leptin and Spinal-Cord-Injuries

Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker changes in this elevated risk group. We focused specifically on the endocrine and inflammation profile differences between SCI and able-bodied individuals (ABI). Our aim was to determine the differences in inflammatory markers and endocrine profiles between SCI and ABI. We systematically searched 4 electronic databases for relevant studies. Human observational (cross-sectional, cohort, case-control) studies that compared biomarkers of interest between SCI and ABI population were included. Weighted mean difference between SCI and ABI was calculated using random-effects models. Heterogeneity was computed using I

Topics: Biomarkers; C-Reactive Protein; Creatinine; Cross-Sectional Studies; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Spinal Cord Injuries; Testosterone

The aim of this study was to investigate changes of leptin concentration in plasma in patients with spinal cord injury to come to a single concept by using a Meta-analysis.. Systematic Review.. Searching relevant articles was performed in Ovid data base, Medline (PubMed) EMBASE, Google Scholar, Cochrane and Scopus up to February 2013. Five articles were selected using two independent reviewers. Analysis were performed using SPSS version 18 and Comparative Meta-analysis software version 2.0.. The combined analysis with confidence interval of 95% using comprehensive meta-analysis showed significant higher leptin levels in patients with spinal cord injury in comparison with able bodies (P<0.0001). The effect of spinal lesion level on plasma leptin concentration was also statistically significant (P<0.0001). Body mass index was positively related to plasma leptin concentration in both groups (P<0.0001).. This Meta analysis approves increased level of leptin in spinal cord injured patients which can be due to fat distribution changes and sympathetic dysfunction in these patients. Our results also showed that patients with higher spinal lesion level have higher plasma leptin concentration.

Topics: Biomarkers; Body Mass Index; Embolism, Fat; Humans; Leptin; Predictive Value of Tests; Spinal Cord Injuries

The present study was designed to compare the body composition and indicators of chronic inflammatory grade, such as leptin, adiponectin, and resistin concentrations in irregularly active and active SCI subjects. Thirty-two male subjects participated in this study. They were divided into three groups: able-bodied control irregularly active (control,

Topics: Adult; Exercise; Humans; Leptin; Linear Models; Spinal Cord Injuries

Omega-3 fatty acids have been recently proposed to induce neural improvement in patients with spinal cord injury (SCI) while affecting some hormones including leptin and adiponectin.. We tried to evaluate the effect of omega-3 fatty acids on circulatory concentrations of leptin and adiponectin among these patients.. This study is a double-blinded randomized clinical trial with intervention duration of 14 months.. A tertiary rehabilitation center.. Total of 104 patients with SCI who did not meet our exclusion criteria entered the study. Those with history of diabetes, cancer, endocrinology disease, acute infection, and use of special medications were excluded. Patients were divided randomly into the treatment and control group by using permuted balanced block randomization.. The treatment group received two MorDHA® capsules per day (each capsule contain 465 mg of docosahexaenoic acid (DHA) and 63 mg of eicosapentaenoic acid (EPA)) for 14 months while the control group received placebo capsules with similar color, shape, and taste.. Leptin and adiponectin concentrations in plasma were measured at the beginning of trial and then after 6 and 14 months.. Fourteen months of treatment with DHA and EPA did not influence concentrations of leptin but adiponectin level was significantly decreased (P: 0.03). Weight was positively correlated with leptin level at stage 0 of trial (P: 0.008, r=0.41) while this association was attenuated through stages of trial after intervention.. Our data show that omega-3 fatty acids may not affect plasma concentrations of leptin but adiponectin level is decreased in patients with SCI. Moreover, this intervention influences the linear relationship between weight and leptin after 14 months administration of DHA and EPA.

Topics: Adiponectin; Adolescent; Adult; Aged; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Female; Humans; Leptin; Male; Middle Aged; Spinal Cord Injuries; Treatment Outcome; Young Adult

To ascertain the effect of arm cranking exercise on improving plasma levels of inflammatory cytokines and adipokines in untrained adults with chronic spinal cord injury (SCI).. Longitudinal study.. Community-based supervised intervention.. Men (N=17) with complete SCI at or below T5 volunteered for this study. Participants were randomly allocated to the intervention (n=9) or control group (n=8) using a concealed method.. A 12-week arm cranking exercise program of 3 sessions per week consisted of warm-up (10-15min), arm crank (20-30min; increasing 2min and 30s every 3wk) at a moderate work intensity of 50% to 65% of heart rate reserve (starting at 50% and increasing 5% every 3wk), and cool-down (5-10min).. Plasma levels of leptin, adiponectin, plasminogen activator inhibitor-1, tumor necrosis factor-alpha, and interleukin-6 were determined. Furthermore, physical fitness (maximum oxygen consumption [V˙O2max]) and body composition (anthropometric index, waist circumference, and body mass index) were also assessed.. Plasma levels of leptin, tumor necrosis factor-alpha, and interleukin-6 were significantly decreased after the completion of the training program. Similarly, the anthropometric index and waist circumference were diminished too. A moderate correlation was found between leptin and the anthropometric index. Finally, V˙O2max was significantly increased, suggesting an improvement of physical fitness in the intervention group. No changes were found in the control group.. Arm cranking exercise improved low-grade systemic inflammation by decreasing plasma levels of inflammatory cytokines. Furthermore, it also reduced plasma leptin levels. Long-term, well-conducted studies are still required to determine whether these changes may improve clinical outcomes of adults with chronic SCI.

