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Journal of Lipid Research, Vol. 48, 1655-1672, August 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology
Thematic Review |
Department of Biology, Neurobiology and Behavior Program, Georgia State University, Atlanta, GA 30302-4010
Published, JLR Papers in Press, April 25, 2007.
1 To whom correspondence should be addressed. e-mail: bartness{at}gsu.edu
During our study of the reversal of seasonal obesity in Siberian hamsters, we found an interaction between receptors for the pineal hormone melatonin and the sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT). This ultimately led us and others to conclude that the SNS innervation of WAT is the primary initiator of lipid mobilization in these as well as other animals, including humans. There is strong neurochemical (norepinephrine turnover), neuroanatomical (viral tract tracing), and functional (sympathetic denervation-induced blockade of lipolysis) evidence for the role of the SNS in lipid mobilization. Recent findings suggest the presence of WAT sensory innervation based on strong neuroanatomical (viral tract tracing, immunohistochemical markers of sensory nerves) and suggestive functional (capsaicin sensory denervation-induced WAT growth) evidence, the latter implying a role in conveying adiposity information to the brain. By contrast, parasympathetic nervous system innervation of WAT is characterized by largely negative neuroanatomical evidence (viral tract tracing, immunohistochemical and biochemical markers of parasympathetic nerves). Functional evidence (intraneural stimulation and in situ microdialysis) for the role of the SNS innervation in lipid mobilization in human WAT is convincing, with some controversy regarding the level of sympathetic nerve activity in human obesity.
Supplementary key words obesity humans viral tract tracing melanocortin melatonin denervation proliferation adipocyte hamster rat mouse human
Abbreviations: BAT, brown adipose tissue; BrDU, bromodeoxyuridine; CGRP, calcitonin gene-related peptide; CNS, central nervous system; DRG, dorsal root ganglia; DWAT, dorsosubcutaneous white adipose tissue; EPI, epinephrine; EWAT, epididymal white adipose tissue; FCN, fat cell number; FCS, fat cell size; HIV, human immunodeficiency virus; HSL, hormone-sensitive lipase; HSV, herpes simplex virus; IBAT, interscapular brown adipose tissue; -ir, immunoreactivity; IWAT, inguinal white adipose tissue; LD, long day; MC4-R, melanocortin 4-receptor; MEL, melatonin; NE, norepinephrine; NETO, norepinephrine turnover; 6OHDA, 6-hydroxy-dopamine; PRV, pseudorabies virus; PSNS, parasympathetic nervous system; PVN, paraventricular nucleus; RWAT, retroperitoneal white adipose tissue; SCN, suprachiasmatic nucleus; SD, short day; SNS, sympathetic nervous system; TH, tyrosine hydroxylase; WAT, white adipose tissue
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