leptin and Migraine-Disorders

Migraine comorbidity with obesity is not new and studies have focused on how adipose tissue-derived substances such as adipokines might be involved in the migraine pathophysiology. Quantification of the nature and magnitude of the association between each adipokine including leptin, adiponectin and resistin with migraine pathophysiology is the objective of the current study.. Using systematic reviews and meta-analyses and standardized mean difference as effect size, the levels of three adipokines, leptin, adiponectin and resistin, have been investigated in migraineur subjects in the case-control studies.. Using random-effects models, the final analyses demonstrated the standardized mean differences of leptin, adiponectin and resistin as 0.534 (95% confidence interval, 0.169-0.898), 0.439 (95% confidence interval, 0.132-0.746) and 0.194 (95% confidence interval, -0.158-0.546), respectively. The. Based on the findings, the blood levels of leptin and adiponectin, but not resistin, of the migraineurs are associated with disease pathogenesis.

Topics: Adiponectin; Biomarkers; Case-Control Studies; Humans; Leptin; Migraine Disorders; Resistin

The high prevalence of osteoporosis, observed in multiple sclerosis (MS) patients, has been attributed to reduced mobility and or the use of disease-modifying drugs. However, MS-impaired cardiovascular autonomic nervous system (ANS) function has the potential of reducing bone mass density (BMD) by altering the expression and/or function of the neuronal, systemic, and local mediators of bone remodeling. This review describes the complex regulation of bone homeostasis with a focus on MS, providing evidence that ANS dysfunction and low BMD are intertwined with MS inflammatory and neurodegenerative processes, and with other MS-related morbidities, including depression, fatigue, and migraine. Strategies for improving ANS function could reduce the prevalence of MS osteoporosis and slow the rate of MS progression, with a significant positive impact on patients' quality of life.

Topics: Adiponectin; Autonomic Nervous System; Bone Density; Bone Remodeling; Brain; Cardiovascular System; Depression; Endocannabinoids; Fatigue; Humans; Inflammation; Leptin; Migraine Disorders; Multiple Sclerosis; Nerve Degeneration; Neuropeptide Y; Osteocalcin; Osteopontin; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Serotonin; Vitamin D

Obesity and migraine are both highly prevalent disorders in the general population, influenced by genetic and environmental risk factors. In recent studies, obesity was found to be a strong risk factor for transformed migraine and, among migraineurs, obesity was associated with frequent headaches and higher disability scores. Suggested mechanisms included: (i) obesity as a pro-inflammatory state may be associated with neurovascular inflammation in patients with migraine; (ii) elevated levels of plasma calcitonin gene-related peptide (CGRP) in obese individuals may play a role as an important post-synaptic mediator of trigeminovascular inflammation in migraine; (iii) dismodulation in the hypothalamic neuropeptide, orexin, in obese persons may be associated with increased susceptibility to neurogenic inflammation causing migraine attacks; and (iv) leptin and adiponectin can activate proinflammatory cytokine release that is involved in the pathogenesis of migraine. In addition, both conditions are associated with psychiatric co-morbidities, such as depression and anxiety, that can further increase headache frequency and disability. Therefore, the effect of obesity on migraine outcome is important. Weight and BMI should be measured and calculated in all children presenting with migraine, and weight control should be a part of the treatment.

Topics: Adiponectin; Calcitonin Gene-Related Peptide; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Migraine Disorders; Neurogenic Inflammation; Neuropeptides; Orexins; Pediatric Obesity; Risk Factors; Weight Loss

Although it has long been known that fasting or the consumption of certain foods can trigger headaches, abdominal and total body obesity have only recently been linked to migraine. Several adipocytokines appear to play an integral role in feeding and obesity--and have also been linked to pain. Among these proteins are adiponectin and leptin. The author reviews the regulation of adipose tissue and feeding and provides an in-depth examination of adiponectin and leptin and their association with migraine.

