Increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human synovium and mouse lymph nodes in arthritis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 63; no. 11; pp. 3234 - 3242
• Main Authors: Straub, Rainer H., Lowin, Torsten, Klatt, Susanne, Wolff, Christine, Rauch, Luise
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2011; Wiley; Wiley Subscription Services, Inc
• Subjects: Adipocytes; Adipose Tissue - innervation; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adrenergic Fibers - metabolism; Adrenergic Fibers - pathology; Aged; Animals; Arthritis; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Diseases of the osteoarticular system; Female; Humans; Lymph Nodes - innervation; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Medical sciences; Mice; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Osteoarthritis - metabolism; Osteoarthritis - pathology; Rodents; Studies; Synovial Membrane - innervation; Synovial Membrane - metabolism; Synovial Membrane - pathology; Weight control; Human; Sympathetic nerve; Lymph node; Diseases of the osteoarticular system; Rodentia; Rheumatology; Arthritis; Density; Vertebrata; Mammalia; Mouse; Synovial membrane; Animal; Fat; Nerve fiber
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.30516

Objective To investigate the density of sympathetic nerve fibers in and the metabolic activation of fat tissue surrounding human synovium in rheumatoid arthritis (RA)/osteoarthritis (OA) and in the draining lymph nodes of arthritic and normal mice. Methods Using immunofluorescence and immunohistochemistry, the density of sympathetic nerve fibers and the presence of nerve repellent factors were investigated. The metabolic activation of fat tissue was estimated by the occurrence of small‐vacuole adipocytes, expression of β3‐adrenoceptors, and adipose tissue weight. Results The density of sympathetic nerve fibers was markedly increased in fat tissue surrounding RA synovium compared with that in fat tissue surrounding OA synovium. In adipose tissue adjacent to draining lymph nodes, the density of sympathetic nerve fibers was higher in arthritic mice compared with normal mice. In human synovium and mouse draining lymph nodes, the 2 sympathetic nerve repellent factors, semaphorin 3C and semaphorin 3F, were highly expressed. In arthritic compared with normal mice, the fat tissue around lymph nodes was markedly lighter, adipocytes had more fragmented lipid droplets, and fat tissue demonstrated high expression of β3‐adrenoceptors. Conclusion This study demonstrated an increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human RA synovium and the draining lymph nodes of arthritic mice. Because sympathetic neurotransmitters stimulate lipolysis, the repulsion of sympathetic nerve fibers from inflamed regions and their increased occurrence in fat tissue probably represent an adaptive program to support the proinflammatory process by releasing energy‐rich substrates.