Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells (HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. The secretion of pro-inflammatory cytokines (human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay (ELISA). The expression of pro-angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Relevant molecules of the nuclear factor-κB (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs (HPMSCs/ leptin) exhibited better cell proliferation, migration, and angiogenic potential (expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines (human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.
Cell Proliferation ; Cells, Cultured ; Cytokines/biosynthesis* ; Female ; Human Umbilical Vein Endothelial Cells/radiation effects* ; Humans ; Inflammation/etiology* ; Leptin/pharmacology* ; Mesenchymal Stem Cells/physiology* ; Neovascularization, Physiologic/physiology* ; Placenta/cytology* ; Pregnancy ; STAT3 Transcription Factor/genetics* ; Transcription Factor RelA/genetics* ; X-Rays

Leptin, an adipocyte-derived hormone, serves numerous physiological functions in the body, particularly during puberty and reproduction. The exact mechanism by which leptin activates the gonadotropin-releasing hormone (GnRH) neurons to trigger puberty and reproduction remains unclear. Given the widespread distribution of leptin receptors in the body, both central and peripheral mechanisms involving the hypothalamic-pituitary-gonadal axis have been hypothesized. Leptin is necessary for normal reproductive function, but when present in excess, it can have detrimental effects on the male reproductive system. Human and animal studies point to leptin as a link between infertility and obesity, a suggestion that is corroborated by findings of low sperm count, increased sperm abnormalities, oxidative stress, and increased leptin levels in obese men. In addition, daily leptin administration to normal-weight rats has been shown to result in similar abnormalities in sperm parameters. The major pathways causing these abnormalities remain unidentified; however, these adverse effects have been attributed to leptin-induced increased oxidative stress because they are prevented by concurrently administering melatonin. Studies on leptin and its impact on sperm function are highly relevant in understanding and managing male infertility, particularly in overweight and obese men.
Animals ; Humans ; Infertility, Male/physiopathology* ; Leptin/physiology* ; Male ; Obesity/complications* ; Overweight/complications* ; Reproduction/physiology*

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.
Animals ; Diet, High-Fat ; adverse effects ; Inflammation ; chemically induced ; metabolism ; Leptin ; metabolism ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Nociception ; drug effects ; physiology ; Nociceptive Pain ; etiology ; metabolism ; Obesity ; complications ; metabolism ; Pain Measurement ; Pain Threshold ; drug effects ; physiology ; Receptors, Leptin ; metabolism ; Signal Transduction ; drug effects ; physiology

BACKGROUNDObesity has an adverse effect on iron status. Hepcidin-mediated inhibition of iron absorption in the duodenum is a potential mechanism. Iron-deficient obese patients have diminished response to oral iron therapy. This study was designed to assess whether acupuncture could promote the efficacy of oral iron supplementation for the treatment of obesity-related iron deficiency (ID).

METHODSSixty ID or ID anemia (IDA) patients with obesity were screened at Beijing Hospital of Traditional Chinese Medicine and were randomly allocated to receive either oral iron replacement allied with acupuncture weight loss treatment (acupuncture group, n = 30) or oral iron combined with sham-acupuncture treatment (control group, n = 30). Anthropometric parameters were measured and blood samples were tested pre- and post-treatment. Differences in the treatment outcomes of ID/IDA were compared between the two groups.

RESULTSAfter 8 weeks of acupuncture treatment, there was a significant decrease in body weight, body mass index, waist circumference, and waist/hip circumference ratio of patients in the acupuncture group, while no significant changes were observed in the control group. Oral iron supplementation brought more obvious improvements of iron status indicators including absolute increases in serum iron (11.08 ± 2.19 μmol/L vs. 4.43 ± 0.47 μmol/L), transferrin saturation (11.26 ± 1.65% vs. 1.01 ± 0.23%), and hemoglobin (31.47 ± 1.19 g/L vs. 21.00 ± 2.69 g/L) in the acupuncture group than control group (all P < 0.05). Meanwhile, serum leptin (2.26 ± 0.45 ng/ml vs. 8.13 ± 0.55 ng/ml, P < 0.05) and hepcidin (3.52 ± 1.23 ng/ml vs. 6.77 ± 0.84 ng/ml, P < 0.05) concentrations declined significantly in the acupuncture group than those in the control group.

CONCLUSIONAcupuncture-based weight loss can enhance the therapeutic effects of iron replacement therapy for obesity-related ID/IDA through improving intestinal iron absorption, probably by downregulating the systemic leptin-hepcidin levels.

