be the threshold dose to trigger the onset of puberty in girls. Quickly increasing level of leptin at Tanner stage B(5) may inhibit the increase of GH, which ushered the end of puberty in girls.

Adolescent ; Body Height ; physiology ; Body Mass Index ; Body Weight ; physiology ; Child ; Female ; Growth Hormone ; metabolism ; Humans ; Leptin ; blood ; physiology ; Puberty ; physiology ; Testosterone ; metabolism

In order to investigate the effect of leptin on the secretion of rat pituitary adenoma GH3 cell and its mechanisms, we observed the effect of leptin on the growth hormone secretion, proliferation and apoptosis of GH3 cells. The results indicated that leptin at 1, 10, and 100 nmol/L could inhibit the basal growth hormone secretion of GH3 cells in a dose dependent manner (P<0.05). Short-term treatment of leptin (10 nmol/L) for 30 min, 1 and 3 h did not affect basal GH secretion. However, treatment of the GH3 cells with leptin (10 nmol/L) for 1 d or longer resulted in an inhibition of GH secretion (P<0.05). We used MTT method and flow cytometery (FCM) to study the effect of leptin on the proliferation and apoptosis of GH3 cells. We found that leptin inhibited proliferation of GH3 cells with a dose-dependent manner. And leptin reduced the proportion of cells in S phase, increased the proportion of cells in G1, and increased the proportion of GH3 cells in 2 and 4 phase. These results demonstrate that leptin inhibits the basal GH secretion of GH3 cells, which may be due to the inhibition of DNA synthesis and advanced apoptosis of GH3 cells.
Adenoma ; metabolism ; pathology ; Animals ; Apoptosis ; physiology ; Cell Line, Tumor ; Cell Proliferation ; Growth Hormone ; secretion ; Leptin ; physiology ; Pituitary Neoplasms ; metabolism ; pathology ; Rats

AIMTo explore the effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs, and find out the role leptin plays in acute inflammation.

METHODSA cecal ligation and perforation model of rats was established, setting groups of sham-operation, intralipid injection, injury, estradiol injection and insulin injection. A rat leptin radioimmunoassay was used to check serum leptin concentrations at 12 h after the injury, and RT-PCR was also used to detect leptin mRNA expressions in adipose tissue, lung and liver.

RESULTSCompared with serum leptin level of sham-operation group after injury, that of all the other four groups showed no significant difference, while the level of intralipid group was significantly higher than that of injury group and estradiol group. Compared with leptin mRNA expression level of sham-operation group after injury, that of the other four groups had different changes. Leptin mRNA expression of intralipid group was significantly increased in adipose tissue but decreased in lung and liver.

CONCLUSIONLeptin expression levels may be affected by the changes of energy metabolism and neuroendocrine function after injury, which suggests a possible protective role for leptin in the recovery of body homeostasis.

Animals ; Female ; Inflammation ; metabolism ; Intestinal Perforation ; Leptin ; blood ; physiology ; Ligation ; Male ; Peritonitis ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rabbits ; Rats ; Rats, Sprague-Dawley