Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.
Appetite ; Bile Acids and Salts ; Diet ; Energy Intake ; Energy Metabolism ; Fibroblast Growth Factors ; Gastric Inhibitory Polypeptide ; Ghrelin ; Heme Oxygenase-1 ; Homeostasis* ; Incretins ; Islet Amyloid Polypeptide ; Obesity ; Physiology* ; Weight Loss*

BACKGROUNDObstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides from the same source but have opposite roles. Both of them can affect feeding and regulate vascular tune. The aim of this study was to investigate the relationship between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.

METHODSThis study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group). Polysomnography (PSG) was performed in the OSAS group and over-weight group. Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring. The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSPlasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P < 0.05). Plasma obestatin levels were lower in the over-weight group and OSAS group, but there was no significant difference among the three groups. The blood pressure in OSAS patients was higher, and there was a significant difference in all blood pressure parameters compared to the control group, and in the daytime average diastolic blood pressure (DBP), nocturnal average systolic blood pressure (SBP) and DBP, DBP variability values as compared to over-weight subjects. Furthermore, there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P < 0.01). Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters. In contrast, the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with the blood pressure variability values (P < 0.01). In multivariate analyses, AHI (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were independently related to DBP variability changes.

CONCLUSIONSOur data show plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity. Moreover, the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.

Adolescent ; Adult ; Aged ; Blood Pressure ; physiology ; Circadian Rhythm ; physiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ghrelin ; blood ; Humans ; Male ; Middle Aged ; Obesity ; blood ; physiopathology ; Pancreatic Neoplasms ; blood ; physiopathology ; Prognosis ; Repressor Proteins ; metabolism ; Sleep Apnea, Obstructive ; blood ; physiopathology ; Young Adult

OBJECTIVETo understand adiponectin, leptin, insulin and ghrelin levels in preterm colostrum and mature milk and their influence on the growth and development of the premature infant.

METHODThe study subjects were divided into two groups: preterm group and control group. Specimens of colostrum and mature milk on 42nd day after delivery were collected, the general situation of maternal and infants growth parameters at birth and at postnatal 42 days were recorded. Leptin, adiponectin, insulin and ghrelin levels in colustrum and mature milk were determined and compared.

RESULTA total of 128 mother-infant pairs were involved. There were 128 specimens of colostrums (80 from preterm group, 48 from control group) and 94 specimens of mature milk(50 from premature group, 44 from control group). The levels of colostrum, mature milk adiponectin, leptin, and insulin were not significantly different between the 2 groups; ghrelin levels in colostrum and mature milk of premature group were significantly lower than those in control group (P = 0.038), adiponectin and leptin levels in colostrum were higher than those of the mature milk (P < 0.05), colostrum ghrelin levels were lower than those of mature milk (P < 0.05). Adiponectin, leptin, and ghrelin showed no significant difference between different gestational age groups ( ≤ 34 weeks group vs. > 34 weeks group). True insulin level of mature milk in 34 weeks group was higher than that of > 34 weeks group (29.3 vs. 21.6 mU/L, P = 0.045); true insulin level in colostrums in ≤ 34 weeks group was lower than that in mature milk (21.7 vs. 29.3 mU/L, P = 0.000). Adiponectin levels in colostrum and 42 days weight gain were negatively correlated (r = -0.362, P = 0.025) . Insulin level in mature milk had a negative correlation with birth weight (r = -0.319, P = 0.029) . Ghrelin levels in colostrum and birth weight, length, head circumference, head circumference on 42(nd) day were positively correlated (r = 0.271,0.261,0.360, P < 0.05); weight, length at 42(nd) day and ghrelin levels showed borderline positive correlation (P = 0.050, 0.058).

CONCLUSIONMany bioactive hormones in milk might participate in the regulation of suitable growth after birth. Premature birth affects hormone levels in breast milk. Breast feeding is very important in preterm infants.

Adiponectin ; analysis ; Birth Weight ; physiology ; Breast Feeding ; Colostrum ; chemistry ; Female ; Gestational Age ; Ghrelin ; analysis ; Humans ; Infant ; Infant Nutritional Physiological Phenomena ; Infant, Newborn ; Infant, Premature ; growth & development ; Insulin ; analysis ; Leptin ; analysis ; Male ; Milk, Human ; chemistry ; Weight Gain ; physiology

BACKGROUNDObesity is a common risk factor for several diseases. Obesity related hormone and increased insulin resistance (IR) may contribute to the effects of obstructive sleep apnoea on cardiovascular consequences. We investigated ghrelin and IR in non-diabetic apnoeic patients with stable coronary heart disease and assessed the effects of continuous positive airway pressure (CPAP).