Topics: Adiponectin; Appetite; Biomarkers; Humans; Leptin; Migraine Disorders; Obesity

Migraine is a disabling neurogenic disorder characterized by recurrent headache attacks. Adipokines act as inflammatory and pain mediators that contribute to migraine pathogenesis. Leptin and adiponectin levels change in migraine patients and are associated with headache attacks. Curcumin can exert modulatory and analgesic effects on adipokines through several mechanisms, from gene expression to suppressing pain. The aim of the present study was to evaluate the effects of nano-curcumin supplementation on leptin and adiponectin gene expression, their serum levels and migraine symptoms in patients with migraine.. Forty-four episodic migraine patients enrolled in this trial were divided into two groups as nano-curcumin (80 mg/day) and placebo group, over a two-month period. At the beginning and the end of the study, the mRNA expression of leptin and adiponectin from isolated PBMCs and their serum levels were measured using real-time PCR and ELISA method, respectively. The headache frequencies, severity and duration of pain were also recorded.. The results of the present research showed that nano-curcumin can up-regulate adiponectin mRNA and increase its serum level significantly (P < 0.05). In the case of leptin, a reduction in gene expression and concentration was found in the nano-curcumin group but it was not statistically significant (P > 0.05). Nano-curcumin also significantly reduced the frequency, severity and duration of headaches (P < 0.05).. These findings indicate that nano-curcumin supplement can be considered as a promising approach to migraine management and clinical symptoms improvement.

Topics: Adipokines; Adiponectin; Curcumin; Dietary Supplements; Double-Blind Method; Gene Expression; Headache; Humans; Leptin; Migraine Disorders; RNA, Messenger

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; C-Peptide; Female; Flunarizine; Humans; Insulin; Leptin; Male; Migraine Disorders; Vasodilator Agents; Weight Gain

To evaluate the prevalence of periodontitis (CP) and its contribution to serum leptin levels in chronic migraine (CM).. In this case-control study, we included 150 subjects divided into healthy controls (n = 58) and CM patients (n = 92). Demographic, neurological, clinical data as well as full-mouth periodontal records were obtained. Serum leptin levels were measured by ELISA technique.. CP is prevalent in CM patients and when present it contributes to elevated serum leptin levels, independently of other confounding factors. Therefore, it seems that CP via leptin could be involved in the process of migraine chronification.

Topics: Adipokines; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Dental Plaque Index; Educational Status; Female; Humans; Leptin; Male; Middle Aged; Migraine Disorders; Multivariate Analysis; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Regression Analysis; Spain

Background and aims Adiponectin, leptin, and resistin are adipocyte-derived secretory factors involved in endothelial function, weight, inflammation, and insulin resistance. Recent studies suggested a role for adipokines in episodic migraine as mediators of inflammatory processes. The aim of this study was to investigate plasma concentrations of adiponectin, leptin, and resistin in patients with chronic migraine. Materials and methods Twenty-seven chronic migraineurs (20 females, 7 males; mean age 49.0 ± 9.0 yrs) and 37 healthy controls (23 females, 14 males; mean age 49.8 ± 15.0 yrs) were selected for the study. Fasting plasmatic levels of total adiponectin, leptin, and resistin were measured using ELISA kits during a pain-free period. Fasting glucose, insulin, total and HDL-cholesterol, triglycerides, and ESR were also determined. Results Serum levels of adiponectin and resistin were significantly increased in chronic migraineurs in comparison with controls ( p = 0.001 and p = 0.032, respectively). After correction for BMI, sex and age, leptin levels were significantly increased in chronic migraineurs ( p = 0.007). A positive correlation between leptin concentrations and both indices of insulin resistance and markers of inflammation was found. Discussion Our data suggest that adiponectin and resistin are altered in non-obese chronic migraineurs. Further studies are needed to elucidate the neurobiological mechanisms underlying adipokine dysfunction in migraine.