Acupuncture Therapy ; Adult ; Female ; Hepcidins ; blood ; Humans ; Intestinal Absorption ; physiology ; Iron ; deficiency ; metabolism ; Leptin ; blood ; Male ; Middle Aged ; Obesity ; blood ; metabolism ; therapy ; Young Adult

Lithium is the first line treatment for maintenance treatment of bipolar disorder. Among the long term adverse effects, weight gain is likely to affect a subset of patients. There is no specific guideline for the treatment of lithium-induced weight gain. We report a young male with bipolar disorder who had significant weight gain with lithium (25 kg), which responded to metformin treatment at 500 mg twice daily. The proposed mechanism of weight lowering effect of metformin includes changes in hypo-thalamic physiology, including leptin and insulin sensitivity, as well as circadian rhythm changes affecting food intake, regulation of fat oxidation and storage in liver, skeletal muscle, and adipose tissue.
Adipose Tissue ; Bipolar Disorder ; Circadian Rhythm ; Eating ; Humans ; Insulin Resistance ; Leptin ; Lithium ; Liver ; Male ; Metformin* ; Muscle, Skeletal ; Physiology ; Weight Gain*

This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.
Asthma ; complications ; Humans ; Leptin ; physiology ; Nerve Growth Factor ; physiology ; Neurotransmitter Agents ; physiology ; Obesity ; etiology ; Plasminogen Activator Inhibitor 1 ; physiology

OBJECTIVEConditioned taste preference (CTP) is a taste learning reflex by which an animal learns to prefer a substance which tastes not well and has been studied with much interest in recent years. However, the neural substrates of CTP are less known. This study aimed to determine the possible neural path- ways of CTP and whether serum leptin level and the leptin receptor (OB-Rb) in the hind brain are involved following CTP formation.

METHODSWe established CTP of quinine in rats with a 2-bottle preference test. The serum leptin concentrations were detected, the expression of c-fos in the rat brain was tested to determine the nuclei in relation with establishment of CTR Finally, the OB-Rb mRNA expression was examined by RT-qPCR assay in parabrachial nucleus (PBN) and the nucleus of the solitary tract (NST) of the hind brain.

RESULTSCompared with control group, the level of serum leptin was higher in the CTP group (4.58 ± 0.52 vs 1.67 ± 0.25 µg/L, P < 0.01); increased c-fos positive cells were found in the anterior hypothalamus (AH, 221.75 ± 4.96 vs. 178.50 ± 6.63 cells/mm², P < 0.05), the basal lateral amygdala (BLA, 70.75 ± 6.17 vs 56.50 ± 3.62 cells/ mm², P < 0.05) and the nucleus of the solitary tract (NST, 41.25 ± 1.32 vs 32.50 ± 1.02 cells/mm², P < 0.05). But in ventromedial nucleus of the hypothalamus (VMH, 20.75 ± 2.73 vs 38.5 ± 1.54 per 1 mm², P < 005), PBN (21.50 ± 2.24 vs 36.25 ± 1.49 cells/mm², P < 0.05) and the central nucleus of the amygdala (CeA, 22.25 ± 1.53 vs 35.50 ± 2.11 cells/mm², P < 0.05), the number of c-fos positive cells was decreased in the CTP group. In addition, we found OB-Rb mRNA expression in PBN of CTP group rats was higher than that of control group (0.95 ± 0.055 vs 0.57 ± 0.034, P < 0.05), while there was no significant difference of OB-Rb mRNA expression in NST between the two groups.

CONCLUSIONNuclei AH, BLA, NST, VMH, PBN and CeA participate in the formation of CTP. Leptin and its receptor in PBN may be involved in the formation and maintenance of CTP.

Animals ; Conditioning (Psychology) ; Leptin ; blood ; Rats ; Receptors, Leptin ; physiology ; Rhombencephalon ; physiology ; Taste ; physiology

Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance.
Adipose Tissue ; Cardiovascular Diseases ; Humans ; Hypertension ; Hypertrophy, Left Ventricular ; Insulin Resistance ; Leptin ; physiology ; Receptors, Leptin ; Renin-Angiotensin System ; Sympathetic Nervous System

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

OBJECTIVETo investigate the effect of immunization with prokaryotically expressed recombinant fusion protein of extracellular near-transmembrane domain of Tibet minipig leptin receptor (OBR) on fat deposition in SD rats.

METHODSA pair of specific primers containing BamHI and HindIII restriction enzyme sites was designed to amplify the extracellular near-transmembrane domain (1705-2364 bp) of Tibet minipig OBR gene. After digestion, the amplified fragment was inserted into the plasmid pRSETA between BamHI and HindIII sites. The recombinant plasmid was transformed and expressed in E.coli BL21(DE3) and the product was analyzed by SDS-PAGE and Western blotting. SD rats were immunized with the fusion protein, and the changes in body weight, feed intake, body length, Lee's index, percentage of abdominal fat, liver fat deposition and subcutaneous fat deposition were assessed.

RESULTSThe recombinant fusion protein obtained (about 27.6 kD) was expressed in E.coli induced by IPTG and identified by SDS-PAGE and Western blotting. The rats immunized with the fusion protein showed no significant changes in body weight, body length, Lee's index, percentage of abdominal fat or liver fat deposition as compared with the control rats. Nevertheless, the immunization caused significantly increased feed intake and significantly decreased volume of subcutaneous fat cells.

CONCLUSIONImmunization with the fusion protein of extracellular near-transmembrane domain of Tibet minipig OBR can promote feed intake and suppress subcutaneous fat deposition in SD rats.

Adiposity ; drug effects ; Animals ; Base Sequence ; Female ; Gene Expression ; Genetic Vectors ; Obesity ; Plasmids ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; administration & dosage ; genetics ; Recombinant Fusion Proteins ; administration & dosage ; genetics ; Subcutaneous Fat ; physiology ; Swine ; Swine, Miniature