Topics: Adiponectin; Adult; Anthropometry; Arm; Exercise Therapy; Humans; Inflammation; Interleukin-6; Leptin; Longitudinal Studies; Male; Oxygen Consumption; Plasminogen Activator Inhibitor 1; Spinal Cord Injuries; Treatment Outcome; Tumor Necrosis Factor-alpha

To determine the acute effect of neurological lesion on body composition, plasma leptin level, and the lipid profile, 7 male patients with acute and complete spinal cord injury (SCI) and 9 able-bodied (AB) males were investigated. At 16, 24, 36, and 48 weeks after injury, plasma leptin level and the lipid profile were analyzed, while whole body (WB) and regional fat mass (FM) and fat-free soft tissue (FFST) were measured by dual-energy x-ray absorptiometry (DXA). At all stages, despite no difference being found between both groups for body mass index (BMI), SCI patients had higher FM at WB (P < .01), lower (P < .01), and upper limbs (P < .05), while FFST was lower at WB (P < .05) and lower limbs (P < .01). The leptin level increased gradually from week 24 and was higher at weeks 16, 36, and 48 in SCI patients than in AB patients (7.0 +/- 3.9; 9.7 +/- 5.1; 10.6 +/- 5.3, respectively, v 3.5 +/- 2.5 ng. mL(-1)). SCI patients had lower high-density lipoprotein-cholesterol (HDL-C) (P < .05) and apolipoprotein (apo) A1 (P < .01), while no difference was found for total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), or ApoB levels. At all stages, leptin was strongly and positively correlated with WB and regional FM % (r > 0.75; P < .05) and with TC, LDL-C, and ApoB levels (r > 0.65; P < .05). Leptin was negatively correlated with FFST and the ApoA1/ApoB ratio (r > -0.75; P < .05). In conclusion, neurological lesion induced an early and acute alteration in body composition and lipid profile. The strong relationship between serum leptin and FM suggests that this hormone can be used as a surrogate marker of FM in acute SCI patients and thus would serve as a good indicator for cardiovascular disease risk.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Biomarkers; Body Composition; Body Mass Index; Hormones; Humans; Leptin; Lipids; Longitudinal Studies; Male; Radioimmunoassay; Spinal Cord Injuries

Cross-sectional study.. To assess associations between weekly aerobic exercise minutes and resting interleukin-6 (IL-6), C-reactive protein (CRP), or leptin levels in adults with chronic spinal cord injury (SCI).. Three hundred and forty-four community-dwelling men and women with SCI duration of > 1 year.. CRP, IL-6, and leptin levels were quantified by ultra-sensitive enzyme-linked immunoassay. Smoking, medication use, comorbidities, and aerobic exercise minutes per week were assessed by self-reported questionnaire. Body composition was determined by whole-body dual-energy X-ray absorptiometry. Generalized linear models were used to assess associations.. In multivariable modeling, resting IL-6 levels were 0.001 pg/mL lower for every 1 min of weekly aerobic exercise. IL-6 levels increased with increasing android-to-gynoid fat ratio, in active/ever smokers compared to never smokers, and in individuals with skin pressure injuries compared to those without. IL-6 levels were lower in active ibuprofen users compared to nonusers. We found no association between weekly exercise minutes and CRP or leptin when designing similar models.. Increasing aerobic exercise minutes is associated with lower IL-6 levels in adults with chronic SCI when considering body composition, smoking, skin pressure injuries, and ibuprofen use. CRP and leptin did not demonstrate an association with exercise when considering the similar variables. The use of these biomarkers in assessing the therapeutic value of future exercise-related interventions will be paramount for meaningful health improvement among those with SCI. Although a large, prospective dataset, this cross-sectional study cannot assign causation. Future prospective studies are needed to confirm these findings.

Topics: Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Exercise; Female; Humans; Ibuprofen; Interleukin-6; Leptin; Male; Spinal Cord Injuries

To investigate the use of surrogate plasma fatty acid analysis to provide further insights into the underlying adiposity and the development of metabolic syndrome in men with spinal cord injury (SCI).. Case-control, cross-sectional study.. Community-based individuals with spinal cord injury and healthy controls.. Twenty men with SCI age, height and weight matched with 20 able-bodied controls.. Lean tissue (LTM) and fat mass (FM) were determined using dual energy X-ray absorptiometry. Fasting blood samples were taken for analysis of fatty acids, adiponectin, insulin, glucose and leptin. Enzymatic indices were calculated using relevant fatty acids.. Total FM, leptin, stearoyl coenzyme A desaturase (SCD) Δ9 (SCD-16, 16:1/16:0, and SCD-18, 18:1/18:0) indices and Δ6 desaturase index were significantly higher (P < 0.05) in the SCI group than the controls. Significant differences between the groups was observed for several individual fatty acids. Correlational analysis revealed a different pattern between blood biomarkers and indices of SCDs, de novo lipogenesis and elongase. Associations between the desaturase and elongase indices and biomarkers in the controls followed those reported elsewhere for able bodied participants; the same associations were not observed in the SCI group.. We have identified disturbances in fatty acid biosynthesis in SCI individuals likely associated with the development of adipose tissue below the lesion and a decrease in LTM. Loss of LTM may disturb the normal skeletal muscle-fatty acid metabolic processes leading to the disruption of metabolic homeostasis, previously identified in persons with SCI.