Topics: Adiponectin; Adult; Aged; Biomarkers; Female; Headache Disorders; Humans; Leptin; Male; Middle Aged; Migraine Disorders; Resistin

Topics: Analgesics, Non-Narcotic; Animals; Arcuate Nucleus of Hypothalamus; Glucagon; Hypothalamus; Insulin; Leptin; Male; MAP Kinase Signaling System; Migraine Disorders; Neural Pathways; Neurons; Pain; Rats, Sprague-Dawley; Trigeminal Nuclei

Obesity is a risk factor for episodic migraine to develop into chronic migraine; hence, it is speculated that obesity and hyperleptinemia are associated with migraine. We hypothesized that leptin is involved in the mechanisms of cortical spreading depression (CSD). Therefore, we examined whether leptin affected a rat model of CSD to clarify the relationship between leptin and migraine.. We evaluated the effect of intracerebroventricular (ICV) administration of leptin on a rat CSD model. We then examined whether once-a-day intraperitoneal administration of leptin for seven days (as a chronic hyperleptinemia model) affected rat CSD models. Finally, we induced CSD in Zucker fatty (ZF) rats, which is a well-known model of obesity.. In the parietal cortex, the percent change in cerebral blood flow and direct current (DC) potential decreased after ICV administration of leptin. A similar decrease in DC potential was observed in rats treated with intraperitoneal leptin. The number of CSDs increased significantly in rats given intraperitoneal leptin and in ZF rats.. The present study suggests that leptin is involved in the mechanisms of CSD.

Topics: Animals; Cerebral Cortex; Cerebrovascular Circulation; Cortical Spreading Depression; Disease Models, Animal; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Migraine Disorders; Obesity; Rats; Rats, Sprague-Dawley; Rats, Zucker

Topics: Adiponectin; Female; Humans; Leptin; Male; Migraine Disorders

Topics: Adiponectin; Female; Humans; Leptin; Male; Migraine Disorders

The aim of this study was to analyze the effects of obesity and leptin levels on patients with migraine, and to observe the change of leptin levels in migraineurs.. We enrolled 52 migraine patients from the Headache Clinic in Shandong Provincial Hospital into a randomized controlled trial with another 52 age-, sex-, and BMI-matched healthy subjects as controls. Leptin levels in all subjects were determined by radioimmunoassay.. Compared with the control group, the migraineurs revealed no significant change in leptin levels (P>0.05). Multivariate Logistic regression analysis showed that neither abdominal obesity nor leptin had significant impact on migraine clinical features. Total body obesity had a significant effect on the frequency (OR=4.248), duration (OR=3.167), and intensity (OR=5.225) of the headache.. Total body obesity affected headache frequency, intensity, and duration, while leptin levels did not.

Topics: Adolescent; Adult; Body Mass Index; Case-Control Studies; China; Female; Humans; Leptin; Male; Middle Aged; Migraine Disorders; Multivariate Analysis; Obesity; Obesity, Abdominal; Odds Ratio; Radioimmunoassay; Young Adult

To evaluate adiponectin and leptin levels in older men and women with migraine.. Fasting total and high molecular weight (HMW) adiponectin and leptin levels were evaluated in a case-cohort study of nondiabetic older migraine and nonmigraine control participants from the ongoing, longitudinal, general population, Atherosclerosis Risk in Communities Study at visit 1 (1987-1989). A standardized headache questionnaire was completed at visit 3 (1993-1995). Logistic regression models adjusted for age, sex, race, center, body mass index, and fasting glucose were used to evaluate the association of each adipocytokine with migraine.. Of the 981 participants, the mean age at baseline was 52.8 years (SE 0.3); 131 fulfilled migraine criteria. Crude, mean total adiponectin levels were greater in men and women with migraine (8.1 µg/mL, SE 0.5) as compared to those without migraine (7.0 µg/mL, SE 0.2) (p = 0.031). After adjustments, the odds of migraine were increased by 88% with each SD increase in total adiponectin in men (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.15, 3.01; p = 0.011), but not in women (OR 1.05; 95% CI 0.80, 1.37; p = 0.728; p interaction = 0.029). Similar results were demonstrated for HMW adiponectin. Crude and adjusted leptin levels were not associated with migraine.. Although crude, total adiponectin levels were higher in older men and women with migraine than controls, after adjustments, the prevalence of migraine was significantly associated with total adiponectin only in older men, suggesting the association may be confounded or absent in older women. Leptin was not associated with migraine in older men or women.

