Cerebrospinal fluid and plasma leptin measurements: Covariability with dopamine and cortisol in fasting humans

Leptin (OB protein) is an important signal in the regulation of energy bala nce. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an establish ed critical site of leptin function, yet little is known about leptin conce ntrations in the central nervous system relative to plasma levels, psychiat ric diagnoses, and other endocrine parameters. Therefore, using a novel ult rasensitive leptin assay, we explored relationships of human plasma and cer ebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraum atic stress disorder diagnosis, and levels of dopamine, monoamine metabolit es, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A s trong linear relation between CSF and plasma leptin levels in the am (r = 0 .63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasti ng. A strong association was found between plasma leptin and CSF dopamine l evels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implic ations for leptin transport, regulation, and its potential role in therapeu tic strategies for obesity and diabetes are discussed.