Topics: Adiponectin; Adiposity; Adolescent; Adult; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Fatty Acid Desaturases; Fatty Acid Elongases; Fatty Acids; Humans; Insulin; Leptin; Male; Middle Aged; Spinal Cord Injuries; Young Adult

To investigate the relationship of carotid artery intima-media thickness (IMT) and cardiac structure and function with adipocytokines in sedentary (S-SCI) and physically active (PA-SCI) subjects with spinal cord injury (SCI).. Cross-sectional observational study.. Academic medical center.. Men with chronic (>1y) SCI (N=41; 16 S-SCI, 25 PA-SCI) were evaluated. S-SCI subjects did not perform labor that required physical effort, recreational physical activity, or sports, while PA-SCI subjects included competing athletes who were regularly performing adapted sports.. Not applicable.. Clinical, laboratory, carotid ultrasonography, and echocardiography analysis. Plasma leptin, adiponectin, and plasminogen activating inhibitor-1 (PAI-1) levels were determined.. PA-SCI subjects had similar levels of adipocytokines, but lower carotid IMT and carotid IMT/diameter, and better left ventricular diastolic function than S-SCI participants. Bivariate analysis showed that adiponectin was inversely correlated with triglycerides (r=-.85, P<.001), low-density lipoprotein cholesterol (r=-.57, P<.05), and carotid IMT/diameter (r=-.56, P<.05) in S-SCI but not in PA-SCI participants. Additionally, the leptin-adiponectin ratio showed a direct correlation with triglycerides (r=.84, P<.001) and low-density lipoprotein cholesterol (r=.53, P<.05) in S-SCI but not in PA-SCI individuals. By contrast, the studied adipocytokines did not correlate with cardiac structure and function in PA-SCI and S-SCI participants.. Lower adiponectin levels and higher leptin-adiponectin ratio are related to adverse vascular and/or metabolic characteristics in individuals with SCI. This relationship, however, appears to be mitigated by regular physical activity.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Cross-Sectional Studies; Echocardiography; Enzyme-Linked Immunosorbent Assay; Exercise; Heart Function Tests; Humans; Leptin; Male; Plasminogen; Spinal Cord Injuries; Ultrasonography

Leptin is an adipo-myokine that regulates appetite and energy expenditure by a neuroendocrine feedback loop. Leptin levels are positively correlated with BMI in the spinal cord injury population and leptin levels are greater in individuals with spinal cord injury compared to uninjured controls. Leptin is produced in multiple tissues, including fat, bone, and skeletal muscle and is a putative biomarker of sedentary behavior in older adults. We assessed body composition leptin, adiponectin, and IL-6 levels in 205 men with chronic spinal cord injury. We found no association between age, injury duration, injury level, injury completeness, or walking status and leptin. There was a significant positive association between lean mass and leptin in men with SCI that was independent of fat. Adjusting for body composition, leptin levels were positively associated with IL-6 and negatively associated with adiponectin levels. When considering men with SCI and sarcopenic obesity, only fat mass remained positively associated with leptin. We found no association between IL-6, adiponectin, or lean mass and leptin in the sarcopenic obesity group. Our findings suggest that lean mass is an under recognized, but substantial, source of circulating leptin. Furthermore, SCI-related sarcopenic obesity may result in dysregulated adipo-myokine metabolism with local and systemic physiologic effects.

Topics: Adult; Aged; Aged, 80 and over; Body Composition; Chronic Disease; Humans; Leptin; Male; Middle Aged; Spinal Cord Injuries; Young Adult

Spinal cord injury (SCI) causes long-term disability and has no effective clinical treatment. After SCI, extracellular adenosine triphosphate (ATP) leads to an influx of extracellular Ca

Topics: Animals; Apoptosis; Calcium; Caveolin 1; Dose-Response Relationship, Drug; Gene Expression Profiling; Injections, Intraperitoneal; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neurons; Protective Agents; Spinal Cord Injuries; Structure-Activity Relationship