METHODSPlasma ghrelin, glucose and insulin were measured in 22 patients with CPAP and 22 matched controls without CPAP at baseline and three months. Indexes including homeostasis model assessment IR (HOMA IR), HOMA S and HOMA β were calculated for the assessment of IR, insulin sensitivity and pancreatic β cell function.

RESULTSAt three months follow-up, plasma ghrelin levels and HOMA IR in CPAP group were significantly decreased (P=0.002 and 0.046, respectively) while those in control group increased significantly (P=0.012 and 0.009, respectively). Significant moderate correlations were found between ghrelin vs. HOMA IR and ghrelin vs. HOMA S after CPAP, however, for those without CPAP, no significant associations were observed.

CONCLUSIONSShort-term effective continuous positive airway pressure had a significant effect on lowering plasma ghrelin levels and IR, but not body fat. Further large scale and longer term studies are warranted to corroborate these findings.

Blood Glucose ; Case-Control Studies ; Continuous Positive Airway Pressure ; methods ; Coronary Artery Disease ; blood ; Female ; Ghrelin ; blood ; Humans ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; therapy

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-alpha, IFN-gamma, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-alpha, IFN-gamma, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 +/- 19.5 vs 80.9 +/- 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.
Adiponectin/analysis ; Aged ; Antineoplastic Agents/therapeutic use ; Cachexia/*physiopathology ; Colorectal Neoplasms/drug therapy/*metabolism/mortality ; Cytokines/*analysis ; Female ; Follow-Up Studies ; Ghrelin/analysis ; Humans ; Interferon-gamma/analysis/physiology ; Interleukin-6/analysis ; Leptin/analysis ; Lung Neoplasms/drug therapy/*metabolism/mortality ; Male ; Middle Aged ; Peptide Hormones/*analysis ; Prognosis ; Prospective Studies ; Survival Rate ; Tumor Necrosis Factor-alpha/analysis ; Weight Gain ; Weight Loss

The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were intragastrically administered with diltiazem solution (daily 16 mg/kg, 30 mg/kg or 80 mg/kg, 30 d), and the rats with saline as control. To detect the effects of diltiazem on food intake and body weight, the average daily food intake and body weight were recorded, and the serum metabolic hormones of plasma growth hormone (GH) and neuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometer and the modified Mett's method, the effects of diltiazem on rat's gastrointestinal function and pepsin activity were tested, respectively. In addition, the gastric juice's acidity of rats was detected by titration and the secretion amount was calculated. The results showed that the food intake and body weight were maximally promoted by diltiazem at the dose of 30 mg/kg daily (30 d). The average daily food intake and body weight were significantly increased, and the serum concentrations of GH and NPY were also remarkably increased in diltiazem-treated groups compared with those in control group. The results also showed that the gastric emptying rate, gastric acid secretion and the activity of pepsin were significantly increased in diltiazem-treated group compared with those in control group. These results suggest that diltiazem induces enhancement of eating, in the same time, it can also stimulate the gastrointestinal function and regulate growth of rat.
Animals ; Body Weight ; drug effects ; Diltiazem ; pharmacology ; Eating ; drug effects ; Female ; Gastric Emptying ; drug effects ; Gastrointestinal Motility ; drug effects ; Gastrointestinal Tract ; physiology ; Growth Hormone ; blood ; Neuropeptide Y ; blood ; Rats ; Rats, Sprague-Dawley ; Receptors, Ghrelin ; agonists

The brain-gut peptide ghrelin, a endogenous ligand for the growth hormone secretagogue hormone receptor, is mainly produced by gastric cells in the periphery, regulating energy metabolism via stimulating the appetite. Inside the brain, ghrelin is mainly expressed in the pituitary and in the hypothalamic arcuate nucleus, regulating the synthesis and secretion of neuropeptides that are correlated with feeding behavior, reproduction, and stress responses. Recently, more and more researches focused on the regulating roles of ghrelin on learning and memory, and mood regulation have indicated that ghrelin may inhibit neuronal apoptosis, improve cognitive function, and regulate the activities of neuroendocrine systems such as the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis thus get involved in the pathogenesis of neuropsychiatric diseases. The aim of this review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin in the brain.
Apoptosis ; Brain ; metabolism ; pathology ; physiology ; Ghrelin ; metabolism ; physiology ; Humans ; Learning ; Memory ; Neurons ; pathology ; Parkinson Disease ; metabolism ; pathology ; physiopathology

OBJECTIVETo investigate the effect of growth hormone secretagogue(ghrelin) on the contraction and relaxation of small intestinal smooth muscle in rats and its mechanism.