Topics: Adiponectin; Atherosclerosis; Blood Chemical Analysis; Case-Control Studies; Female; Humans; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Migraine Disorders; Odds Ratio; Prevalence; Prospective Studies; Risk; Sex Factors; Surveys and Questionnaires

Topics: Adiponectin; Female; Humans; Leptin; Male; Migraine Disorders

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Obesity Agents; Anticonvulsants; Body Mass Index; Cytokines; Female; Fructose; Hip; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Vascular Endothelial Growth Factors; Waist Circumference; Weight Loss

Impaired insulin metabolism has been implicated in migraine. However, to date only some putative effects, especially regarding the involvement of adipocytokines and glucagon-like peptides (GLPs), have been described. The aim of the present study was to investigate adipocytokines and GLPs in non-obese female migraineurs.. Various parameters of the insulin metabolism and body measurements were determined in 84 non-obese female subjects.. We found highly significantly increased insulin levels with an odds ratio of 10.62 for migraine. Leptin and GLP-2 levels were also increased and correlated with insulin. Logistic regression analysis of leptin and GLP-2 revealed odds ratios of 3.79 and 4.26 for migraine, respectively, when comparing the lowest with the highest quartile of the test variable in the complete study cohort.. We show that non-obese female migraineurs suffer from hyperinsulinemia, which is associated with elevated leptin and GLP-2 levels. Increased leptin and GLP-2 are risk factors for migraine. Our data suggest that migraine is associated with a higher risk for insulin resistance and its clinical consequences.

Topics: Adult; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Glucagon-Like Peptide 2; Humans; Hyperinsulinism; Leptin; Migraine Disorders; Risk Factors

The study objective was to evaluate levels of the cytokines tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 and of leptin, and then to determine the relationship between these levels and clinical responses in children with migraine after prophylactic therapy with one of four drugs. In all, 77 children who needed prophylactic drugs were treated with cyproheptadine, amitriptyline, propranolol, or flunarizine. Serum levels of the cytokines and leptin were measured before and 4 months after the treatment. Results were compared by drug for headache frequency, severity, and duration, the PedMIDAS score, and levels of each cytokine and of leptin. Each of the four drugs not only decreased the frequency and duration but also the severity of headache, and the PedMIDAS score. None of the drugs was found to be superior to others in terms of reduction in cytokine levels (P > 0.05). Both cyproheptadine and flunarizine (but not amitriptyline and propranolol) caused an increase in leptin levels (P < 0.05). These data suggest that cytokine levels are related to clinical responses, and might help in objective evaluation of clinical response in migraine. To our knowledge, the present study is the first trial to compare the effects of prophylactic drugs, cytokine levels, and leptin levels in children with migraine.

Topics: Adolescent; Amitriptyline; Central Nervous System Agents; Child; Cyproheptadine; Cytokines; Female; Flunarizine; Humans; Interleukin-1beta; Interleukin-6; Leptin; Male; Migraine Disorders; Propranolol; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Obesity has been shown to be a risk factor for transformation of episodic migraine to chronic form, and adipocytokines have been implicated to modulate some of the cytokins such as interleukin-6 and tumor necrosis factor, which also act in the neurogenic inflammation in migraine. The aim of the study was to assess leptin levels, one of the adipocytokines, in headache-free period of migraine patients and investigate its relation to vascular risk factors.. Sixty-one patients with episodic migraine headaches and 64 control subjects were enrolled in the study. Demographic data and anthropometric measurements were obtained from all participants; body mass index and fat mass values were calculated. Glucose and lipid parameters were measured by oxidase technique and cholesterol esterase enzymatic assays, and leptin levels were measured by ELISA in serum samples obtained after an overnight fasting.. Leptin levels were found significantly lower in migraineurs than controls (40.1 +/- 21.2 ng/mL, 48.5 +/- 24.5 ng/mL; P < .05). Although body mass index did not differ between 2 groups, fat mass, and fat percentages were significantly lower in migraine patients (19.4 +/- 8.8 kg, 26.0 +/- 8.7 kg; P < .001 and 28 +/- 9%, 34 +/- 5%; P < .001, respectively).. Migraine patients have low leptin levels and fat mass which may be related to the pathogenesis of migraine. The importance and impact of our findings on the prevalence, characteristics, and treatment of migraine needs to be investigated in further detailed studies.

Topics: Adipose Tissue; Adult; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Migraine Disorders; Obesity; Young Adult