biomarkers of endocannabinoid system activation in severe obesity神经系统活动的生物标志物在严重肥胖.pdf

Biomarkers of Endocannabinoid System Activation in Severe Obesity 1 1 3 1,3¤ 2 Jack C. Sipe *, T. Michael Scott , Sarah Murray , Olivier Harismendy , Gabriel M. Simon , Benjamin F. Cravatt2, Jill Waalen1 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America, 2 Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America, 3 Scripps Genomic Medicine-Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, California, United States of America Abstract Background: Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in the regulation of body weight. The main research question here was whether quantitative measurement of plasma endocannabinoids, anandamide, and related N-acylethanolamines (NAEs), combined with genotyping for mutations in fatty acid amide hydrolase (FAAH) would identify circulating biomarkers of ECS activation in severe obesity. Methodology/Principal Findings: Plasma samples were obtained from 96 severely obese subjects with body mass index (BMI) of $40 kg/m2 2 , and 48 normal weight subjects with BMI of #26 kg/m . Triple-quadrupole mass spectroscopy methods were used to measure plasma ECS analogs. Subjects were genotyped for human FAAH gene mutations. The principal analysis focus