Adipokines and Migraine: A Systematic Review

Abstract

Background: Migraine is comorbid with obesity. Recent research suggests an association between migraine and adipocytokines, proteins that are predominantly secreted from adipose tissue and which participate in energy homeostasis and inflammatory processes.

Objectives: In this review, we first briefly discuss the association between migraine and obesity and the importance of adipose tissue as a neuroendocrine organ. We then present a systematic review of the extant literature evaluating circulating levels of adiponectin and leptin in those with migraine.

Methods: A search of the PubMed database was conducted using the keywords "migraine," "adiponectin," and "leptin." In addition reference lists of relevant articles were reviewed for possible inclusion. English language studies published between 2005 and 2015 evaluating circulating blood concentration of adiponectin or leptin in those with migraine were included.

Conclusions: While the existing data are suggestive that adipokines may be associated with migraine, substantial study design differences and conflicting results limit definitive conclusions. Future research utilizing carefully considered designs and methodology is warranted. In particular careful and systematic characterization of pain states at the time of samples, as well as systematic consideration of demographic (e.g., age, sex) and other vital covariates (e.g., obesity status, lipids) are needed to determine if adipokines play a role in migraine pathophysiology and if any adipokine represents a viable, novel migraine biomarker, or drug target.

Keywords: adipokines; adiponectin; leptin; migraine; obesity.

Fig. 1

The prevalence of migraine/severe headache in obese and non-obese women and men by age. In the National Health and Examination Survey, the prevalence of migraine and severe headaches was increased in obese compared to non-obese adults under 55 years of age and not in those older than 55. ***P ≤ .001; **P ≤ .01; *P ≤ .05. Adapted with permission from Headache.

Fig. 2

Sexual dimorphism of adiponectin (A) and leptin (B). (A) Serum levels of the adiponectin multimers from women and age- and body mass index-matched men were evaluated using an enzyme immunoassay. Adapted from Ref. . (B) Serum leptin levels from women and men were evaluated by enzyme immunoassay. Figure data from Ref. . *P < .05; **P < .01.

Fig. 3

PRISMA flow diagram of manuscripts evaluating blood levels of adiponectin in those with migraine.

Fig. 4

Serum total adiponectin (T-ADP) and ADP multimers in non-diabetic, normotensive reproductive-aged (<50) women with episodic migraine (EM, n = 13), chronic daily headache (CDH) with either chronic or transformed migraine (n = 12), and non-headache controls (n = 12). After adjusting for WHR, levels varied significantly across the three headache groups (P = .024). Adapted from Ref. .

Fig. 5

PRISMA flow diagram of manuscripts evaluating blood levels of leptin in those with migraine.