C-reactive protein (CRP) has been shown to correlate with health-related quality of life (HRQL) in some chronic medical conditions. However, these associations have not yet described in spinal cord injury (SCI). In this study, we tried to identify biomarkers associated with HRQL in SCI.. Cross-sectional.. Tertiary rehabilitation center.. Referred patients to Brain and Spinal Cord Injury Research Center between November 2010 and April 2013.. Blood samples were taken to measure circulatory CRP, leptin, adiponectin, ferritin, parathyroid hormone, calcitonin, thyroid hormones, fasting plasma glucose and lipid profile. All the analyses were performed with adjustment for injury-related confounders (level of injury, injury completeness and time since injury) and demographic characteristics. HRQL was measured with Short Form health survey (SF-36).. The initial inverse association between CRP and total score of SF-36 (P: 0.006, r = -0.28) was lost after adjustment for confounders. However, the negative correlation between CRP and Mental Component Summary (MCS) remained significant (P: 0.0005, r = -0.38). Leptin level was inversely correlated with Physical Component Summary (PCS) (P: 0.02, r = -0.30).. Although CRP and leptin levels were not related with total scores of SF-36 questionnaire, CRP can be more useful in determining mental component of HRQL whereas leptin can be a determinant of physical component. The combined consideration of these two biomarkers may help to predict HRQL in individuals with SCI.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Female; Humans; Leptin; Male; Mental Health; Middle Aged; Quality of Life; Spinal Cord Injuries

Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2. Leptin, a glycoprotein, induces the activation of the Janus kinase (JAK2)/signal transducers and activators of transcription-3 (Stat3) pathway via the leptin receptor. In this study, we found that 1) prolonged leptin treatment suppressed the ATP-stimulated release of AA and PGE2 from cultured spinal cord astrocytes; 2) leptin elevated the expression of caveolin-1 (Cav-1) via the JAK2/Stat3 signaling pathway; 3) Cav-1 blocked the interaction between Src and EGFR, thereby inhibiting the phosphorylation of EGFR and cPLA2 and attenuating the release of AA or PGE2; 4) pretreatment with leptin decreased ;he level of apoptosis and the release of interleukin-6 from cocultured neurons and astrocytes; and 5) leptin improved the recovery of locomotion in mice after SCI. Our results highlight leptin as a promising therapeutic agent for SCI. © 2016 Wiley Periodicals, Inc.

Topics: Adenosine Triphosphate; Animals; Astrocytes; Calcium-Binding Proteins; Caveolin 1; Cells, Cultured; Culture; Disease Models, Animal; ErbB Receptors; Leptin; Mice; Mice, Inbred C57BL; Microfilament Proteins; Motor Activity; Nerve Tissue Proteins; Neurons; Receptors, Leptin; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Up-Regulation

Previously, the associations between leptin and adiponectin levels with bone mineral density (BMD) have been reported in different populations, and occasionally, controversial results have been demonstrated. Until now, these relationships in spinal cord-injured individuals have not yet been described.. We tried to investigate the correlation between leptin and adiponectin concentrations in plasma and BMD in Iranian patients with spinal cord injury (SCI).. Cross-sectional investigation.. Referred patients with SCI who did not meet our exclusion criteria such as pregnancy, lactation, amputation, history of diabetes, cancer, endocrinology disease, and use of special medications entered the study.. Bone mineral density of femoral neck, trochanter, intertrochanteric zone, total hip, and lumbar vertebrae assessed by dual-energy X-ray absorptiometry and serum leptin and adiponectin levels measured by blood sample analysis using immunoassay techniques.. Patient demographic characteristics were measured during face-to-face visits. Injury level and Spinal cord Injury Association (ASIA) score were assessed by clinical examination and were confirmed by imaging aids. Measured levels of leptin and adiponectin and dual-energy X-ray absorptiometry results were analyzed with partial correlation analysis method after adjustment for weight, body mass index (BMI), and age.. Total of 104 patients (19 females and 85 males) entered this investigation. Higher leptin concentration was significantly associated with higher BMD in femoral neck (p=.006, r=0.73), femoral intertrochanteric zone (p=.001, r=0.83), and hip (p=.001, r=0.81) only in female patients, whereas no such association was detected in male participants after adjusting for BMI and age. Leptin and adiponectin levels were not associated with lumbar spine BMD in both genders. Neither injury level nor ASIA score and plegia type (paraplegia or tetraplegia) influenced on leptin and adiponectin concentrations.. We found no association between leptin concentration and BMD in male individuals, whereas a positive correlation between leptin and BMD of femoral neck, intertrochanter, and hip was observed in female patients that shows a sexual polymorphism in this relationship. However, by considering the low number of female participants, these results should be interpreted cautiously. Lumbar spine BMD was associated with neither leptin nor adiponectin level in both genders.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Aged; Body Mass Index; Body Weight; Bone Density; Cross-Sectional Studies; Female; Femur; Hip Joint; Humans; Iran; Leptin; Lumbar Vertebrae; Male; Middle Aged; Pregnancy; Spinal Cord Injuries

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

Topics: Adult; Biomarkers; Bone Density; Femoral Fractures; Fracture Healing; Fractures, Bone; Humans; Leptin; Male; Middle Aged; Spinal Cord Injuries; Spine; Tibial Fractures; Young Adult

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone-fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose-derived adiponectin may contribute to SCI-induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Biomarkers; Bone Density; Bones of Lower Extremity; Humans; Leptin; Male; Middle Aged; Osteoporosis; Osteoporotic Fractures; Spinal Cord Injuries; Walking; Wheelchairs

