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      Role of adipocytokines in the pathophysiology of migraine: A cross-sectional study

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          Abstract

          Background

          Obesity is a risk factor for migraine and headache chronification. Adipocytokines may be involved in this correlation.

          Objective

          To relate serum adipocytokine levels to clinical and biochemical parameters associated with migraine.

          Methods

          We measured levels of leptin, adiponectin and other inflammatory (interleukin 6, interleukin 10, tumor necrosis factor α, high sensitivity C-reactive protein) and endothelial (pentraxin 3, soluble TNF-like weak inducer of apoptosis) molecules potentially related to migraine pathophysiology in a group of migraine patients (IHS 2013) and healthy controls.

          Results

          One hundred and eleven patients (mean age 39.7 years, 93% female) and 24 healthy controls (mean age 35.9 years, 90% female) were included. Fifty-six patients were diagnosed with episodic migraine (mean age 35.1 years, 98.2% female) and 55 patients with chronic migraine (mean age 44.4 years, 89.5% female). Leptin serum levels (15.2 ng/mL, SD = 10.5 vs . 3.1 ng/mL, SD = 0.9; p < 0.001) and adiponectin serum levels (72.3 µg/mL, SD = 38.5 vs . 37.7 µg/mL, SD = 16.9; p < 0.001) were significantly increased in migraine patients. Leptin serum levels (15.5 ng/mL, SD = 9.7 vs . 10.8 ng/mL, SD = 6.0; p < 0.001) and adiponectin serum levels (65.8 µg/mL, SD = 42.9 vs . 33.2 µg/mL, SD = 31.0; p < 0.001) were significantly higher in chronic compared to episodic migraine patients. We found a positive correlation between leptin levels and inflammatory biomarkers: IL6 (r = 0.498; p < 0.001), TNF-α (r = 0.389; p < 0.001), and hs-CRP (r = 0.422; p < 0.001).

          Conclusions

          Leptin and adiponectin are increased in migraineurs. There is a correlation between adipocytokine levels and other inflammation-related molecules. This suggests a potential role of adipocytokines in migraine pathophysiology and chronification.

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          Most cited references36

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          The metabolic syndrome and adipocytokines.

          Visceral fat accumulation has been shown to play crucial roles in the development of cardiovascular disease as well as the development of obesity-related disorders such as diabetes mellitus, hyperlipidemia and hypertension and the so-called metabolic syndrome. Given these clinical findings, adipocytes functions have been intensively investigated in the past 10 years, and have been revealed to act as endocrine cells that have been termed adipocytokines, which secrete various bioactive substances. Among adipocytokines, tumor necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin binding epidermal growth factor-like growth factor are produced in adipocytes as well as other organs, and may contribute to the development of vascular diseases. Visfatin has been identified as a visceral-fat-specific protein that might be involved in the development of obesity-related diseases, such as diabetes mellitus and cardiovascular disease. On the contrary to these adipocytokines, adiponectin, an adipose-tissue-specific, collagen-like protein, has been noted as an important antiatherogenic and antidiabetic protein, or as an anti-inflammatory protein. The functions of adipocytokine secretion might be regulated dynamically by nutritional state. Visceral fat accumulation causes dysregulation of adipocyte functions, including oversecretion of tumor necrosis factor-alpha, plasminogen activator inhibitor type 1 and heparin binding epidermal growth factor-like growth and hyposecretion of adiponectin, which results in the development of a variety of metabolic and circulatory diseases. In this review, the importance of adipocytokines, especially focusing on adiponectin is discussed with respect to cardiovascular diseases.
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            Obesity and migraine: a population study.

            To assess the influence of body mass index (BMI) on the prevalence, attack frequency, and clinical features of migraine. In a population-based telephone interview study, the authors gathered information on headache, height, and weight. The 30,215 participants were divided into five categories, based on BMI: 1, underweight ( or = 35). Migraine prevalence and modeled headache features were assessed as a function of BMI, adjusting by covariates (age, sex, marital status, income, medical treatment, depression). Subjects were predominantly female (65% female) and in middle life (mean age 38.4). BMI group was not associated with the prevalence of migraine, but was associated with the frequency of headache attacks. In the normal weight group, 4.4% had 10 to 15 headache days per month, increasing to 5.8% of the overweight (odds ratio [OR] = 1.3), 13.6% of the obese (OR = 2.9), and 20.7% of the morbidly obese (OR = 5.7). The proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (OR = 1.9). Similar significant associations were demonstrated with BMI category for disability, photophobia, and phonophobia. Though migraine prevalence is not associated with body mass index, attack frequency, severity, and clinical features of migraine increase with body mass index group.
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              Adipose tissue as an endocrine and paracrine organ

              The discovery of leptin has imparted great impetus to adipose tissue research by demonstrating a more active role for the adipocyte in energy regulation. Besides leptin, however, the adipose tissue also secretes a large number other signals. Cytokine signals, TNFalpha and IL-6, and components of the alternative pathway of complement influence peripheral fuel storage, mobilization and combustion, as well as energy homeostasis. In addition to the acute regulation of fuel metabolism, adipose tissue also influences steroid conversion and sexual maturation. In this way, adipose tissue is an active endocrine organ, influencing many aspects of fuel metabolism through a network of local and systemic signals, which interact with the established neuroendocrine regulators of adipose tissue. Thus, insulin, catecholamines and anterior pituitary endocrine axes interact at multiple levels with both cytokines and leptin. It may be proposed that the existence of this network of adipose tissue signalling pathways, arranged in an hierarchical fashion, constitutes a metabolic repertoire which enables the organism to adapt to a range of different metabolic challenges, including starvation, reproduction, times of physical activity, stress and infection, as well as short periods of gross energy excess. However, the occurrence of more prolonged periods of energy surplus, leading to obesity, is an unusual state in evolutionary terms, and the adipose tissue signalling repertoire, although sophisticated, adapts poorly to these conditions. Rather, the responses of the adipose tissue endocrine network to obesity are maladaptive, and lay the foundations of metabolic disease.
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                Author and article information

                Journal
                Cephalalgia
                Cephalalgia
                SAGE Publications
                0333-1024
                1468-2982
                April 2018
                July 05 2017
                April 2018
                : 38
                : 5
                : 904-911
                Affiliations
                [1 ]Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain
                [2 ]Clinical Neurosciences Research Laboratory, University of Santiago de Compostela, Santiago de Compostela, Spain
                [3 ]Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain
                Article
                10.1177/0333102417720213
                365a3f80-841b-4d85-a92a-10ac12623cd3
                © 2018

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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