RRC ID 37554
Author Tang L, Okamoto S, Shiuchi T, Toda C, Takagi K, Sato T, Saito K, Yokota S, Minokoshi Y.
Title Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages.
Journal Endocrinology
Abstract Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-α at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-α mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and β-adrenergic antagonist propranolol up-regulated TNF-α mRNA in both epiWAT and BAT in vivo. Signaling by the β2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-α mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-α mRNA in the stromal vascular fraction of this tissue. β-AR-deficient (β-less) mice manifested an increased plasma TNF-α concentration and increased TNF-α mRNA abundance in epiWAT and BAT. TNF-α mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and β2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and β2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS.
Volume 156(10)
Pages 3680-94
Published 2015-10-1
DOI 10.1210/EN.2015-1096
PMID 26132918
MeSH Adipose Tissue, Brown / drug effects Adipose Tissue, Brown / innervation Adipose Tissue, Brown / metabolism Adipose Tissue, White / drug effects Adipose Tissue, White / innervation Adipose Tissue, White / metabolism* Adrenergic beta-Antagonists / pharmacology Agouti-Related Protein / administration & dosage Animals Cell Line Epididymis / drug effects Epididymis / metabolism Gene Expression / drug effects Immunoblotting Inflammation Mediators / metabolism* Injections, Intraventricular Macrophages / metabolism* Male Mice, Inbred C57BL Mice, Knockout Peptide Fragments / administration & dosage Propranolol / pharmacology Receptors, Adrenergic, beta / genetics Receptors, Adrenergic, beta / metabolism Reverse Transcriptase Polymerase Chain Reaction Sympathectomy Sympathetic Nervous System / metabolism* Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism*
IF 3.934
Times Cited 16
Human and Animal Cells RAW 264(RCB0535)