Physical exercise has an important role in reducing body fat, risk of chronic disease and systemic inflammation. The aim of this study was to determine serum leptin and insulin concentrations and their relationship to the time of physical exercise after injury in men with cervical spinal cord injury (c-SCI).. c-SCI subjects with lesion level in C5-C7 (n=25) were divided into two groups: physically active (PA, n=13; those who practiced physical exercise for at least 3 months, three times per week or more, for a total minimum of 150 min of physical activity per week) and non-physically active (N-PA, n=9). Body composition was assessed by dual energy X-ray absorptiometry. Blood samples were obtained 12 h after an overnight fast to measure insulin and leptin in serum, and glucose and C-reactive protein (CRP) in plasma, by validated methods.. Comparing the PA and N-PA group, the first presented lower: total body mass (-13%), body mass index (-16%), fat mass (kg -39%, FM% -30%), CRP (-23%), serum insulin (-61%), homeostasis model assessment (HOMA, -35%) and serum leptin (-62%; P<0.05). Both serum insulin (r=-0.561; P<0.05) and HOMA (r=-0.591; P<005) were inversely proportional to the time of practice of physical activity after injury.. Our results suggest that exercise was able to reduce fat mass and increase insulin sensitivity, decreasing plasma levels of risk factors in c-SCI subjects.

Topics: Absorptiometry, Photon; Adult; Body Composition; Body Mass Index; C-Reactive Protein; Cervical Vertebrae; Exercise; Humans; Insulin Resistance; Leptin; Male; Spinal Cord Injuries

Spinal cord injury is a major cause of long-term disability and has no current clinically accepted treatment. Leptin, an adipocyte-derived hormone, is best known as a regulator of food intake and energy expenditure. Interestingly, several studies have demonstrated that leptin has significant effects on proliferation and cell survival in different neuropathologies. Here, we sought to evaluate the role of leptin after spinal cord injury.. Based on its proposed neuroprotective role, we have evaluated the effects of a single, acute intraparenchymal injection of leptin in a clinically relevant animal model of spinal cord injury. As determined by quantitative Real Time-PCR, endogenous leptin and the long isoform of the leptin receptor genes show time-dependent variations in their expression in the healthy and injured adult spinal cord. Immunohistochemical analysis of post-injury tissue showed the long isoform of the leptin receptor expression in oligodendrocytes and, to a lesser extent, in astrocytes, microglia/macrophages and neurons. Moreover, leptin administered after spinal cord injury increased the expression of neuroprotective genes, reduced caspase-3 activity and decreased the expression of pro-inflammatory molecules. In addition, histological analysis performed at the completion of the study showed that leptin treatment reduced microglial reactivity and increased caudal myelin preservation, but it did not modulate astroglial reactivity. Consequently, leptin improved the recovery of sensory and locomotor functioning.. Our data suggest that leptin has a prominent neuroprotective and anti-inflammatory role in spinal cord damage and highlights leptin as a promising therapeutic agent.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Gene Expression Profiling; Inflammation; Leptin; Locomotion; Macrophages; Male; Microglia; Neuralgia; Neurons; Neuroprotective Agents; Oligodendroglia; Peroxisome Proliferator-Activated Receptors; Rats; Rats, Wistar; Receptors, Leptin; Spinal Cord; Spinal Cord Injuries; Transcription, Genetic; Treatment Outcome; Up-Regulation

Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions.

Topics: Adipokines; Aging; Angiopoietin-Like Protein 4; Angiopoietins; Animals; eIF-2 Kinase; Eukaryotic Initiation Factor-2; Female; Gene Expression Regulation; Hypothalamus; Inflammation; Leptin; Membrane Proteins; Mice; Mice, Inbred C57BL; Protein Serine-Threonine Kinases; Receptors, Leptin; Resistin; Signal Transduction; Spinal Cord Injuries; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

Few studies have reported a relationship between leptin induced by spinal cord injury (SCI) and healing bone tissue.. To observe serum and callus leptin expression within the setting of fracture and traumatic SCI.. Seventy-two male Sprague Dawley rats were randomized equally into four groups: control, SCI group, fracture group, and fracture/SCI group. Rats were sacrificed at 7, 14, 21, and 28 days post-fracture/SCI. Serum leptin was detected using radioimmunoassay at 1, 7, 14, 21, and 28 days, and callus formation was measured radiologically at 14, 21, and 28 days. Callus leptin was analyzed by means of immunohistochemistry.. Serum leptin in the fracture group, SCI group, and combined fracture/SCI group were all significantly increased compared to control group at the 1, 7, 14, and 2-day time points (P < 0.05). Serum leptin in the combined fracture/SCI group was significantly higher than in the fracture group at 7, 14, and 21 days (P < 0.05), and higher than in SCI groups at 14 and 21days after operation (P < 0.05). The percentage of leptin-positive cells in the fracture/SCI callus, and callus volume was significantly higher than in the fracture-only group (P < 0.001).. Overall, elevated leptin expression was demonstrated within healing bone especially in the 21 days of a rat model combining fracture and SCI. A close association exists between leptin levels and the degree of callus formation in fractures.