METHODSTwenty-four vagotomized rats were injected intraperitoneally with different concentrations of ghrelin (0, 20, 40, 80 μg/kg). The small intestinal transit were observed. The effect of ghrelin(0.01, 0.1, 0.5, 1.0 μmol/L) on the contraction and relaxation of rat small intestinal smooth muscle strips was observed in vitro in the presence of carbachol(50 nmol/L), the locations of ghrelin receptors(GHS-R1a) on different cells in small intestinal muscle layers were detected by immunofluorescence.

RESULTSWith the increase of concentrations, ghrelin elevated the percentage of small intestinal transit[(25.4±1.0)%, (33.7±1.9)%, (39.3±2.4)%, (44.7±2.1)%] in a dose-dependent manner, and the differences were statistically significant among groups(P<0.05). Ghrelin could also enhance the contraction [(67.0±2.4)%,(149.5±3.3)%, (187.1±4.7)%, (213.5±3.4)%] and relaxation[(35.3±1.1)%, (62.9±3.8)%, (79.6±2.7)%, (94.6±2.2)%] of smooth muscle strips mediated by Cch in a dose-dependent manner, and the differences were statistically significant among groups(P<0.05). Immunofluorescence revealed that ghrelin receptors mainly located on membrane of the nerve cells in the muscle layers, while no receptors were observed on membrane of the smooth muscle cells.

CONCLUSIONGhrelin may enhance the effect of the contraction and relaxation of the rat small intestinal smooth muscle mediated by cholinergic neurotransmitters by activating the nerve cells in the enteric plexus.

Animals ; Gastrointestinal Motility ; Ghrelin ; pharmacology ; Intestine, Small ; drug effects ; physiology ; Male ; Muscle Contraction ; drug effects ; physiology ; Muscle, Smooth ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of the expression of ghrelin receptors on the postoperative small intestine dysmotility in rat models.

METHODSThe effect of different concentrations of ghrelin (0, 0.01, 0.1, 0.5, 1.0 μmol/L) on the contraction of smooth muscle strips of rat small intestine in the presence or absence of carbachol was observed in vitro. End-to-side anastomosis was performed in the study group and sham controls were used. The expression of ghrelin receptors(GHS-R1a) in small intestine muscle layers was detected by immunohistochemistry and Western blot.

RESULTSIn vitro, ghrelin enhanced the contraction of smooth muscle strips in the presence of carbachol, and the differences in contraction induced by different concentrations of ghrelin(0.1, 0.5, 1.0 μmol/L) were statistically significant [(223±18)%, (245±22)%, (264±25)%, P<0.01]. Immunohistochemistry study showed that GHS-R1a mainly located in the muscular layer of the bowel wall. The expression of GHS-R1a in the circular and longitudinal muscle was significantly weaker than that in the control group. The expression of ghrelin receptors after surgery was down-regulated in the study group, which was lower than that in the control group(0.51±0.02 vs. 0.71±0.01, P<0.01).

CONCLUSIONDown regulation of ghrelin receptors in small intestine muscle layers may contribute to the occurrence of small intestine dysmotility after intestinal surgery.

Animals ; Down-Regulation ; Gastrointestinal Motility ; drug effects ; physiology ; Ghrelin ; pharmacology ; Intestine, Small ; drug effects ; metabolism ; physiology ; surgery ; Male ; Postoperative Period ; Rats ; Rats, Sprague-Dawley ; Receptors, Ghrelin ; metabolism

BACKGROUNDCyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons. Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities. The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.

METHODSTwelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured. Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction.

RESULTSFour weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ± 15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12) mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P < 0.05). Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P = 0.004), and the plasma IGF-1 level was significantly lower than control (P = 0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P = 0.000), and the expression of IGF-1 mRNAs was elevated (P = 0.001).

CONCLUSIONSChronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and myocardial ghrelin mRNA expression were down-regulated in the chronic cyanotic immature piglets. The ghrelin system may be an important part of the network regulating cardiac performance.

Animals ; Cyanosis ; blood ; metabolism ; physiopathology ; Female ; Ghrelin ; blood ; metabolism ; Heart Defects, Congenital ; blood ; metabolism ; physiopathology ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Pulmonary Circulation ; physiology ; Swine