Topics: Animals; Disease Models, Animal; Femoral Fractures; Leptin; Male; Microscopy, Electron, Transmission; Muscle, Skeletal; Radioimmunoassay; Random Allocation; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Statistics as Topic; Time Factors

To investigate the effects of exercise training with a functional electrical stimulation (FES) rowing machine on insulin resistance, plasma leptin levels, and body composition in people with spinal cord injury (SCI).. Experimental study.. A fitness and research center for people with disabilities.. Healthy male participants with paraplegia (N=6) participated in the study (mean age, 48.6±6y; mean weight, 70.06±3.28kg; injury levels between T4-5 and T10).. Twelve weeks of FES-rowing exercise training 3 to 4 times a week (600-800kcal).. Peak oxygen consumption, plasma leptin, insulin, and glucose levels, insulin sensitivity, body composition.. Twelve weeks of FES-rowing training improved aerobic fitness significantly (P=.048). In addition, plasma glucose and leptin levels were significantly decreased after exercise training by 10% and 28% (P<.028), respectively. A trend toward fat mass reduction was seen in 4 of the 6 subjects; this change did not reach statistical significance (P=.08).. A 12-week training program that included FES rowing improved aerobic fitness and fasting glucose and leptin levels in the absence of significant change to body composition, fasting insulin levels, or calculated insulin sensitivity in people with SCI.

Topics: Blood Glucose; Body Composition; Electric Stimulation Therapy; Exercise Therapy; Humans; Insulin; Leptin; Male; Middle Aged; Oxygen Consumption; Physical Fitness; Spinal Cord Injuries; Statistics, Nonparametric; Treatment Outcome

Spinal cord injury influences many hormones that are known to be involved in the modulation of neurotrophic, neurogenic, and neuroprotective events. Recent studies showed that leptin could be neuroprotective, enhancing neuronal survival in vitro and in vivo. The objective of this study was to evaluate the pattern of the serum leptin levels in rats during acute traumatic SCI.. Forty male Sprague-Dawley rats were divided randomly into 4 groups. In the control group, neither laminectomy nor SCI was performed; only laminectomy was performed without SCI in the sham group. In the cervical and thoracic spinal trauma groups, laminectomies were performed following the same trauma procedure. Blood samples were drawn 2, 6, 12, and 24 hours after the procedures and assayed immediately.. In the first 2 hours, levels of leptin were similar in control and sham-operated groups and higher in neurotrauma groups (P < 0.05). At the sixth hour, leptin levels increased in the sham-operated group, decreased in the neurotrauma groups (P < 0.05), and did not change in the control group (P > 0.05). At the 12th hour, the levels of leptin increased in all groups (P > 0.05). At the 24th hour, they decreased in the control, sham-operated, and cervical groups (P < 0.05); levels did not change in the thoracic group (P > 0.05). The decrease was higher in the control group than in the other groups (P < 0.05).. Activation of endogenous leptin secretion started immediately after the SCI. The level of neurologic lesion (either cervical or thoracic regions) affected the levels of serum leptin differently, but with the exception of the first 12-hour period, this difference did not reach a statistically significant level.

Topics: Analysis of Variance; Animals; Disease Models, Animal; Laminectomy; Leptin; Male; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Time Factors

Cross-sectional comparison.. The mortality rate is higher in individuals with spinal cord injury (SCI), and one major cause is cardiovascular disease (CVD). In the general population, the metabolic syndrome (MetS) is associated with an increased risk of CVD, and abdominal obesity is a major feature. Adipokines, secreted by adipose tissue, contribute to obesity-linked metabolic diseases. The aim of this study is to evaluate the prevalence of MetS, the components of this syndrome, especially body composition, and the relations between adipokines and body composition, in SCI individuals.. Kanagawa Rehabilitation Hospital, Kanagawa, Japan.. Forty-four male SCI individuals (57+/-13 years and 28 paraplegia) and age-matched able-bodied controls were studied. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) and anthropometry (waist circumference). The visceral fat area (VFA) was measured by computed tomography (CT). Plasma adipokine levels, including that of leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1), were measured.. Overall, 43% of SCI individuals met the criteria for MetS. Total and regional fat mass (FM), as well as VFA, were higher, whereas total and regional lean mass, except for arm, were lower than able-bodied controls. In the SCI, leptin and PAI-1 levels were positively associated and adiponectin levels were negatively associated with waist circumference, VFA and trunk FM. In multiple regression models, only leptin level was independently associated with waist circumference, VFA and trunk FM.. SCI individuals were predisposed to excessive abdominal obesity, and higher leptin levels were strongly associated with higher prevalence of abdominal obesity in this population.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Aged; Aged, 80 and over; Anthropometry; Body Composition; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Chronic Disease; Humans; Intra-Abdominal Fat; Leptin; Male; Metabolic Diseases; Middle Aged; Obesity; Spinal Cord Injuries; Tomography, X-Ray Computed

The inability to maintain body weight within prescribed ranges occurs in a significant portion of the human spinal cord injury (SCI) population. Using a rodent model of long-term high thoracic (spinal level T3) spinal cord transection (TX), we aimed to identify derangements in body weight, body composition, plasma insulin, glucose tolerance, and metabolic function, as measured by uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT). Sixteen weeks after SCI, body weights of injured female rats stabilized and were significantly lower than surgical control animals. At the same time point, SCI rats had a significantly lower whole body fat:lean tissue mass ratio than controls, as measured indirectly by NMR. Despite lower body weight and fat mass, the cumulative consumption of standard laboratory chow (4.0 kcal/g) and mean energy intake (kcal.day(-1).100 g body wt(-1)) of chronic SCI rats was significantly more than controls. Glucose tolerance tests indicated a significant enhancement in glucose handling in 16-wk SCI rats, which were coupled with lower serum insulin levels. The post mortem weight of gonadal and retroperitoneal fat pads was significantly reduced after SCI and IBAT displayed significantly lower real-time PCR expression of UCP1 mRNA. The reduced fat mass and IBAT UCP1 mRNA expression are contraindicative of the cumulative caloric intake by the SCI rats. The prolonged postinjury loss of body weight, including fat mass, is not due to hypophagia but possibly to permanent changes in gastrointestinal transit and absorption, as well as whole body homeostatic mechanisms.

Topics: Adipose Tissue; Animals; Biomarkers; Body Composition; Body Weight; Chronic Disease; Diet; Energy Intake; Female; Glucose; Glucose Tolerance Test; Insulin; Ion Channels; Leptin; Mitochondrial Proteins; Motor Activity; Organ Size; Rats; Rats, Wistar; RNA; Spinal Cord Injuries; Thermogenesis; Uncoupling Protein 1

To measure serum levels of adiponectin, ghrelin, and leptin in men with spinal cord injury (SCI) and to investigate possible correlations between these serum levels and various factors, such as body mass index (BMI), age, injury level, and duration of injury.. Cross-sectional.. A university hospital that is a tertiary referral center.. Eighty-nine men with traumatic neurologically complete SCI (30 with tetraplegia, 59 with paraplegia) and 37 age- and BMI-matched male controls. Subjects with SCI were injured at the mean age +/- standard error of 28.5+/-1.0 years (range, 14.7-59.1 y) and the mean injury duration was 10.8+/-0.7 years (range, 1.1-27.7 y).. Not applicable.. Serum levels of adiponectin, ghrelin, and leptin and BMI.. Serum leptin levels in subjects with SCI (mean, 7.0+/-0.5 mg/mL) [corrected] were significantly higher than those in able-bodied controls (mean, 4.7+/-0.6 mg/mL) [corrected] (P<.01). The group with tetraplegia had higher serum leptin levels than the group with paraplegia, but this did not reach a statistically significant level (8.2+/-1.1 ng/mL vs 6.4+/-0.5 mg/mL [corrected] P=.097). There were significant differences in serum leptin levels among the 3 groups by 1-way analysis of variance (P=.008). Serum adiponectin levels in subjects with SCI (7.1+/-0.5 mg/mL) [corrected] were higher than those in able-bodied controls (5.6+/-0.5 mg/mL) [corrected] but this was not statistically significant (P=.08). In contrast, serum levels of ghrelin in subjects with SCI (302.0+/-17.5 pg/mL) were similar to those in the controls (264.0+/-27.0 pg/mL) (P=.24). Serum leptin levels correlated positively with BMI (SCI, r=.698, P<.001; controls, r=.782, P<.001), whereas serum adiponectin (SCI, r=-.527, P<.001; controls, r=-.315, P=.057) and ghrelin (SCI, r=-.368, P<.001; controls, r=-.447, P=.006) levels correlated negatively with the BMI in both subjects with SCI and controls.. Men with SCI have significantly higher serum leptin levels than able-bodied controls, and serum leptin levels correlated with the degree of neurologic deficit. Men with SCI had a tendency toward higher serum adiponectin level than able-bodied controls. Serum levels of ghrelin in men with SCI were similar to those of controls.

Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Fasting; Ghrelin; Humans; Leptin; Linear Models; Male; Middle Aged; Paraplegia; Peptide Hormones; Quadriplegia; Regression Analysis; Spinal Cord Injuries

Compared with able-bodied (AB), people with spinal cord injury (SCI) have a 3- to 5-fold higher risk of developing type 2 diabetes mellitus, which may be associated with increased fat mass. Evidence suggests that leptin regulates body adiposity through the sympathetic nervous system, which is impaired in people with high lesion SCI. The purpose of this study was to determine the relationship among leptin levels, body composition, and resting metabolic rate (RMR) in people with high lesion SCI and body mass index-, weight-, height-, and waist circumference-matched AB subjects. Fourteen subjects (seven SCI and seven AB) participated in the study. After an overnight fast, various hormones, glucose, and RMR were measured. There was no significant difference in plasma glucose, insulin, GH, cortisol, and glucagon levels between the two groups. The SCI group had 105% higher plasma leptin levels than the AB group (P < 0.05). Plasma leptin levels correlated with body mass index (SCI: r = 0.80; P = 0.028; AB: r = 0.79; P = 0.035) and fat mass (SCI: r = 0.95; P = 0.001; AB: r = 78; P = 0.038) in both groups. The plasma leptin level correlated with the absolute RMR (SCI: r = 0.15; P = 0.75; AB: r = 0.99; P < 0.006) and the RMR per unit fat-free mass (SCI: r = -0.70; P < 0.08; AB: r = 0.845; P < 0.017) in the AB group, but not in the SCI group. The absolute RMR was significantly reduced in the SCI group compared with the AB group, but there was no difference in the relative RMR between the groups. In conclusion, the SCI group has a significantly higher plasma leptin level than the AB group. The absolute and relative RMR correlated with leptin only in the AB group.

Topics: Adult; Body Composition; Hormones; Humans; Leptin; Male; Reference Values; Rest; Spinal Cord Injuries; Sympathetic Nervous System

We studied plasma leptin levels in six people with high-lesion spinal cord injury [SCI; body mass index (BMI) 25.9 +/- 1.5 kg/m(2), age 37 +/- 3.0 yr] and six able-bodied (AB) controls (BMI 29.1 +/- 1.9 kg/m(2), age 35 +/- 3.5 yr) before and after 12, 24, and 36 h of fasting. The plasma leptin levels significantly decreased during 36 h fasting by 48.8 +/- 4.5% (pre: 11.3 +/- 2.3, post: 6.2 +/- 1.5 ng/ml) and 38.6 +/- 7.9% (pre: 7.6 +/- 5.0, post: 4.2 +/- 1.0 ng/ml) in SCI and AB, respectively. Plasma leptin started to decrease at 24 h of fasting in the SCI group, whereas plasma leptin started to decrease at 12 h of fasting in the AB group. The current study demonstrated that plasma leptin decreased with fasting in both SCI and AB groups, with the leptin decrease being delayed in the SCI group. The delayed leptin response to fasting in the SCI group may be because of increased fat mass (%body fat, SCI: 33.8 +/- 3.0, AB: 24.1 +/- 2.9) and sympathetic nervous system dysfunction.

Topics: Adult; Basal Metabolism; Body Composition; Cervical Vertebrae; Fasting; Humans; Leptin; Male; Reference Values; Spinal Cord Injuries; Sympathetic Nervous System; Time Factors

To investigate the relations among serum leptin, body mass index (BMI), and various hormone levels in men with spinal cord injury (SCI).. Cross-sectional.. University hospital that is a tertiary referral center.. Forty-seven men with traumatic neurologically complete SCI and 47 age- and BMI-matched male controls.. Baseline levels of various hormones were measured in subjects with SCI. Serum leptin and cortisol levels and BMI were measured in both groups.. Serum leptin was significantly higher in the group with SCI than in the control group. A linear relation was found between serum leptin and BMI in both groups separately. A polynomial relation was found between serum leptin level and BMI in the group with SCI. A "J" phenomenon is noted at the lowest BMI. Serum cortisol correlated significantly with serum leptin level in the group with SCI.. Sympathetic denervation, peripheral nerve palsy, recurrent infections, and possible central neurotransmitter alterations after SCI may contribute to the elevation of serum leptin level in men with SCI.

Topics: Adult; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Hormones; Humans; Hydrocortisone; Leptin; Linear Models; Male; Middle Aged; Spinal Cord Injuries; Statistics, Nonparametric; Taiwan

We addressed the relationship between plasma leptin and body mass index in 48 able-bodied male controls and 34 male subjects with spinal cord injury, as well as the association between plasma leptin with body fat by dual energy x-ray absorptiometry in those with spinal cord injury. In subjects with spinal cord injury, the effect of an oral glucose tolerance test and the relationship of the serum lipid profile with plasma leptin levels were determined. Body mass index was not significantly different between the spinal cord injury and control groups. Plasma leptin was significantly higher in the group with spinal cord injury than in the control group (12.7 +/- 1.7 vs. 7.6 +/- 0.9 ng/ml, p < 0.005). A linear relationship was found between plasma leptin and body mass index in both groups separately (spinal cord injury: r = 0.59, p < 0.0002; control: r = 0.67, p < 0.0001). In those with SCI, a polynomial relationship was evident between plasma leptin and percent fat (r = 0.82, p < 0.0001). After an oral glucose load, plasma insulin levels and serum glucose concentrations were not related to plasma leptin levels. Serum triglycerides were found to be weakly correlated with plasma leptin levels (r = 0.35, p < 0.05). The higher plasma leptin levels in the group with spinal cord injury compared with the control group was probably due to a relatively increased percentage of adiposity in those with spinal cord injury.

Topics: Absorptiometry, Photon; Adipose Tissue; Body Composition; Body Mass Index; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Leptin; Lipids; Male; Proteins; Spinal Cord Injuries; Triglycerides